@article {pmid36692278, year = {2022}, author = {Forterre, P and Gaïa, M}, title = {[Viruses and the evolution of modern eukaryotic cells].}, journal = {Medecine sciences : M/S}, volume = {38}, number = {12}, pages = {990-998}, doi = {10.1051/medsci/2022164}, pmid = {36692278}, issn = {1958-5381}, abstract = {It is now well accepted that viruses have played an important role in the evolution of modern eukaryotes. In this review, we suggest that interactions between ancient eukaryoviruses and proto-eukaryotes also played a major role in eukaryogenesis. We discuss phylogenetic analyses that highlight the viral origin of several key proteins in the molecular biology of eukaryotes. We also discuss recent observations that, by analogy, could suggest a viral origin of the cellular nucleus. Finally, we hypothesize that mechanisms of cell differentiation in multicellular organisms might have originated from mechanisms implemented by viruses to transform infected cells into virocells.}, } @article {pmid36688393, year = {2023}, author = {Townsend, C and Ferraro, JV and Habecker, H and Flinn, MV}, title = {Human cooperation and evolutionary transitions in individuality.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {378}, number = {1872}, pages = {20210414}, doi = {10.1098/rstb.2021.0414}, pmid = {36688393}, issn = {1471-2970}, mesh = {Humans ; *Biological Evolution ; *Social Behavior ; Adaptation, Physiological ; Communication ; }, abstract = {A major evolutionary transition in individuality involves the formation of a cooperative group and the transformation of that group into an evolutionary entity. Human cooperation shares principles with those of multicellular organisms that have undergone transitions in individuality: division of labour, communication, and fitness interdependence. After the split from the last common ancestor of hominoids, early hominins adapted to an increasingly terrestrial niche for several million years. We posit that new challenges in this niche set in motion a positive feedback loop in selection pressure for cooperation that ratcheted coevolutionary changes in sociality, communication, brains, cognition, kin relations and technology, eventually resulting in egalitarian societies with suppressed competition and rapid cumulative culture. The increasing pace of information innovation and transmission became a key aspect of the evolutionary niche that enabled humans to become formidable cooperators with explosive population growth, the ability to cooperate and compete in groups of millions, and emergent social norms, e.g. private property. Despite considerable fitness interdependence, the rise of private property, in concert with population explosion and socioeconomic inequality, subverts potential transition of human groups into evolutionary entities due to resurgence of latent competition and conflict. This article is part of the theme issue 'Human socio-cultural evolution in light of evolutionary transitions'.}, } @article {pmid36688387, year = {2023}, author = {Davison, DR and Michod, RE}, title = {Steps to individuality in biology and culture.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {378}, number = {1872}, pages = {20210407}, doi = {10.1098/rstb.2021.0407}, pmid = {36688387}, issn = {1471-2970}, mesh = {Animals ; Humans ; Biological Evolution ; *Hominidae ; *Cultural Evolution ; Biology ; }, abstract = {Did human culture arise through an evolutionary transition in individuality (ETI)? To address this question, we examine the steps of biological ETIs to see how they could apply to the evolution of human culture. For concreteness, we illustrate the ETI stages using a well-studied example, the evolution of multicellularity in the volvocine algae. We then consider how those stages could apply to a cultural transition involving integrated groups of cultural traditions and the hominins that create and transmit traditions. We focus primarily on the early Pleistocene and examine hominin carnivory and the cultural change from Oldowan to Acheulean technology. We use Pan behaviour as an outgroup comparison. We summarize the important similarities and differences we find between ETI stages in the biological and cultural realms. As we are not cultural anthropologists, we may overlook or be mistaken in the processes we associate with each step. We hope that by clearly describing these steps to individuality and illustrating them with cultural principles and processes, other researchers may build upon our initial exercise. Our analysis supports the hypothesis that human culture has undergone an ETI beginning with a Pan-like ancestor, continuing during the Pleistocene, and culminating in modern human culture. This article is part of the theme issue 'Human socio-cultural evolution in light of evolutionary transitions'.}, } @article {pmid36529400, year = {2023}, author = {Liu, Y and Cao, M and Yan, X and Cai, X and Li, Y and Li, C and Xue, T}, title = {Genome-wide identification of gap junction (connexins and pannexins) genes in black rockfish (Sebastes schlegelii): Evolution and immune response mechanism following challenge.}, journal = {Fish & shellfish immunology}, volume = {132}, number = {}, pages = {108492}, doi = {10.1016/j.fsi.2022.108492}, pmid = {36529400}, issn = {1095-9947}, mesh = {Animals ; *Connexins/genetics ; Phylogeny ; Gap Junctions/chemistry/metabolism ; *Perciformes/metabolism ; Immunity ; }, abstract = {Cell-to-cell communication through gap junction channels is very important to coordinate the functions of cells in all multicellular biological tissues. It allows the direct exchange of ions and small molecules (including second messengers, such as Ca[2+], IP3, cyclic nucleotides, and oligonucleotides). In this study, a total of 48 members of the gap junction (GJ) protein family were identified from Sebastes schlegelii. In S. schlegelii, GJ proteins were classified into two types, connexin, and pannexin, and then connexins were divided into five subfamilies. The naming of 48 genes was verified through phylogenetic analysis and syntenic analysis. The connexin proteins contained four transmembrane fragments and two extracellular loops, the lengths of the intracellular loop and C-terminal was quite different, and the C-terminal region was highly variable after post-translational modification. PPI analysis showed that GJs interacted with tight junctions, adhesive junctions, and cell adhesions to form a complex network and participated in cell-cell junction organization, ATP binding, ion channel, voltage-gated conduction, wnt signaling pathway, Fc-γ receptor signaling pathway, and DNA replication. In addition, the S. schlegelii GJ protein was highly expressed in intestinal tissues and remarkably regulated after Edwardsiella tarda and Streptococcus iniae infection. The expression of GJs in intestinal cells of S. schlegelii was significantly regulated by LPS and poly (I:C), which was consistent with the results of intestinal tissue stimulation by pathogens. In conclusion, this study can provide valuable information for further research on the function of S. schlegelii GJ proteins.}, } @article {pmid36688394, year = {2023}, author = {McShea, DW}, title = {Four reasons for scepticism about a human major transition in social individuality.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {378}, number = {1872}, pages = {20210403}, doi = {10.1098/rstb.2021.0403}, pmid = {36688394}, issn = {1471-2970}, abstract = {The 'major transitions in evolution' are mainly about the rise of hierarchy, new individuals arising at ever higher levels of nestedness, in particular the eukaryotic cell arising from prokaryotes, multicellular individuals from solitary protists and individuated societies from multicellular individuals. Some lists include human societies as a major transition, but based on a comparison with the non-human transitions, there are reasons for scepticism. (i) The foundation of the major transitions is hierarchy, but the cross-cutting interactions in human societies undermine hierarchical structure. (ii) Natural selection operates in three modes-stability, growth and reproductive success-and only the third produces the complex adaptations seen in fully individuated higher levels. But human societies probably evolve mainly in the stability and growth modes. (iii) Highly individuated entities are marked by division of labour and commitment to morphological differentiation, but in humans differentiation is mostly behavioural and mostly reversible. (iv) As higher-level individuals arise, selection drains complexity, drains parts, from lower-level individuals. But there is little evidence of a drain in humans. In sum, a comparison with the other transitions gives reasons to doubt that human social individuation has proceeded very far, or if it has, to doubt that it is a transition of the same sort. This article is part of the theme issue 'Human socio-cultural evolution in light of evolutionary transitions'.}, } @article {pmid36325178, year = {2022}, author = {Sakai, D and Nishikawa, J and Kakiuchida, H and Hirose, E}, title = {Stack of cellular lamellae forms a silvered cortex to conceal the opaque organ in a transparent gastropod in epipelagic habitat.}, journal = {PeerJ}, volume = {10}, number = {}, pages = {e14284}, pmid = {36325178}, issn = {2167-8359}, mesh = {Animals ; *Silver ; *Gastropoda ; Cell Nucleus ; Vision, Ocular ; Light ; }, abstract = {BACKGROUND: Gelatinous zooplankton in epipelagic environments often have highly transparent bodies to avoid detection by their visual predators and prey; however, the digestive systems are often exceptionally opaque even in these organisms. In a holoplanktonic gastropod, Pterotrachea coronata, the visceral nucleus is an opaque organ located at the posterior end of its alimentary system, but this organ has a mirrored surface to conceal its internal opaque tissue.

RESULTS: Our ultrastructural observation proved that the cortex of the visceral nucleus comprised a stack of thin cellular lamellae forming a Bragg reflector, and the thickness of lamellae (0.16 µm in average) and the spaces between the lamellae (0.1 µm in average) tended to become thinner toward inner lamellae. Based on the measured values, we built virtual models of the multilamellar layer comprising 50 lamellae and spaces, and the light reflection on the models was calculated using rigorous coupled wave analysis to evaluate their properties as reflectors. Our simulation supported the idea that the layer is a reflective tissue, and the thickness of the lamella/space must be chirped to reflect sunlight as white/silver light, mostly independent of the angle of incidence.

CONCLUSIONS: In P. coronata, the cortex of the visceral nucleus comprised multicellular lamellae that form a chirped Bragg reflector. It is distinct in structure from the intracellular Bragg structures of common iridophores. This novel Bragg reflector demonstrates the diversity and convergent evolution of reflective tissue using reflectin-like proteins in Mollusca.}, } @article {pmid36655713, year = {2023}, author = {Römling, U}, title = {Is biofilm formation intrinsic to the origin of life?.}, journal = {Environmental microbiology}, volume = {25}, number = {1}, pages = {26-39}, doi = {10.1111/1462-2920.16179}, pmid = {36655713}, issn = {1462-2920}, mesh = {Humans ; *Biofilms ; }, abstract = {Biofilms are multicellular, often surface-associated, communities of autonomous cells. Their formation is the natural mode of growth of up to 80% of microorganisms living on this planet. Biofilms refractory towards antimicrobial agents and the actions of the immune system due to their tolerance against multiple environmental stresses. But how did biofilm formation arise? Here, I argue that the biofilm lifestyle has its foundation already in the fundamental, surface-triggered chemical reactions and energy preserving mechanisms that enabled the development of life on earth. Subsequently, prototypical biofilm formation has evolved and diversified concomitantly in composition, cell morphology and regulation with the expansion of prokaryotic organisms and their radiation by occupation of diverse ecological niches. This ancient origin of biofilm formation thus mirrors the harnessing environmental conditions that have been the rule rather than the exception in microbial life. The subsequent emergence of the association of microbes, including recent human pathogens, with higher organisms can be considered as the entry into a nutritional and largely stress-protecting heaven. Nevertheless, basic mechanisms of biofilm formation have surprisingly been conserved and refunctionalized to promote sustained survival in new environments.}, } @article {pmid36650459, year = {2023}, author = {Nozaki, H and Mori, F and Tanaka, Y and Matsuzaki, R and Yamashita, S and Yamaguchi, H and Kawachi, M}, title = {Cryopreservation of two species of the multicellular volvocine green algal genus Astrephomene.}, journal = {BMC microbiology}, volume = {23}, number = {1}, pages = {16}, pmid = {36650459}, issn = {1471-2180}, mesh = {*Chlorophyta/genetics ; Cryopreservation/methods ; Freezing ; Dimethylformamide ; }, abstract = {BACKGROUND: Astrephomene is an interesting green algal genus that, together with Volvox, shows convergent evolution of spheroidal multicellular bodies with somatic cells of the colonial or multicellular volvocine lineage. A recent whole-genome analysis of A. gubernaculifera resolved the molecular-genetic basis of such convergent evolution, and two species of Astrephomene were described. However, maintenance of culture strains of Astrephomene requires rapid inoculation of living cultures, and cryopreserved culture strains have not been established in public culture collections.

RESULTS: To establish cryopreserved culture strains of two species of Astrephomene, conditions for cryopreservation of the two species were investigated using immature and mature vegetative colonies and two cryoprotectants: N,N-dimethylformamide (DMF) and hydroxyacetone (HA). Rates of cell survival of the A. gubernaculifera or A. perforata strain after two-step cooling and freezing in liquid nitrogen were compared between different concentrations (3 and 6%) of DMF and HA and two types of colonies: immature colonies (small colonies newly released from the parent) and mature colonies (large colonies just before daughter colony formation). The highest rate of survival [11 ± 13% (0.36-33%) by the most probable number (MPN) method] of A. gubernaculifera strain NIES-4017 (established in 2014) was obtained when culture samples of immature colonies were subjected to cryogenic treatment with 6% DMF. In contrast, culture samples of mature colonies subjected to 3% HA cryogenic treatment showed the highest "MPN survival" [5.5 ± 5.9% (0.12-12%)] in A. perforata. Using the optimized cryopreservation conditions for each species, survival after freezing in liquid nitrogen was examined for six other strains of A. gubernaculifera (established from 1962 to 1981) and another A. perforata strain maintained in the Microbial Culture Collection at the National Institute for Environmental Studies (MCC-NIES). We obtained ≥0.1% MPN survival of the A. perforata strain. However, only two of the six strains of A. gubernaculifera showed ≥0.1% MPN survival. By using the optimal cryopreserved conditions obtained for each species, five cryopreserved strains of two species of Astrephomene were established and deposited in the MCC-NIES.

CONCLUSIONS: The optimal cryopreservation conditions differed between the two species of Astrephomene. Cryopreservation of long-term-maintained strains of A. gubernaculifera may be difficult; further studies of cryopreservation of these strains are needed.}, } @article {pmid36646908, year = {2023}, author = {Muñoz-Gómez, SA}, title = {Energetics and evolution of anaerobic microbial eukaryotes.}, journal = {Nature microbiology}, volume = {}, number = {}, pages = {}, pmid = {36646908}, issn = {2058-5276}, abstract = {Mitochondria and aerobic respiration have been suggested to be required for the evolution of eukaryotic cell complexity. Aerobic respiration is several times more energetically efficient than fermentation. Moreover, aerobic respiration occurs at internalized mitochondrial membranes that are not constrained by a sublinear scaling with cell volume. However, diverse and complex anaerobic eukaryotes (for example, free-living and parasitic unicellular, and even small multicellular, eukaryotes) that exclusively rely on fermentation for energy generation have evolved repeatedly from aerobic ancestors. How do fermenting eukaryotes maintain their cell volumes and complexity while relying on such a low energy-yielding process? Here I propose that reduced rates of ATP generation in fermenting versus respiring eukaryotes are compensated for by longer cell cycles that satisfy lifetime energy demands. A literature survey and growth efficiency calculations show that fermenting eukaryotes divide approximately four to six times slower than aerobically respiring counterparts with similar cell volumes. Although ecological advantages such as competition avoidance offset lower growth rates and yields in the short term, fermenting eukaryotes inevitably have fewer physiological and ecological possibilities, which ultimately constrain their long-term evolutionary trajectories.}, } @article {pmid36641836, year = {2023}, author = {Barrenechea Angeles, I and Romero-Martínez, ML and Cavaliere, M and Varrella, S and Francescangeli, F and Piredda, R and Mazzocchi, MG and Montresor, M and Schirone, A and Delbono, I and Margiotta, F and Corinaldesi, C and Chiavarini, S and Montereali, MR and Rimauro, J and Parrella, L and Musco, L and Dell'Anno, A and Tangherlini, M and Pawlowski, J and Frontalini, F}, title = {Encapsulated in sediments: eDNA deciphers the ecosystem history of one of the most polluted European marine sites.}, journal = {Environment international}, volume = {172}, number = {}, pages = {107738}, doi = {10.1016/j.envint.2023.107738}, pmid = {36641836}, issn = {1873-6750}, abstract = {The Anthropocene is characterized by dramatic ecosystem changes driven by human activities. The impact of these activities can be assessed by different geochemical and paleontological proxies. However, each of these proxies provides only a fragmentary insight into the effects of anthropogenic impacts. It is highly challenging to reconstruct, with a holistic view, the state of the ecosystems from the preindustrial period to the present day, covering all biological components, from prokaryotes to multicellular eukaryotes. Here, we used sedimentary ancient DNA (sedaDNA) archives encompassing all trophic levels of biodiversity to reconstruct the two century-natural history in Bagnoli-Coroglio (Gulf of Pozzuoli, Tyrrhenian Sea), one of the most polluted marine-coastal sites in Europe. The site was characterized by seagrass meadows and high eukaryotic diversity until the beginning of the 20th century. Then, the ecosystem completely changed, with seagrasses and associated fauna as well as diverse groups of planktonic and benthic protists being replaced by low diversity biota dominated by dinophyceans and infaunal metazoan species. The sedaDNA analysis revealed a five-phase evolution of the area, where changes appear as the result of a multi-level cascade effect of impacts associated with industrial activities, urbanization, water circulation and land-use changes. The sedaDNA allowed to infer reference conditions that must be considered when restoration actions are to be implemented.}, } @article {pmid36611928, year = {2022}, author = {von der Heyde, B and Hallmann, A}, title = {Cell Type-Specific Pherophorins of Volvox carteri Reveal Interplay of Both Cell Types in ECM Biosynthesis.}, journal = {Cells}, volume = {12}, number = {1}, pages = {}, pmid = {36611928}, issn = {2073-4409}, mesh = {*Volvox/genetics/metabolism ; Phylogeny ; Extracellular Matrix/metabolism ; *Chlorophyta/genetics ; Extracellular Matrix Proteins/metabolism ; }, abstract = {The spheroidal green algae Volvox carteri serves as a model system to investigate the formation of a complex, multifunctional extracellular matrix (ECM) in a relatively simple, multicellular organism with cell differentiation. The V. carteri ECM is mainly composed of hydroxyproline-rich glycoproteins (HRGPs) and there are diverse region-specific, anatomically distinct structures in the ECM. One large protein family with importance for ECM biosynthesis stands out: the pherophorins. The few pherophorins previously extracted from the ECM and characterized, were specifically expressed by somatic cells. However, the localization and function of most pherophorins is unknown. Here, we provide a phylogenetic analysis of 153 pherophorins of V. carteri and its unicellular relative Chlamydomonas reinhardtii. Our analysis of cell type-specific mRNA expression of pherophorins in V. carteri revealed that, contrary to previous assumptions, only about half (52%) of the 102 investigated pherophorin-related genes show stronger expression in somatic cells, whereas about one-third (34%) of the genes show significant higher expression in reproductive cells (gonidia). We fused two pherophorin genes that are expressed by different cell types to yfp, stably expressed them in Volvox and studied the tagged proteins by live-cell imaging. In contrast to earlier biochemical approaches, this genetic approach also allows the in vivo analysis of non-extractable, covalently cross-linked ECM proteins. We demonstrate that the soma-specific pherophorin SSG185 is localized in the outermost ECM structures of the spheroid, the boundary zone and at the flagellar hillocks. SSG185:YFP is detectable as early as 1.5 h after completion of embryogenesis. It is then present for the rest of the life cycle. The gonidia-specific pherophorin PhG is localized in the gonidial cellular zone 1 ("gonidial vesicle") suggesting its involvement in the protection of gonidia and developing embryos until hatching. Even if somatic cells produce the main portion of the ECM of the spheroids, ECM components produced by gonidia are also required to cooperatively assemble the total ECM. Our results provide insights into the evolution of the pherophorin protein family and convey a more detailed picture of Volvox ECM synthesis.}, } @article {pmid36585440, year = {2022}, author = {Lynch, M and Trickovic, B and Kempes, CP}, title = {Evolutionary scaling of maximum growth rate with organism size.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {22586}, pmid = {36585440}, issn = {2045-2322}, support = {R35 GM122566/GM/NIGMS NIH HHS/United States ; }, mesh = {*Biological Evolution ; *Genetic Drift ; Eukaryota/genetics ; Mutation ; Selection, Genetic ; }, abstract = {Data from nearly 1000 species reveal the upper bound to rates of biomass production achievable by natural selection across the Tree of Life. For heterotrophs, maximum growth rates scale positively with organism size in bacteria but negatively in eukaryotes, whereas for phototrophs, the scaling is negligible for cyanobacteria and weakly negative for eukaryotes. These results have significant implications for understanding the bioenergetic consequences of the transition from prokaryotes to eukaryotes, and of the expansion of some groups of the latter into multicellularity. The magnitudes of the scaling coefficients for eukaryotes are significantly lower than expected under any proposed physical-constraint model. Supported by genomic, bioenergetic, and population-genetic data and theory, an alternative hypothesis for the observed negative scaling in eukaryotes postulates that growth-diminishing mutations with small effects passively accumulate with increasing organism size as a consequence of associated increases in the power of random genetic drift. In contrast, conditional on the structural and functional features of ribosomes, natural selection has been able to promote bacteria with the fastest possible growth rates, implying minimal conflicts with both bioenergetic constraints and random genetic drift. If this extension of the drift-barrier hypothesis is correct, the interpretations of comparative studies of biological traits that have traditionally ignored differences in population-genetic environments will require revisiting.}, } @article {pmid36553613, year = {2022}, author = {Kozlov, AP}, title = {The Theory of Carcino-Evo-Devo and Its Non-Trivial Predictions.}, journal = {Genes}, volume = {13}, number = {12}, pages = {}, pmid = {36553613}, issn = {2073-4425}, mesh = {Animals ; Humans ; *Genes, Tumor Suppressor ; Oncogenes ; Cell Differentiation ; *Neoplasms/genetics ; Fishes ; }, abstract = {To explain the sources of additional cell masses in the evolution of multicellular organisms, the theory of carcino-evo-devo, or evolution by tumor neofunctionalization, has been developed. The important demand for a new theory in experimental science is the capability to formulate non-trivial predictions which can be experimentally confirmed. Several non-trivial predictions were formulated using carcino-evo-devo theory, four of which are discussed in the present paper: (1) The number of cellular oncogenes should correspond to the number of cell types in the organism. The evolution of oncogenes, tumor suppressor and differentiation gene classes should proceed concurrently. (2) Evolutionarily new and evolving genes should be specifically expressed in tumors (TSEEN genes). (3) Human orthologs of fish TSEEN genes should acquire progressive functions connected with new cell types, tissues and organs. (4) Selection of tumors for new functions in the organism is possible. Evolutionarily novel organs should recapitulate tumor features in their development. As shown in this paper, these predictions have been confirmed by the laboratory of the author. Thus, we have shown that carcino-evo-devo theory has predictive power, fulfilling a fundamental requirement for a new theory.}, } @article {pmid36550365, year = {2022}, author = {Bowman, JL}, title = {The origin of a land flora.}, journal = {Nature plants}, volume = {8}, number = {12}, pages = {1352-1369}, pmid = {36550365}, issn = {2055-0278}, mesh = {*Biological Evolution ; Phylogeny ; Plants/genetics ; *Embryophyta/genetics ; }, abstract = {The origin of a land flora fundamentally shifted the course of evolution of life on earth, facilitating terrestrialization of other eukaryotic lineages and altering the planet's geology, from changing atmospheric and hydrological cycles to transforming continental erosion processes. Despite algal lineages inhabiting the terrestrial environment for a considerable preceding period, they failed to evolve complex multicellularity necessary to conquer the land. About 470 million years ago, one lineage of charophycean alga evolved complex multicellularity via developmental innovations in both haploid and diploid generations and became land plants (embryophytes), which rapidly diversified to dominate most terrestrial habitats. Genome sequences have provided unprecedented insights into the genetic and genomic bases for embryophyte origins, with some embryophyte-specific genes being associated with the evolution of key developmental or physiological attributes, such as meristems, rhizoids and the ability to form mycorrhizal associations. However, based on the fossil record, the evolution of the defining feature of embryophytes, the embryo, and consequently the sporangium that provided a reproductive advantage, may have been most critical in their rise to dominance. The long timeframe and singularity of a land flora were perhaps due to the stepwise assembly of a large constellation of genetic innovations required to conquer the terrestrial environment.}, } @article {pmid36547392, year = {2022}, author = {Baselga-Cervera, B and Gettle, N and Travisano, M}, title = {Loss-of-heterozygosity facilitates a fitness valley crossing in experimentally evolved multicellular yeast.}, journal = {Proceedings. Biological sciences}, volume = {289}, number = {1976}, pages = {20212722}, pmid = {36547392}, issn = {1471-2954}, mesh = {*Adaptation, Physiological/genetics ; *Biological Evolution ; Genotype ; Heterozygote ; *Saccharomyces cerevisiae/genetics ; *Loss of Heterozygosity ; *Genetic Fitness ; }, abstract = {Determining how adaptive possibilities do or do not become evolutionary realities is central to understanding the tempo and mode of evolutionary change. Some of the simplest evolutionary landscapes arise from underdominance at a single locus where the fitness valley consists of only one less-fit genotype. Despite their potential for rapid evolutionary change, few such examples have been investigated. We capitalized on an experimental system in which a significant evolutionary shift, the transition from uni-to-multicellularity, was observed in asexual diploid populations of Saccharomyces cerevisiae experimentally selected for increased settling rates. The multicellular phenotype results from recessive single-locus mutations that undergo loss-of-heterozygosity (LOH) events. By reconstructing the necessary heterozygous intermediate steps, we found that the evolution of multicellularity involves a decrease in size during the first steps. Heterozygous genotypes are 20% smaller in size than genotypes with functional alleles. Nevertheless, populations of heterozygotes give rise to multicellular genotypes more readily than unicellular genotypes with two functional alleles, by rapid LOH events. LOH drives adaptation that may enable rapid evolution in diploid yeast. Together these results show discordance between the phenotypic and genotypic multicellular transition. The evolutionary path to multicellularity, and the adaptive benefits of increased size, requires initial size reductions.}, } @article {pmid36531949, year = {2022}, author = {Nguyen, NM and Merle, T and Broders-Bondon, F and Brunet, AC and Battistella, A and Land, EBL and Sarron, F and Jha, A and Gennisson, JL and Röttinger, E and Fernández-Sánchez, ME and Farge, E}, title = {Mechano-biochemical marine stimulation of inversion, gastrulation, and endomesoderm specification in multicellular Eukaryota.}, journal = {Frontiers in cell and developmental biology}, volume = {10}, number = {}, pages = {992371}, pmid = {36531949}, issn = {2296-634X}, abstract = {The evolutionary emergence of the primitive gut in Metazoa is one of the decisive events that conditioned the major evolutionary transition, leading to the origin of animal development. It is thought to have been induced by the specification of the endomesoderm (EM) into the multicellular tissue and its invagination (i.e., gastrulation). However, the biochemical signals underlying the evolutionary emergence of EM specification and gastrulation remain unknown. Herein, we find that hydrodynamic mechanical strains, reminiscent of soft marine flow, trigger active tissue invagination/gastrulation or curvature reversal via a Myo-II-dependent mechanotransductive process in both the metazoan Nematostella vectensis (cnidaria) and the multicellular choanoflagellate Choanoeca flexa. In the latter, our data suggest that the curvature reversal is associated with a sensory-behavioral feeding response. Additionally, like in bilaterian animals, gastrulation in the cnidarian Nematostella vectensis is shown to participate in the biochemical specification of the EM through mechanical activation of the β-catenin pathway via the phosphorylation of Y654-βcatenin. Choanoflagellates are considered the closest living relative to metazoans, and the common ancestor of choanoflagellates and metazoans dates back at least 700 million years. Therefore, the present findings using these evolutionarily distant species suggest that the primitive emergence of the gut in Metazoa may have been initiated in response to marine mechanical stress already in multicellular pre-Metazoa. Then, the evolutionary transition may have been achieved by specifying the EM via a mechanosensitive Y654-βcatenin dependent mechanism, which appeared during early Metazoa evolution and is specifically conserved in all animals.}, } @article {pmid36526191, year = {2023}, author = {Barbosa, FAS and Brait, LAS and Coutinho, FH and Ferreira, CM and Moreira, EF and de Queiroz Salles, L and Meirelles, PM}, title = {Ecological landscape explains aquifers microbial structure.}, journal = {The Science of the total environment}, volume = {862}, number = {}, pages = {160822}, doi = {10.1016/j.scitotenv.2022.160822}, pmid = {36526191}, issn = {1879-1026}, mesh = {Humans ; *Groundwater/chemistry ; Bacteria/metabolism ; Water Quality ; Gram-Negative Bacteria ; *Microbiota ; }, abstract = {Aquifers have significant social, economic, and ecological importance. They supply 30 % of the freshwater for human consumption worldwide, including agricultural and industrial use. Despite aquifers' importance, the relationships between aquifer categories and their inhabiting microbial communities are still unknown. Characterizing variations within microbial communities' function and taxonomy structure at different aquifers could give a panoramic view of patterns that may enable the detection and prediction of environmental impact caused by multiple sources. Using publicly available shotgun metagenomic datasets, we examined whether soil properties, land use, and climate variables would have a more significant influence on the taxonomy and functional structure of the microbial communities than the ecological landscapes of the aquifer (i.e., Karst, Porous, Saline, Geyser, and Porous Contaminated). We found that these categories are stronger predictors of microbial communities' structure than geographical localization. In addition, our results show that microbial richness and dominance patterns are the opposite of those found in multicellular life, where extreme habitats harbour richer functional and taxonomic microbial communities. We found that low-abundant and recently described candidate taxa, such as the chemolithoautotrophic genus Candidatus Altiarcheum and the Candidate phylum Parcubacteria, are the main contributors to aquifer microbial communities' dissimilarities. Genes related to gram-negative bacteria proteins, cell wall structures, and phage activity were the primary contributors to aquifer microbial communities' dissimilarities among the aquifers' ecological landscapes. The results reported in the present study highlight the utility of using ecological landscapes for investigating aquifer microbial communities. In addition, we suggest that functions played by recently described and low abundant bacterial groups need further investigation once they might affect water quality, geochemical cycles, and the effects of anthropogenic disturbances such as pollution and climatic events on aquifers.}, } @article {pmid36499258, year = {2022}, author = {Vainshelbaum, NM and Giuliani, A and Salmina, K and Pjanova, D and Erenpreisa, J}, title = {The Transcriptome and Proteome Networks of Malignant Tumours Reveal Atavistic Attractors of Polyploidy-Related Asexual Reproduction.}, journal = {International journal of molecular sciences}, volume = {23}, number = {23}, pages = {}, pmid = {36499258}, issn = {1422-0067}, mesh = {Animals ; Humans ; *Gene Duplication ; Genome, Plant ; Proteome/genetics ; Evolution, Molecular ; Polyploidy ; Transcriptome ; *Neoplasms/genetics ; Mammals/genetics ; }, abstract = {The expression of gametogenesis-related (GG) genes and proteins, as well as whole genome duplications (WGD), are the hallmarks of cancer related to poor prognosis. Currently, it is not clear if these hallmarks are random processes associated only with genome instability or are programmatically linked. Our goal was to elucidate this via a thorough bioinformatics analysis of 1474 GG genes in the context of WGD. We examined their association in protein-protein interaction and coexpression networks, and their phylostratigraphic profiles from publicly available patient tumour data. The results show that GG genes are upregulated in most WGD-enriched somatic cancers at the transcriptome level and reveal robust GG gene expression at the protein level, as well as the ability to associate into correlation networks and enrich the reproductive modules. GG gene phylostratigraphy displayed in WGD+ cancers an attractor of early eukaryotic origin for DNA recombination and meiosis, and one relative to oocyte maturation and embryogenesis from early multicellular organisms. The upregulation of cancer-testis genes emerging with mammalian placentation was also associated with WGD. In general, the results suggest the role of polyploidy for soma-germ transition accessing latent cancer attractors in the human genome network, which appear as pre-formed along the whole Evolution of Life.}, } @article {pmid36497057, year = {2022}, author = {Aktas, RG and Karski, M and Issac, B and Sun, L and Rockowitz, S and Sliz, P and Vakili, K}, title = {Long-Term Characteristics of Human-Derived Biliary Organoids under a Single Continuous Culture Condition.}, journal = {Cells}, volume = {11}, number = {23}, pages = {}, pmid = {36497057}, issn = {2073-4409}, mesh = {Humans ; Child ; *Organoids ; *Epithelial Cells ; }, abstract = {Organoids have been used to investigate the three-dimensional (3D) organization and function of their respective organs. These self-organizing 3D structures offer a distinct advantage over traditional two-dimensional (2D) culture techniques by creating a more physiologically relevant milieu to study complex biological systems. The goal of this study was to determine the feasibility of establishing organoids from various pediatric liver diseases and characterize the long-term evolution of cholangiocyte organoids (chol-orgs) under a single continuous culture condition. We established chol-orgs from 10 different liver conditions and characterized their multicellular organization into complex epithelial structures through budding, merging, and lumen formation. Immunofluorescent staining, electron microscopy, and single-nucleus RNA (snRNA-seq) sequencing confirmed the cholangiocytic nature of the chol-orgs. There were significant cell population differences in the transcript profiles of two-dimensional and organoid cultures based on snRNA-seq. Our study provides an approach for the generation and long-term maintenance of chol-orgs from various pediatric liver diseases under a single continuous culture condition.}, } @article {pmid36494694, year = {2022}, author = {Sun, H and Fang, T and Wang, T and Yu, Z and Gong, L and Wei, X and Wang, H and He, Y and Liu, L and Yan, Y and Sui, W and Xu, Y and Yi, S and Qiu, L and Hao, M}, title = {Single-cell profiles reveal tumor cell heterogeneity and immunosuppressive microenvironment in Waldenström macroglobulinemia.}, journal = {Journal of translational medicine}, volume = {20}, number = {1}, pages = {576}, pmid = {36494694}, issn = {1479-5876}, mesh = {Humans ; *Ecosystem ; *Waldenstrom Macroglobulinemia/genetics/pathology ; Bone Marrow/pathology ; Tumor Microenvironment ; B-Lymphocytes/pathology ; }, abstract = {BACKGROUND: Waldenström macroglobulinemia (WM) is a rare and incurable indolent B-cell malignancy. The molecular pathogenesis and the role of immunosuppressive microenvironment in WM development are still incompletely understood.

METHODS: The multicellular ecosystem in bone marrow (BM) of WM were delineated by single-cell RNA-sequencing (scRNA-seq) and investigated the underlying molecular characteristics.

RESULTS: Our data uncovered the heterogeneity of malignant cells in WM, and investigated the kinetic co-evolution of WM and immune cells, which played pivotal roles in disease development and progression. Two novel subpopulations of malignant cells, CD19[+]CD3[+] and CD138[+]CD3[+], co-expressing T-cell marker genes were identified at single-cell resolution. Pseudotime-ordered analysis elucidated that CD19[+]CD3[+] malignant cells presented at an early stage of WM-B cell differentiation. Colony formation assay further identified that CD19[+]CD3[+] malignant cells acted as potential WM precursors. Based on the findings of T cell marker aberrant expressed on WM tumor cells, we speculate the long-time activation of tumor antigen-induced immunosuppressive microenvironment that is involved in the pathogenesis of WM. Therefore, our study further investigated the possible molecular mechanism of immune cell dysfunction. A precursor exhausted CD8-T cells and functional deletion of NK cells were identified in WM, and CD47 would be a potential therapeutic target to reverse the dysfunction of immune cells.

CONCLUSIONS: Our study facilitates further understanding of the biological heterogeneity of tumor cells and immunosuppressive microenvironment in WM. These data may have implications for the development of novel immunotherapies, such as targeting pre-exhausted CD8-T cells in WM.}, } @article {pmid36476840, year = {2022}, author = {Nakabachi, A and Inoue, H and Hirose, Y}, title = {High-resolution Microbiome Analyses of Nine Psyllid Species of the Family Triozidae Identified Previously Unrecognized but Major Bacterial Populations, including Liberibacter and Wolbachia of Supergroup O.}, journal = {Microbes and environments}, volume = {37}, number = {4}, pages = {}, pmid = {36476840}, issn = {1347-4405}, mesh = {Humans ; Animals ; Liberibacter ; *Wolbachia/genetics ; *Hemiptera ; RNA, Ribosomal, 16S/genetics ; Europe ; }, abstract = {Psyllids (Hemiptera: Sternorrhyncha: Psylloidea) are plant sap-sucking insects that include important agricultural pests. To obtain insights into the ecological and evolutionary behaviors of microbes, including plant pathogens, in Psylloidea, high-resolution ana-lyses of the microbiomes of nine psyllid species belonging to the family Triozidae were performed using high-throughput amplicon sequencing of the 16S rRNA gene. Analyses identified various bacterial populations, showing that all nine psyllids have at least one secondary symbiont, along with the primary symbiont "Candidatus Carsonella ruddii" (Gammaproteobacteria: Oceanospirillales: Halomonadaceae). The majority of the secondary symbionts were gammaproteobacteria, particularly those of the order Enterobacterales, which included Arsenophonus and Serratia symbiotica, a bacterium formerly recognized only as a secondary symbiont of aphids (Hemiptera: Sternorrhyncha: Aphidoidea). The non-Enterobacterales gammaproteobacteria identified in the present study were Diplorickettsia (Diplorickettsiales: Diplorickettsiaceae), a potential human pathogen, and Carnimonas (Oceanospirillales: Halomonadaceae), a lineage detected for the first time in Psylloidea. Regarding alphaproteobacteria, the potential plant pathogen "Ca. Liberibacter europaeus" (Rhizobiales: Rhizobiaceae) was detected for the first time in Epitrioza yasumatsui, which feeds on the Japanese silverberry Elaeagnus umbellata (Elaeagnaceae), an aggressive invasive plant in the United States and Europe. Besides the detection of Wolbachia (Rickettsiales: Anaplasmataceae) of supergroup B in three psyllid species, a lineage belonging to supergroup O was identified for the first time in Psylloidea. These results suggest the rampant transfer of bacterial symbionts among animals and plants, thereby providing deeper insights into the evolution of interkingdom interactions among multicellular organisms and bacteria, which will facilitate the control of pest psyllids.}, } @article {pmid36460873, year = {2022}, author = {Niculescu, VF}, title = {A comment on the article Jaques et al. "Origin and evolution of animal multicellularity in light of phylogenomics and cancer genetics ".}, journal = {Medical oncology (Northwood, London, England)}, volume = {40}, number = {1}, pages = {38}, pmid = {36460873}, issn = {1559-131X}, mesh = {Animals ; Humans ; Phylogeny ; *Health Personnel ; *Neoplasms/genetics ; }, abstract = {For developmental biologists, the work of Jaques et al. is quite surprising. It suggests that cancer genetics and cancer phylogenomics may contribute to the origin and evolution of multicellularity in animals. My commentary complements the work of Jaques et al. from the perspective of evolutionary life cycle biology and recalls the statement of Douglas H. Erwin, who said that understanding life cycle evolution is (equally) crucial to subsequent steps [1].}, } @article {pmid36447160, year = {2022}, author = {Liu, Y and Ma, Y and Aray, H and Lan, H}, title = {Morphogenesis and cell wall composition of trichomes and their function in response to salt in halophyte Salsola ferganica.}, journal = {BMC plant biology}, volume = {22}, number = {1}, pages = {551}, pmid = {36447160}, issn = {1471-2229}, mesh = {*Salsola ; Salt-Tolerant Plants/genetics ; Trichomes ; *Arabidopsis/genetics ; Sodium Chloride ; Cell Wall ; Morphogenesis ; Gossypium ; }, abstract = {BACKGROUND: To survive harsh environmental conditions, desert plants show various adaptions, such as the evolution of trichomes, which are protective epidermal protrusions. Currently, the morphogenesis and function of trichomes in desert plants are not well understood. Salsola ferganica is an annual halophyte distributed in cold deserts; at the seedling stage, its rod-shaped true leaves are covered with long and thick trichomes and are affected by habitat conditions. Therefore, we evaluated the trichomes on morphogenesis and cell wall composition of S. ferganica compared to Arabidopsis thaliana and cotton, related gene expression, and preliminary function in salt accumulation of the leaves.

RESULTS: The trichomes of S. ferganica were initiated from the epidermal primordium, followed by two to three rounds of cell division to form a multicellular trichome, while some genes associated with them were positively involved. Cell wall composition analysis showed that different polysaccharides including heavily methyl-esterified and fully de-esterified pectins (before maturation, probably in the primary wall), xyloglucans (in the mid-early and middle stages, probably in the secondary wall), and extensin (during the whole developmental period) were detected, which were different from those found in trichomes of Arabidopsis and cotton. Moreover, trichome development was affected by abiotic stress, and might accumulate salt from the mesophyll cells and secrete outside.

CONCLUSIONS: S. ferganica has multicellular, non-branched trichomes that undergo two to three rounds of cell division and are affected by abiotic stress. They have a unique cell wall composition which is different from that of Arabidopsis and cotton. Furthermore, several genes positively or negatively regulate trichome development. Our findings should contribute to our further understanding of the biogenesis and adaptation of plant accessory structures in desert plant species.}, } @article {pmid36434792, year = {2022}, author = {Zhan, A and Luo, Y and Qin, H and Lin, W and Tian, L}, title = {Hypomagnetic Field Exposure Affecting Gut Microbiota, Reactive Oxygen Species Levels, and Colonic Cell Proliferation in Mice.}, journal = {Bioelectromagnetics}, volume = {43}, number = {8}, pages = {462-475}, doi = {10.1002/bem.22427}, pmid = {36434792}, issn = {1521-186X}, mesh = {Animals ; Mice ; Cell Proliferation ; *Colon ; *Gastrointestinal Microbiome ; Mice, Inbred C57BL ; *Reactive Oxygen Species ; }, abstract = {The gut microbiota has been considered one of the key factors in host health, which is influenced by many environmental factors. The geomagnetic field (GMF) represents one of the important environmental conditions for living organisms. Previous studies have shown that the elimination of GMF, the so-called hypomagnetic field (HMF), could affect the physiological functions and resistance to antibiotics of some microorganisms. However, whether long-term HMF exposure could alter the gut microbiota to some extent in mammals remains unclear. Here, we investigated the effects of long-term (8- and 12-week) HMF exposure on the gut microbiota in C57BL/6J mice. Our results clearly showed that 8-week HMF significantly affected the diversity and function of the mouse gut microbiota. Compared with the GMF group, the concentrations of short-chain fatty acids tended to decrease in the HMF group. Immunofluorescence analysis showed that HMF promoted colonic cell proliferation, concomitant with an increased level of reactive oxygen species (ROS). To our knowledge, this is the first in vivo finding that long-term HMF exposure could affect the mouse gut microbiota, ROS levels, and colonic cell proliferation in the colon. Moreover, the changes in gut microbiota can be restored by returning mice to the GMF environment, thus the possible harm to the microbiota caused by HMF exposure can be alleviated. © 2022 Bioelectromagnetics Society.}, } @article {pmid36433975, year = {2022}, author = {Kreider, JJ and Janzen, T and Bernadou, A and Elsner, D and Kramer, BH and Weissing, FJ}, title = {Resource sharing is sufficient for the emergence of division of labour.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {7232}, pmid = {36433975}, issn = {2041-1723}, mesh = {Animals ; Female ; Pregnancy ; *Biological Evolution ; *Labor, Obstetric ; }, abstract = {Division of labour occurs in a broad range of organisms. Yet, how division of labour can emerge in the absence of pre-existing interindividual differences is poorly understood. Using a simple but realistic model, we show that in a group of initially identical individuals, division of labour emerges spontaneously if returning foragers share part of their resources with other group members. In the absence of resource sharing, individuals follow an activity schedule of alternating between foraging and other tasks. If non-foraging individuals are fed by other individuals, their alternating activity schedule becomes interrupted, leading to task specialisation and the emergence of division of labour. Furthermore, nutritional differences between individuals reinforce division of labour. Such differences can be caused by increased metabolic rates during foraging or by dominance interactions during resource sharing. Our model proposes a plausible mechanism for the self-organised emergence of division of labour in animal groups of initially identical individuals. This mechanism could also play a role for the emergence of division of labour during the major evolutionary transitions to eusociality and multicellularity.}, } @article {pmid36430514, year = {2022}, author = {Ojosnegros, S and Alvarez, JM and Grossmann, J and Gagliardini, V and Quintanilla, LG and Grossniklaus, U and Fernández, H}, title = {The Shared Proteome of the Apomictic Fern Dryopteris affinis ssp. affinis and Its Sexual Relative Dryopteris oreades.}, journal = {International journal of molecular sciences}, volume = {23}, number = {22}, pages = {}, pmid = {36430514}, issn = {1422-0067}, mesh = {*Dryopteris/genetics ; *Ferns/genetics ; Proteome ; Proteomics ; Plant Growth Regulators ; }, abstract = {Ferns are a diverse evolutionary lineage, sister to the seed plants, which is of great ecological importance and has a high biotechnological potential. Fern gametophytes represent one of the simplest autotrophic, multicellular plant forms and show several experimental advantages, including a simple and space-efficient in vitro culture system. However, the molecular basis of fern growth and development has hardly been studied. Here, we report on a proteomic study that identified 417 proteins shared by gametophytes of the apogamous fern Dryopteris affinis ssp. affinis and its sexual relative Dryopteris oreades. Most proteins are predicted to localize to the cytoplasm, the chloroplast, or the nucleus, and are linked to enzymatic, binding, and structural activities. A subset of 145 proteins are involved in growth, reproduction, phytohormone signaling and biosynthesis, and gene expression, including homologs of SHEPHERD (SHD), HEAT SHOCK PROTEIN 90-5 (CR88), TRP4, BOBBER 1 (BOB1), FLAVONE 3'-O-METHYLTRANSFERASE 1 (OMT1), ZEAXANTHIN EPOXIDASE (ABA1), GLUTAMATE DESCARBOXYLASE 1 (GAD), and dsRNA-BINDING DOMAIN-LIKE SUPERFAMILY PROTEIN (HLY1). Nearly 25% of the annotated proteins are associated with responses to biotic and abiotic stimuli. As for biotic stress, the proteins PROTEIN SGT1 HOMOLOG B (SGT1B), SUPPRESSOR OF SA INSENSITIVE2 (SSI2), PHOSPHOLIPASE D ALPHA 1 (PLDALPHA1), SERINE/THREONINE-PROTEIN KINASE SRK2E (OST1), ACYL CARRIER PROTEIN 4 (ACP4), and NONHOST RESISTANCE TO P. S. PHASEOLICOLA1 (GLPK) are worth mentioning. Regarding abiotic stimuli, we found proteins associated with oxidative stress: SUPEROXIDE DISMUTASE[CU-ZN] 1 (CSD1), and GLUTATHIONE S-TRANSFERASE U19 (GSTU19), light intensity SERINE HYDROXYMETHYLTRANSFERASE 1 (SHM1) and UBIQUITIN-CONJUGATING ENZYME E2 35 (UBC35), salt and heavy metal stress included MITOCHONDRIAL PHOSPHATE CARRIER PROTEIN 3 (PHT3;1), as well as drought and thermotolerance: LEA7, DEAD-BOX ATP-DEPENDENT RNA HELICASE 38 (LOS4), and abundant heat-shock proteins and other chaperones. In addition, we identified interactomes using the STRING platform, revealing protein-protein associations obtained from co-expression, co-occurrence, text mining, homology, databases, and experimental datasets. By focusing on ferns, this proteomic study increases our knowledge on plant development and evolution, and may inspire future applications in crop species.}, } @article {pmid36421702, year = {2022}, author = {Sowa, ST and Bosetti, C and Galera-Prat, A and Johnson, MS and Lehtiö, L}, title = {An Evolutionary Perspective on the Origin, Conservation and Binding Partner Acquisition of Tankyrases.}, journal = {Biomolecules}, volume = {12}, number = {11}, pages = {}, pmid = {36421702}, issn = {2218-273X}, mesh = {Humans ; Animals ; *Tankyrases/genetics/chemistry/metabolism ; Telomere Homeostasis ; Wnt Signaling Pathway ; }, abstract = {Tankyrases are poly-ADP-ribosyltransferases that regulate many crucial and diverse cellular processes in humans such as Wnt signaling, telomere homeostasis, mitotic spindle formation and glucose metabolism. While tankyrases are present in most animals, functional differences across species may exist. In this work, we confirm the widespread distribution of tankyrases throughout the branches of multicellular animal life and identify the single-celled choanoflagellates as earliest origin of tankyrases. We further show that the sequences and structural aspects of TNKSs are well-conserved even between distantly related species. We also experimentally characterized an anciently diverged tankyrase homolog from the sponge Amphimedon queenslandica and show that the basic functional aspects, such as poly-ADP-ribosylation activity and interaction with the canonical tankyrase binding peptide motif, are conserved. Conversely, the presence of tankyrase binding motifs in orthologs of confirmed interaction partners varies greatly between species, indicating that tankyrases may have different sets of interaction partners depending on the animal lineage. Overall, our analysis suggests a remarkable degree of conservation for tankyrases, and that their regulatory functions in cells have likely changed considerably throughout evolution.}, } @article {pmid36404107, year = {2023}, author = {Sepp, T and Giraudeau, M}, title = {Wild animals as an underused treasure trove for studying the genetics of cancer.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {45}, number = {2}, pages = {e2200188}, doi = {10.1002/bies.202200188}, pmid = {36404107}, issn = {1521-1878}, mesh = {Animals ; Humans ; *Animals, Wild/genetics ; Ecology ; Biodiversity ; *Neoplasms/genetics ; Genomics ; }, abstract = {Recent years have seen an emergence of the field of comparative cancer genomics. However, the advancements in this field are held back by the hesitation to use knowledge obtained from human studies to study cancer in other animals, and vice versa. Since cancer is an ancient disease that arose with multicellularity, oncogenes and tumour-suppressor genes are amongst the oldest gene classes, shared by most animal species. Acknowledging that other animals are, in terms of cancer genetics, ecology, and evolution, rather similar to humans, creates huge potential for advancing the fields of human and animal oncology, but also biodiversity conservation. Also see the video abstract here: https://youtu.be/UFqyMx5HETY.}, } @article {pmid36384644, year = {2022}, author = {Pinskey, JM and Lagisetty, A and Gui, L and Phan, N and Reetz, E and Tavakoli, A and Fu, G and Nicastro, D}, title = {Three-dimensional flagella structures from animals' closest unicellular relatives, the Choanoflagellates.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {36384644}, issn = {2050-084X}, support = {F32 GM137470/GM/NIGMS NIH HHS/United States ; R01 GM083122/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Choanoflagellata/metabolism ; Cryoelectron Microscopy ; Flagella ; Axoneme ; Cilia ; }, abstract = {In most eukaryotic organisms, cilia and flagella perform a variety of life-sustaining roles related to environmental sensing and motility. Cryo-electron microscopy has provided considerable insight into the morphology and function of flagellar structures, but studies have been limited to less than a dozen of the millions of known eukaryotic species. Ultrastructural information is particularly lacking for unicellular organisms in the Opisthokonta clade, leaving a sizeable gap in our understanding of flagella evolution between unicellular species and multicellular metazoans (animals). Choanoflagellates are important aquatic heterotrophs, uniquely positioned within the opisthokonts as the metazoans' closest living unicellular relatives. We performed cryo-focused ion beam milling and cryo-electron tomography on flagella from the choanoflagellate species Salpingoeca rosetta. We show that the axonemal dyneins, radial spokes, and central pair complex in S. rosetta more closely resemble metazoan structures than those of unicellular organisms from other suprakingdoms. In addition, we describe unique features of S. rosetta flagella, including microtubule holes, microtubule inner proteins, and the flagellar vane: a fine, net-like extension that has been notoriously difficult to visualize using other methods. Furthermore, we report barb-like structures of unknown function on the extracellular surface of the flagellar membrane. Together, our findings provide new insights into choanoflagellate biology and flagella evolution between unicellular and multicellular opisthokonts.}, } @article {pmid36379956, year = {2022}, author = {Huang, J and Zhao, L and Malik, S and Gentile, BR and Xiong, V and Arazi, T and Owen, HA and Friml, J and Zhao, D}, title = {Specification of female germline by microRNA orchestrated auxin signaling in Arabidopsis.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {6960}, pmid = {36379956}, issn = {2041-1723}, mesh = {*Arabidopsis/metabolism ; *Arabidopsis Proteins/metabolism ; *MicroRNAs/genetics/metabolism ; Gene Expression Regulation, Plant ; Indoleacetic Acids/metabolism ; Germ Cells/metabolism ; Transcription Factors/metabolism ; }, abstract = {Germline determination is essential for species survival and evolution in multicellular organisms. In most flowering plants, formation of the female germline is initiated with specification of one megaspore mother cell (MMC) in each ovule; however, the molecular mechanism underlying this key event remains unclear. Here we report that spatially restricted auxin signaling promotes MMC fate in Arabidopsis. Our results show that the microRNA160 (miR160) targeted gene ARF17 (AUXIN RESPONSE FACTOR17) is required for promoting MMC specification by genetically interacting with the SPL/NZZ (SPOROCYTELESS/NOZZLE) gene. Alterations of auxin signaling cause formation of supernumerary MMCs in an ARF17- and SPL/NZZ-dependent manner. Furthermore, miR160 and ARF17 are indispensable for attaining a normal auxin maximum at the ovule apex via modulating the expression domain of PIN1 (PIN-FORMED1) auxin transporter. Our findings elucidate the mechanism by which auxin signaling promotes the acquisition of female germline cell fate in plants.}, } @article {pmid36372985, year = {2022}, author = {Durbagula, S and Korlimarla, A and Ravikumar, G and Valiya Parambath, S and Kaku, SM and Visweswariah, AM}, title = {Prenatal epigenetic factors are predisposing for neurodevelopmental disorders-Considering placenta as a model.}, journal = {Birth defects research}, volume = {114}, number = {20}, pages = {1324-1342}, doi = {10.1002/bdr2.2119}, pmid = {36372985}, issn = {2472-1727}, mesh = {Animals ; Pregnancy ; Female ; *Placenta/metabolism ; *Neurodevelopmental Disorders/genetics ; Epigenomics ; Epigenesis, Genetic ; Fetal Development/physiology ; }, abstract = {The heterogeneous characteristics of neurodevelopmental disorders (NDDs) have resulted in varied perspectives on their causation. The biology behind the phenotypic heterogeneity in NDDs is not yet well-defined, but a strong genetic basis has become well accepted as causal for NDDs. Alongside this, there is growing focus on epigenetic mechanisms. The evidence mounting for in-utero origins of NDDs has promoted research focused on epigenetic mechanisms that impact genes that program early brain development. Considering that placenta is a vital organ, this review emphasizes the prenatal factors and their effects on epigenetic changes influencing the normal functioning of the placenta, and factors mediating pathology in the developing fetus. Overall, it is an attempt to bring focus on the hypothesis that "Prenatal epigenetic factors in the placenta could be predisposing to NDDs (with special interest on autism spectrum disorders)." This review finds growing evidence for epigenetic modifications in the placenta that affect glucocorticoid, nutrient, and immune signaling pathways, eventually impacting fetal brain development. This evidence largely comes from animal models. Given the multicellular nature of placenta, we conclude that, there is a need for placental research focused on employing single-cell approaches and genome-wide methylation profiles to bring insights into specific molecular pathways in the placenta that regulate early brain development.}, } @article {pmid36356576, year = {2022}, author = {Peterson, AF and Ingram, K and Huang, EJ and Parksong, J and McKenney, C and Bever, GS and Regot, S}, title = {Systematic analysis of the MAPK signaling network reveals MAP3K-driven control of cell fate.}, journal = {Cell systems}, volume = {13}, number = {11}, pages = {885-894.e4}, doi = {10.1016/j.cels.2022.10.003}, pmid = {36356576}, issn = {2405-4720}, mesh = {Humans ; *JNK Mitogen-Activated Protein Kinases/metabolism ; *MAP Kinase Signaling System ; Phosphorylation ; Mitogen-Activated Protein Kinases/metabolism ; Signal Transduction ; }, abstract = {The classic network of mitogen-activated protein kinases (MAPKs) is highly interconnected and controls a diverse array of biological processes. In multicellular eukaryotes, the MAPKs ERK, JNK, and p38 control opposing cell behaviors but are often activated simultaneously, raising questions about how input-output specificity is achieved. Here, we use multiplexed MAPK activity biosensors to investigate how cell fate control emerges from the connectivity and dynamics of the MAPK network. Through chemical and genetic perturbation, we systematically explore the outputs and functions of all the MAP3 kinases encoded in the human genome and show that MAP3Ks control cell fate by triggering unique combinations of MAPK activity. We show that these MAPK activity combinations explain the paradoxical dual role of JNK signaling as pro-apoptotic or pro-proliferative kinase. Overall, our integrative analysis indicates that the MAPK network operates as a unit to control cell fate and shifts the focus from MAPKs to MAP3Ks to better understand signaling-mediated control of cell fate.}, } @article {pmid36342925, year = {2022}, author = {Oda, AH and Tamura, M and Kaneko, K and Ohta, K and Hatakeyama, TS}, title = {Autotoxin-mediated latecomer killing in yeast communities.}, journal = {PLoS biology}, volume = {20}, number = {11}, pages = {e3001844}, pmid = {36342925}, issn = {1545-7885}, mesh = {Humans ; *Saccharomyces cerevisiae/genetics ; *Yeast, Dried ; Cell Death ; Germ Cells ; Glucose ; }, abstract = {Cellular adaptation to stressful environments such as starvation is essential to the survival of microbial communities, but the uniform response of the cell community may lead to entire cell death or severe damage to their fitness. Here, we demonstrate an elaborate response of the yeast community against glucose depletion, in which the first adapted cells kill the latecomer cells. During glucose depletion, yeast cells release autotoxins, such as leucic acid and L-2keto-3methylvalerate, which can even kill the clonal cells of the ones producing them. Although these autotoxins were likely to induce mass suicide, some cells differentiated to adapt to the autotoxins without genetic changes. If nondifferentiated latecomers tried to invade the habitat, autotoxins damaged or killed the latecomers, but the differentiated cells could selectively survive. Phylogenetically distant fission and budding yeast shared this behavior using the same autotoxins, suggesting that latecomer killing may be the universal system of intercellular communication, which may be relevant to the evolutional transition from unicellular to multicellular organisms.}, } @article {pmid36331628, year = {2022}, author = {Alvarez, FE and Carrillo, JA and Clairambault, J}, title = {Evolution of a structured cell population endowed with plasticity of traits under constraints on and between the traits.}, journal = {Journal of mathematical biology}, volume = {85}, number = {6-7}, pages = {64}, pmid = {36331628}, issn = {1432-1416}, mesh = {Animals ; Phenotype ; Population Dynamics ; *Biological Evolution ; }, abstract = {Confronted with the biological problem of managing plasticity in cell populations, which is in particular responsible for transient and reversible drug resistance in cancer, we propose a rationale consisting of an integro-differential and a reaction-advection-diffusion equation, the properties of which are studied theoretically and numerically. By using a constructive finite volume method, we show the existence and uniqueness of a weak solution and illustrate by numerical approximations and their simulations the capacity of the model to exhibit divergence of traits. This feature may be theoretically interpreted as describing a physiological step towards multicellularity in animal evolution and, closer to present-day clinical challenges in oncology, as a possible representation of bet hedging in cancer cell populations.}, } @article {pmid36329610, year = {2022}, author = {Banijamali, M and Höjer, P and Nagy, A and Hååg, P and Gomero, EP and Stiller, C and Kaminskyy, VO and Ekman, S and Lewensohn, R and Karlström, AE and Viktorsson, K and Ahmadian, A}, title = {Characterizing single extracellular vesicles by droplet barcode sequencing for protein analysis.}, journal = {Journal of extracellular vesicles}, volume = {11}, number = {11}, pages = {e12277}, pmid = {36329610}, issn = {2001-3078}, mesh = {Humans ; *Extracellular Vesicles/genetics ; Biomarkers/metabolism ; Cell Line ; Membrane Proteins/metabolism ; }, abstract = {Small extracellular vesicles (sEVs) have in recent years evolved as a source of biomarkers for disease diagnosis and therapeutic follow up. sEV samples derived from multicellular organisms exhibit a high heterogeneous repertoire of vesicles which current methods based on ensemble measurements cannot capture. In this work we present droplet barcode sequencing for protein analysis (DBS-Pro) to profile surface proteins on individual sEVs, facilitating identification of sEV-subtypes within and between samples. The method allows for analysis of multiple proteins through use of DNA barcoded affinity reagents and sequencing as readout. High throughput single vesicle profiling is enabled through compartmentalization of individual sEVs in emulsion droplets followed by droplet barcoding through PCR. In this proof-of-concept study we demonstrate that DBS-Pro allows for analysis of single sEVs, with a mixing rate below 2%. A total of over 120,000 individual sEVs obtained from a NSCLC cell line and from malignant pleural effusion (MPE) fluid of NSCLC patients have been analyzed based on their surface proteins. We also show that the method enables single vesicle surface protein profiling and by extension characterization of sEV-subtypes, which is essential to identify the cellular origin of vesicles in heterogenous samples.}, } @article {pmid36305297, year = {2022}, author = {León-Ruiz, JA and Cruz Ramírez, A}, title = {Predicted landscape of RETINOBLASTOMA-RELATED LxCxE-mediated interactions across the Chloroplastida.}, journal = {The Plant journal : for cell and molecular biology}, volume = {112}, number = {6}, pages = {1507-1524}, doi = {10.1111/tpj.16012}, pmid = {36305297}, issn = {1365-313X}, mesh = {Animals ; *Retinoblastoma ; Retinoblastoma Protein/metabolism ; Cell Differentiation ; *Retinal Neoplasms ; }, abstract = {The colonization of land by a single streptophyte algae lineage some 450 million years ago has been linked to multiple key innovations such as three-dimensional growth, alternation of generations, the presence of stomata, as well as innovations inherent to the birth of major plant lineages, such as the origins of vascular tissues, roots, seeds and flowers. Multicellularity, which evolved multiple times in the Chloroplastida coupled with precise spatiotemporal control of proliferation and differentiation were instrumental for the evolution of these traits. RETINOBLASTOMA-RELATED (RBR), the plant homolog of the metazoan Retinoblastoma protein (pRB), is a highly conserved and multifunctional core cell cycle regulator that has been implicated in the evolution of multicellularity in the green lineage as well as in plant multicellularity-related processes such as proliferation, differentiation, stem cell regulation and asymmetric cell division. RBR fulfills these roles through context-specific protein-protein interactions with proteins containing the Leu-x-Cys-x-Glu (LxCxE) short-linear motif (SLiM); however, how RBR-LxCxE interactions have changed throughout major innovations in the Viridiplantae kingdom is a question that remains unexplored. Here, we employ an in silico evo-devo approach to predict and analyze potential RBR-LxCxE interactions in different representative species of key Chloroplastida lineages, providing a valuable resource for deciphering RBR-LxCxE multiple functions. Furthermore, our analyses suggest that RBR-LxCxE interactions are an important component of RBR functions and that interactions with chromatin modifiers/remodelers, DNA replication and repair machinery are highly conserved throughout the Viridiplantae, while LxCxE interactions with transcriptional regulators likely diversified throughout the water-to-land transition.}, } @article {pmid36283350, year = {2022}, author = {Keller, J and Delaux, PM}, title = {Plant phylogenetics: The never-ending cycle of evolutionary gains and losses.}, journal = {Current biology : CB}, volume = {32}, number = {20}, pages = {R1028-R1029}, doi = {10.1016/j.cub.2022.09.006}, pmid = {36283350}, issn = {1879-0445}, mesh = {*Embryophyta ; Phylogeny ; Plants/genetics ; Evolution, Molecular ; Biological Evolution ; }, abstract = {The Zygnematophyceae is the sister clade to the land plants, but their biology remains mysterious. In a new study, a resolved phylogeny and a scenario for the evolution of multicellularity in that clade are proposed.}, } @article {pmid36264199, year = {2022}, author = {Whye, D and Wood, D and Kim, KH and Chen, C and Makhortova, N and Sahin, M and Buttermore, ED}, title = {Dynamic 3D Combinatorial Generation of hPSC-Derived Neuromesodermal Organoids With Diverse Regional and Cellular Identities.}, journal = {Current protocols}, volume = {2}, number = {10}, pages = {e568}, pmid = {36264199}, issn = {2691-1299}, support = {P50 HD105351/HD/NICHD NIH HHS/United States ; }, mesh = {Humans ; Pregnancy ; Female ; *Organoids ; Hedgehog Proteins ; Poloxamer ; *Pluripotent Stem Cells ; Fibroblast Growth Factors ; Retinoids ; }, abstract = {Neuromesodermal progenitors represent a unique, bipotent population of progenitors residing in the tail bud of the developing embryo, which give rise to the caudal spinal cord cell types of neuroectodermal lineage as well as the adjacent paraxial somite cell types of mesodermal origin. With the advent of stem cell technologies, including induced pluripotent stem cells (iPSCs), the modeling of rare genetic disorders can be accomplished in vitro to interrogate cell-type specific pathological mechanisms in human patient conditions. Stem cell-derived models of neuromesodermal progenitors have been accomplished by several developmental biology groups; however, most employ a 2D monolayer format that does not fully reflect the complexity of cellular differentiation in the developing embryo. This article presents a dynamic 3D combinatorial method to generate robust populations of human pluripotent stem cell-derived neuromesodermal organoids with multi-cellular fates and regional identities. By utilizing a dynamic 3D suspension format for the differentiation process, the organoids differentiated by following this protocol display a hallmark of embryonic development that involves a morphological elongation known as axial extension. Furthermore, by employing a combinatorial screening assay, we dissect essential pathways for optimally directing the patterning of pluripotent stem cells into neuromesodermal organoids. This protocol highlights the influence of timing, duration, and concentration of WNT and fibroblast growth factor (FGF) signaling pathways on enhancing early neuromesodermal identity, and later, downstream cell fate specification through combined synergies of retinoid signaling and sonic hedgehog activation. Finally, through robust inhibition of the Notch signaling pathway, this protocol accelerates the acquisition of terminal cell identities. This enhanced organoid model can serve as a powerful tool for studying normal developmental processes as well as investigating complex neurodevelopmental disorders, such as neural tube defects. © 2022 Wiley Periodicals LLC. Basic Protocol 1: Robust generation of 3D hPSC-derived spheroid populations in dynamic motion settings Support Protocol 1: Pluronic F-127 reagent preparation and coating to generate low-attachment suspension culture dishes Basic Protocol 2: Enhanced specification of hPSCs into NMP organoids Support Protocol 2: Combinatorial pathway assay for NMP organoid protocol optimization Basic Protocol 3: Differentiation of NMP organoids along diverse cellular trajectories and accelerated terminal fate specification into neurons, neural crest, and sclerotome derivatives.}, } @article {pmid36255595, year = {2022}, author = {Bano, N and Aalam, S and Bag, SK}, title = {Tubby-like proteins (TLPs) transcription factor in different regulatory mechanism in plants: a review.}, journal = {Plant molecular biology}, volume = {110}, number = {6}, pages = {455-468}, pmid = {36255595}, issn = {1573-5028}, mesh = {Animals ; *Transcription Factors/genetics/metabolism ; Amino Acid Sequence ; *Plants/genetics/metabolism ; Stress, Physiological ; Plant Growth Regulators/metabolism ; }, abstract = {Tubby-like proteins (TLPs) transcription factors are found in single-celled to multi-cellular eukaryotes in the form of large multigene families. TLPs are identified through a specific signature of carboxyl terminal tubby domain, required for plasma membrane tethering and amino terminal F-box domain communicate as functional SCF-type E3 ligases. The comprehensive distribution of TLP gene family members in diverse species indicates some conserved functions of TLPs in multicellular organisms. Plant TLPs have higher gene members than animals and these members reported important role in multiple physiological and developmental processes and various environmental stress responses. Although the TLPs are suggested to be a putative transcription factors but their functional mechanism is not much clear. This review provides significant recent updates on TLP-mediated regulation with an insight into its functional roles, origin and evolution and also phytohormones related regulation to combat with various stresses and its involvement in adaptive stress response in crop plants.}, } @article {pmid36252029, year = {2022}, author = {Günther, M and Reimer, C and Herbst, R and Kufs, JE and Rautschek, J and Ueberschaar, N and Zhang, S and Peschel, G and Reimer, L and Regestein, L and Valiante, V and Hillmann, F and Stallforth, P}, title = {Yellow polyketide pigment suppresses premature hatching in social amoeba.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {119}, number = {43}, pages = {e2116122119}, pmid = {36252029}, issn = {1091-6490}, mesh = {*Amoeba/genetics ; *Biological Products/metabolism ; *Dictyostelium/physiology ; Polyketide Synthases/genetics/metabolism ; *Polyketides/metabolism ; }, abstract = {Low-molecular-weight natural products from microbes are indispensable in the development of potent drugs. However, their biological roles within an ecological context often remain elusive. Here, we shed light on natural products from eukaryotic microorganisms that have the ability to transition from single cells to multicellular organisms: the social amoebae. These eukaryotes harbor a large number of polyketide biosynthetic genes in their genomes, yet virtually none of the corresponding products can be isolated or characterized. Using complementary molecular biology approaches, including CRISPR-Cas9, we generated polyketide synthase (pks5) inactivation and overproduction strains of the social amoeba Dictyostelium discoideum. Differential, untargeted metabolomics of wild-type versus mutant fruiting bodies allowed us to pinpoint candidate metabolites derived from the amoebal PKS5. Extrachromosomal expression of the respective gene led to the identification of a yellow polyunsaturated fatty acid. Analysis of the temporospatial production pattern of this compound in conjunction with detailed bioactivity studies revealed the polyketide to be a spore germination suppressor.}, } @article {pmid36237424, year = {2022}, author = {Kumar, P and Kumar, P and Mandal, D and Velayutham, R}, title = {The emerging role of Deubiquitinases (DUBs) in parasites: A foresight review.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {985178}, pmid = {36237424}, issn = {2235-2988}, mesh = {Adenosine Triphosphate/metabolism ; Amino Acids/metabolism ; Animals ; Antiparasitic Agents ; Caspases/metabolism ; *Cryptosporidiosis ; *Cryptosporidium ; Deubiquitinating Enzymes/genetics/metabolism ; Humans ; *Parasites/metabolism ; Phylogeny ; Polyubiquitin/genetics/metabolism ; Proteasome Endopeptidase Complex/metabolism ; Ubiquitin/metabolism ; Ubiquitination ; }, abstract = {Before the discovery of the proteasome complex, the lysosomes with acidic proteases and caspases in apoptotic pathways were thought to be the only pathways for the degradation of damaged, unfolded, and aged proteins. However, the discovery of 26S and 20S proteasome complexes in eukaryotes and microbes, respectively, established that the degradation of most proteins is a highly regulated ATP-dependent pathway that is significantly conserved across each domain of life. The proteasome is part of the ubiquitin-proteasome system (UPS), where the covalent tagging of a small molecule called ubiquitin (Ub) on the proteins marks its proteasomal degradation. The type and chain length of ubiquitination further determine whether a protein is designated for further roles in multi-cellular processes like DNA repair, trafficking, signal transduction, etc., or whether it will be degraded by the proteasome to recycle the peptides and amino acids. Deubiquitination, on the contrary, is the removal of ubiquitin from its substrate molecule or the conversion of polyubiquitin chains into monoubiquitin as a precursor to ubiquitin. Therefore, deubiquitylating enzymes (DUBs) can maintain the dynamic state of cellular ubiquitination by releasing conjugated ubiquitin from proteins and controlling many cellular pathways that are essential for their survival. Many DUBs are well characterized in the human system with potential drug targets in different cancers. Although, proteasome complex and UPS of parasites, like plasmodium and leishmania, were recently coined as multi-stage drug targets the role of DUBs is completely unexplored even though structural domains and functions of many of these parasite DUBs are conserved having high similarity even with its eukaryotic counterpart. This review summarizes the identification & characterization of different parasite DUBs based on in silico and a few functional studies among different phylogenetic classes of parasites including Metazoan (Schistosoma, Trichinella), Apicomplexan protozoans (Plasmodium, Toxoplasma, Eimeria, Cryptosporidium), Kinetoplastidie (Leishmania, Trypanosoma) and Microsporidia (Nosema). The identification of different homologs of parasite DUBs with structurally similar domains with eukaryotes, and the role of these DUBs alone or in combination with the 20S proteosome complex in regulating the parasite survival/death is further elaborated. We propose that small molecules/inhibitors of human DUBs can be potential antiparasitic agents due to their significant structural conservation.}, } @article {pmid36232785, year = {2022}, author = {Vinogradov, AE and Anatskaya, OV}, title = {Cellular Biogenetic Law and Its Distortion by Protein Interactions: A Possible Unified Framework for Cancer Biology and Regenerative Medicine.}, journal = {International journal of molecular sciences}, volume = {23}, number = {19}, pages = {}, pmid = {36232785}, issn = {1422-0067}, mesh = {Animals ; Biology ; Cell Differentiation/genetics ; Embryonic Stem Cells ; Humans ; *Induced Pluripotent Stem Cells ; *Neoplasms/genetics/metabolism ; Regenerative Medicine ; }, abstract = {The biogenetic law (recapitulation law) states that ontogenesis recapitulates phylogenesis. However, this law can be distorted by the modification of development. We showed the recapitulation of phylogenesis during the differentiation of various cell types, using a meta-analysis of human single-cell transcriptomes, with the control for cell cycle activity and the improved phylostratigraphy (gene dating). The multipotent progenitors, differentiated from pluripotent embryonic stem cells (ESC), showed the downregulation of unicellular (UC) genes and the upregulation of multicellular (MC) genes, but only in the case of those originating up to the Euteleostomi (bony vertebrates). This picture strikingly resembles the evolutionary profile of regulatory gene expansion due to gene duplication in the human genome. The recapitulation of phylogenesis in the induced pluripotent stem cells (iPSC) during their differentiation resembles the ESC pattern. The unipotent erythroblasts differentiating into erythrocytes showed the downregulation of UC genes and the upregulation of MC genes originating after the Euteleostomi. The MC interactome neighborhood of a protein encoded by a UC gene reverses the gene expression pattern. The functional analysis showed that the evolved environment of the UC proteins is typical for protein modifiers and signaling-related proteins. Besides a fundamental aspect, this approach can provide a unified framework for cancer biology and regenerative/rejuvenation medicine because oncogenesis can be defined as an atavistic reversal to a UC state, while regeneration and rejuvenation require an ontogenetic reversal.}, } @article {pmid36218381, year = {2022}, author = {Silva, VSD and Machado, CR}, title = {Sex in protists: A new perspective on the reproduction mechanisms of trypanosomatids.}, journal = {Genetics and molecular biology}, volume = {45}, number = {3}, pages = {e20220065}, pmid = {36218381}, issn = {1415-4757}, abstract = {The Protist kingdom individuals are the most ancestral representatives of eukaryotes. They have inhabited Earth since ancient times and are currently found in the most diverse environments presenting a great heterogeneity of life forms. The unicellular and multicellular algae, photosynthetic and heterotrophic organisms, as well as free-living and pathogenic protozoa represents the protist group. The evolution of sex is directly associated with the origin of eukaryotes being protists the earliest protagonists of sexual reproduction on earth. In eukaryotes, the recombination through genetic exchange is a ubiquitous mechanism that can be stimulated by DNA damage. Scientific evidences support the hypothesis that reactive oxygen species (ROS) induced DNA damage can promote sexual recombination in eukaryotes which might have been a decisive factor for the origin of sex. The fact that some recombination enzymes also participate in meiotic sex in modern eukaryotes reinforces the idea that sexual reproduction emerged as consequence of specific mechanisms to cope with mutations and alterations in genetic material. In this review we will discuss about origin of sex and different strategies of evolve sexual reproduction in some protists such that cause human diseases like malaria, toxoplasmosis, sleeping sickness, Chagas disease, and leishmaniasis.}, } @article {pmid36202151, year = {2022}, author = {Wang, P and Chen, C and Wang, Q and Chen, H and Chen, C and Xu, J and Wang, X and Song, T}, title = {Tumor inhibition via magneto-mechanical oscillation by magnetotactic bacteria under a swing MF.}, journal = {Journal of controlled release : official journal of the Controlled Release Society}, volume = {351}, number = {}, pages = {941-953}, doi = {10.1016/j.jconrel.2022.09.059}, pmid = {36202151}, issn = {1873-4995}, mesh = {Animals ; *Magnetosomes/metabolism ; Gram-Negative Bacteria ; Bacteria/metabolism ; Magnetics ; Mammals ; }, abstract = {Since magnetic micro/nano-materials can serve as multifunctional transducers for remote control of cell functions by applying diverse magnetic fields, magnetic cell manipulation provides a highly promising tool in biomedical research encompassing neuromodulation, tissue regeneration engineering and tumor cell destruction. Magnetotactic bacteria (MTB), which contain natural magnetic materials, can sensitively respond to external magnetic fields via their endogenous magnetosome chains. Here, we developed a technique for magnetotactic bacteria-based cell modulation and tumor suppression combined with a swing magnetic field. We enabled MTB cells to recognize and bind to mammalian tumor cells via functional modification with RGD peptides onto the surfaces of MTB cells, and RGD-modified MTB bacteria could interact with the targeted tumor cells effectively. The magnetic torque, which was due to the interaction of the long magnetosome chain inside the MTB bacterial cell and the applied swing magnetic field, could result in obvious swing magnetic behaviors of the modified MTB bacteria bound to tumor cell surfaces and thus subsequently exert a sustained magnetomechanical oscillation on the tumor cell surfaces, which could induce a significant activation of Ca[2+] ion influx in vitro and tumor growth inhibition in vivo. These findings suggest that MTB cells mediated magnetomechanical stimulation, which is remotely controlled by dynamic magnetic fields, as an effective way to regulate cell signaling and treat tumor growth, which will shed the light on further biomedical applications utilizing whole magnetotactic bacteria.}, } @article {pmid36198374, year = {2022}, author = {Grunt, TW and Valent, P}, title = {Cancer - A devastating disease, but also an eye-opener and window into the deep mysteries of life and its origins.}, journal = {Progress in biophysics and molecular biology}, volume = {175}, number = {}, pages = {131-139}, doi = {10.1016/j.pbiomolbio.2022.09.009}, pmid = {36198374}, issn = {1873-1732}, mesh = {Humans ; *Biological Evolution ; Thermodynamics ; Entropy ; *Neoplasms ; Mutation ; }, abstract = {Although cancer is still the second leading cause of death worldwide, basic research has largely elucidated the underlying mechanisms that lead us deep into the laws of animate and inanimate nature. This review aims to demonstrate that the cancer process profoundly affects and reprograms fundamental principles and concepts of cellular life by harnessing the natural mechanisms of biological evolution. It is shown that mutation and selection - the drivers of cancer formation and progression - are mandatory consequences of Boltzmann's version of the second law of thermodynamics, which stipulates that entropy (or disorder) according to probability never decreases, followed by Darwinian evolution by filtering for the suitable geno- and karyotypes. Cancer research has shown that malignant cells can develop gradually or abruptly depending on the prevailing stress conditions. Similar principles were then observed in the evolution of species, referred to as micro- and macroevolution. Cancer cells can be related to phylogenetically older forms of life, and malignant transformation can be viewed as reverse (atavistic) evolution, accompanied by typical rearrangement of system information and loss of 'social' behavior. It becomes obvious that in nature no distinction is made between normal biology and pathobiology. Instead, everything follows the rules of natural evolution. This illustrates the depth of the cancer problem and may explain the serious difficulties faced in trying to eradicate cancer.}, } @article {pmid36196535, year = {2022}, author = {Gauthier, AE and Rotjan, RD and Kagan, JC}, title = {Lipopolysaccharide detection by the innate immune system may be an uncommon defence strategy used in nature.}, journal = {Open biology}, volume = {12}, number = {10}, pages = {220146}, pmid = {36196535}, issn = {2046-2441}, mesh = {Animals ; Immune System/metabolism ; Immunity, Innate ; *Lipopolysaccharides ; Mammals ; *Pathogen-Associated Molecular Pattern Molecules ; }, abstract = {Since the publication of the Janeway's Pattern Recognition hypothesis in 1989, study of pathogen-associated molecular patterns (PAMPs) and their immuno-stimulatory activities has accelerated. Most studies in this area have been conducted in model organisms, which leaves many open questions about the universality of PAMP biology across living systems. Mammals have evolved multiple proteins that operate as receptors for the PAMP lipopolysaccharide (LPS) from Gram-negative bacteria, but LPS is not immuno-stimulatory in all eukaryotes. In this review, we examine the history of LPS as a PAMP in mammals, recent data on LPS structure and its ability to activate mammalian innate immune receptors, and how these activities compare across commonly studied eukaryotes. We discuss why LPS may have evolved to be immuno-stimulatory in some eukaryotes but not others and propose two hypotheses about the evolution of PAMP structure based on the ecology and environmental context of the organism in question. Understanding PAMP structures and stimulatory mechanisms across multi-cellular life will provide insights into the evolutionary origins of innate immunity and may lead to the discovery of new PAMP variations of scientific and therapeutic interest.}, } @article {pmid36180988, year = {2022}, author = {Turishcheva, E and Vildanova, M and Onishchenko, G and Smirnova, E}, title = {The Role of Endoplasmic Reticulum Stress in Differentiation of Cells of Mesenchymal Origin.}, journal = {Biochemistry. Biokhimiia}, volume = {87}, number = {9}, pages = {916-931}, pmid = {36180988}, issn = {1608-3040}, mesh = {*COVID-19 ; Cell Differentiation ; *Endoplasmic Reticulum Stress ; Fibrosis ; Humans ; Unfolded Protein Response ; }, abstract = {Endoplasmic reticulum (ER) is a multifunctional membrane-enclosed organelle. One of the major ER functions is cotranslational transport and processing of secretory, lysosomal, and transmembrane proteins. Impaired protein processing caused by disturbances in the ER homeostasis results in the ER stress. Restoration of normal ER functioning requires activation of an adaptive mechanism involving cell response to misfolded proteins, the so-called unfolded protein response (UPR). Besides controlling protein folding, UPR plays a key role in other physiological processes, in particular, differentiation of cells of connective, muscle, epithelial, and neural tissues. Cell differentiation is induced by the physiological levels of ER stress, while excessive ER stress suppresses differentiation and can result in cell death. So far, it remains unknown whether UPR activation induces cell differentiation or if UPR is initiated by the upregulated synthesis of secretory proteins during cell differentiation. Cell differentiation is an important stage in the development of multicellular organisms and is tightly controlled. Suppression or excessive activation of this process can lead to the development of various pathologies in an organism. In particular, impairments in the differentiation of connective tissue cells can result in the development of fibrosis, obesity, and osteoporosis. Recently, special attention has been paid to fibrosis as one of the major complications of COVID-19. Therefore, studying the role of UPR in the activation of cell differentiation is of both theoretical and practical interest, as it might result in the identification of molecular targets for selective regulation of cell differentiation stages and as well as the potential to modulate the mechanisms involved in the development of various pathological states.}, } @article {pmid36127662, year = {2022}, author = {Chai, S and Aria, C and Hua, H}, title = {A stem group Codium alga from the latest Ediacaran of South China provides taxonomic insight into the early diversification of the plant kingdom.}, journal = {BMC biology}, volume = {20}, number = {1}, pages = {199}, pmid = {36127662}, issn = {1741-7007}, mesh = {Animals ; China ; *Chlorophyta/genetics ; *Ecosystem ; Eukaryotic Cells ; Fossils ; }, abstract = {BACKGROUND: In recent years, Precambrian lifeforms have generated an ever-increasing interest because they revealed a rich eukaryotic diversity prior to the Cambrian explosion of modern animals. Among them, macroalgae are known to be a conspicuous component of Neoproterozoic ecosystems, and chlorophytes in particular are already documented in the Tonian, when they were so far expected to originate. However, like for other major eukaryotic lineages, and despite predictions of molecular clock analyses placing roots of these lineages well into the Neoproterozoic, a taxonomic constraint on Precambrian green algae has remained difficult.

RESULTS: Here, we present an exceptionally preserved spherical, coenocytic unicellular alga from the latest Ediacaran Dengying Formation of South China (> ca. 541 Ma), known from both external and internal morphology, fully tridimensional and in great detail. Tomographic X-ray and electronic microscopy revealed a characteristic medulla made of intertwined siphons and tightly packed peripheral utricles, suggesting these fossils belong to the Bryopsidales genus Codium. However, its distinctly smaller size compared to extant species leads us to create Protocodium sinense gen. et sp. nov. and a phylomorphospace investigation points to a possible stem group affinity.

CONCLUSIONS: Our finding has several important implications. First, Protocodium allows for a more precise calibration of Archaeplastida and directly confirms that a group as derived as Ulvophyceae was already well diversified in various ecosystems prior to the Cambrian explosion. Details of tridimensional morphology also invite a reassessment of the identification of other Ediacaran algae, such as Chuaria, to better discriminate mono-versus multicellularity, and suggest unicellular Codium-like morphotypes could be much older and widespread. More broadly, Protocodium provides insights into the early diversification of the plant kingdom, the composition of Precambrian ecosystems, and the extreme longevity of certain eukaryotic plans of organization.}, } @article {pmid36114258, year = {2022}, author = {La Fortezza, M and Rendueles, O and Keller, H and Velicer, GJ}, title = {Hidden paths to endless forms most wonderful: ecology latently shapes evolution of multicellular development in predatory bacteria.}, journal = {Communications biology}, volume = {5}, number = {1}, pages = {977}, pmid = {36114258}, issn = {2399-3642}, mesh = {Agar ; Animals ; *Myxococcus xanthus/genetics ; Phenotype ; *Predatory Behavior ; }, abstract = {Ecological causes of developmental evolution, for example from predation, remain much investigated, but the potential importance of latent phenotypes in eco-evo-devo has received little attention. Using the predatory bacterium Myxococcus xanthus, which undergoes aggregative fruiting body development upon starvation, we tested whether adaptation to distinct growth environments that do not induce development latently alters developmental phenotypes under starvation conditions that do induce development. In an evolution experiment named MyxoEE-3, growing M. xanthus populations swarmed across agar surfaces while adapting to conditions varying at factors such as surface stiffness or prey identity. Such ecological variation during growth was found to greatly impact the latent evolution of development, including fruiting body morphology, the degree of morphological trait correlation, reaction norms, degrees of developmental plasticity and stochastic diversification. For example, some prey environments promoted retention of developmental proficiency whereas others led to its systematic loss. Our results have implications for understanding evolutionary interactions among predation, development and motility in myxobacterial life cycles, and, more broadly, how ecology can profoundly shape the evolution of developmental systems latently rather than by direct selection on developmental features.}, } @article {pmid36102042, year = {2022}, author = {Xie, Q and Xiong, C and Yang, Q and Zheng, F and Larkin, RM and Zhang, J and Wang, T and Zhang, Y and Ouyang, B and Lu, Y and Ye, J and Ye, Z and Yang, C}, title = {A novel regulatory complex mediated by Lanata (Ln) controls multicellular trichome formation in tomato.}, journal = {The New phytologist}, volume = {236}, number = {6}, pages = {2294-2310}, doi = {10.1111/nph.18492}, pmid = {36102042}, issn = {1469-8137}, mesh = {*Trichomes/metabolism ; *Solanum lycopersicum/genetics/metabolism ; Gene Expression Regulation, Plant ; Plant Proteins/genetics/metabolism ; Plant Epidermis/metabolism ; }, abstract = {Trichomes that originate from plant aerial epidermis act as mechanical and chemical barriers against herbivores. Although several regulators have recently been identified, the regulatory pathway underlying multicellular trichome formation remains largely unknown in tomato. Here, we report a novel HD-ZIP IV transcription factor, Lanata (Ln), a missense mutation which caused the hairy phenotype. Biochemical analyses demonstrate that Ln separately interacts with two trichome regulators, Woolly (Wo) and Hair (H). Genetic and molecular evidence demonstrates that Ln directly regulates the expression of H. The interaction between Ln and Wo can increase trichome density by enhancing the expression of SlCycB2 and SlCycB3, which we previously showed are involved in tomato trichome formation. Furthermore, SlCycB2 represses the transactivation of the SlCycB3 gene by Ln and vice versa. Our findings provide new insights into the novel regulatory network controlling multicellular trichome formation in tomato.}, } @article {pmid36099169, year = {2022}, author = {Ress, V and Traulsen, A and Pichugin, Y}, title = {Eco-evolutionary dynamics of clonal multicellular life cycles.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {36099169}, issn = {2050-084X}, mesh = {Animals ; *Biological Evolution ; *Life Cycle Stages ; Models, Theoretical ; }, abstract = {The evolution of multicellular life cycles is a central process in the course of the emergence of multicellularity. The simplest multicellular life cycle is comprised of the growth of the propagule into a colony and its fragmentation to give rise to new propagules. The majority of theoretical models assume selection among life cycles to be driven by internal properties of multicellular groups, resulting in growth competition. At the same time, the influence of interactions between groups on the evolution of life cycles is rarely even considered. Here, we present a model of colonial life cycle evolution taking into account group interactions. Our work shows that the outcome of evolution could be coexistence between multiple life cycles or that the outcome may depend on the initial state of the population - scenarios impossible without group interactions. At the same time, we found that some results of these simpler models remain relevant: evolutionary stable strategies in our model are restricted to binary fragmentation - the same class of life cycles that contains all evolutionarily optimal life cycles in the model without interactions. Our results demonstrate that while models neglecting interactions can capture short-term dynamics, they fall short in predicting the population-scale picture of evolution.}, } @article {pmid36098425, year = {2022}, author = {Noh, S and Capodanno, BJ and Xu, S and Hamilton, MC and Strassmann, JE and Queller, DC}, title = {Reduced and Nonreduced Genomes in Paraburkholderia Symbionts of Social Amoebas.}, journal = {mSystems}, volume = {7}, number = {5}, pages = {e0056222}, pmid = {36098425}, issn = {2379-5077}, mesh = {Animals ; *Amoeba/microbiology ; *Dictyostelium/genetics ; Eukaryota ; *Burkholderiaceae/genetics ; Bacteria/genetics ; Soil ; }, abstract = {The social amoeba Dictyostelium discoideum is a predatory soil protist frequently used for studying host-pathogen interactions. A subset of D. discoideum strains isolated from soil persistently carry symbiotic Paraburkholderia, recently formally described as P. agricolaris, P. bonniea, and P. hayleyella. The three facultative symbiont species of D. discoideum present a unique opportunity to study a naturally occurring symbiosis in a laboratory model protist. There is a large difference in genome size between P. agricolaris (8.7 million base pairs [Mbp]) versus P. hayleyella and P. bonniea (4.1 Mbp). We took a comparative genomics approach and compared the three genomes of D. discoideum symbionts to 12 additional Paraburkholderia genomes to test for genome evolution patterns that frequently accompany host adaptation. Overall, P. agricolaris is difficult to distinguish from other Paraburkholderia based on its genome size and content, but the reduced genomes of P. bonniea and P. hayleyella display characteristics indicative of genome streamlining rather than deterioration during adaptation to their protist hosts. In addition, D. discoideum-symbiont genomes have increased secretion system and motility genes that may mediate interactions with their host. Specifically, adjacent BurBor-like type 3 and T6SS-5-like type 6 secretion system operons shared among all three D. discoideum-symbiont genomes may be important for host interaction. Horizontal transfer of these secretion system operons within the amoeba host environment may have contributed to the unique ability of these symbionts to establish and maintain a symbiotic relationship with D. discoideum. IMPORTANCE Protists are a diverse group of typically single cell eukaryotes. Bacteria and archaea that form long-term symbiotic relationships with protists may evolve in additional ways than those in relationships with multicellular eukaryotes such as plants, animals, or fungi. Social amoebas are a predatory soil protist sometimes found with symbiotic bacteria living inside their cells. They present a unique opportunity to explore a naturally occurring symbiosis in a protist frequently used for studying host-pathogen interactions. We show that one amoeba-symbiont species is similar to other related bacteria in genome size and content, while the two reduced-genome-symbiont species show characteristics of genome streamlining rather than deterioration during adaptation to their host. We also identify sets of genes present in all three amoeba-symbiont genomes that are potentially used for host-symbiont interactions. Because the amoeba symbionts are distantly related, the amoeba host environment may be where these genes were shared among symbionts.}, } @article {pmid36077092, year = {2022}, author = {Anatskaya, OV and Vinogradov, AE}, title = {Polyploidy and Myc Proto-Oncogenes Promote Stress Adaptation via Epigenetic Plasticity and Gene Regulatory Network Rewiring.}, journal = {International journal of molecular sciences}, volume = {23}, number = {17}, pages = {}, pmid = {36077092}, issn = {1422-0067}, mesh = {Chromatin ; Epigenesis, Genetic ; *Gene Regulatory Networks ; Humans ; *Polyploidy ; Proto-Oncogenes ; }, abstract = {Polyploid cells demonstrate biological plasticity and stress adaptation in evolution; development; and pathologies, including cardiovascular diseases, neurodegeneration, and cancer. The nature of ploidy-related advantages is still not completely understood. Here, we summarize the literature on molecular mechanisms underlying ploidy-related adaptive features. Polyploidy can regulate gene expression via chromatin opening, reawakening ancient evolutionary programs of embryonality. Chromatin opening switches on genes with bivalent chromatin domains that promote adaptation via rapid induction in response to signals of stress or morphogenesis. Therefore, stress-associated polyploidy can activate Myc proto-oncogenes, which further promote chromatin opening. Moreover, Myc proto-oncogenes can trigger polyploidization de novo and accelerate genome accumulation in already polyploid cells. As a result of these cooperative effects, polyploidy can increase the ability of cells to search for adaptive states of cellular programs through gene regulatory network rewiring. This ability is manifested in epigenetic plasticity associated with traits of stemness, unicellularity, flexible energy metabolism, and a complex system of DNA damage protection, combining primitive error-prone unicellular repair pathways, advanced error-free multicellular repair pathways, and DNA damage-buffering ability. These three features can be considered important components of the increased adaptability of polyploid cells. The evidence presented here contribute to the understanding of the nature of stress resistance associated with ploidy and may be useful in the development of new methods for the prevention and treatment of cardiovascular and oncological diseases.}, } @article {pmid36076976, year = {2022}, author = {Burzacka-Hinz, A and Narajczyk, M and Dudek, M and Szlachetko, DL}, title = {Micromorphology of Labellum in Selected Dendrobium Sw. (Orchidaceae, Dendrobieae).}, journal = {International journal of molecular sciences}, volume = {23}, number = {17}, pages = {}, pmid = {36076976}, issn = {1422-0067}, mesh = {*Dendrobium ; Flowers/anatomy & histology ; Microscopy, Electron, Scanning ; *Orchidaceae/anatomy & histology ; Phylogeny ; Trichomes ; }, abstract = {Dendrobium is one of the most species-rich genera of the Paleotropical orchids. It embraces more than 1000 species, most of which are epiphytes. The strong variation in floral characters causes many identification difficulties within this genus. One of the key structures, often sufficient in identification on a species level, is the labellum, which in many species of Dendrobium possesses a thickened callus and various types of trichomes and papillae. The aim of this study is to identify and describe the structures present on the labellum surface of the analyzed species, determine their distribution and density, as well as to check whether the obtained data have taxonomic value. In this paper, we present the results of a micromorphological study on the labellum of 21 species of Dendrobium, representing 13 sections, using scanning electron microscopy (SEM). Our studies revealed the presence of both uni- and multicellular structures on the surface of the labellum. We observed three types of trichomes (conical, cylindrical, ellipsoidal) and three types of papillae (conical, cylindrical, semicircular). Neither trichomes nor papillae were recorded for five species. In addition, we made diagrams showing the distribution and density of structures on the labellum. Based on the micromorphological results combined with the phylogenetic tree performed, we suggest that the presence/absence of labellum structures does not necessarily reflect the phylogenetic relationship and might be misleading, as in some cases, they arise due to convergence.}, } @article {pmid36055238, year = {2022}, author = {Hess, S and Williams, SK and Busch, A and Irisarri, I and Delwiche, CF and de Vries, S and Darienko, T and Roger, AJ and Archibald, JM and Buschmann, H and von Schwartzenberg, K and de Vries, J}, title = {A phylogenomically informed five-order system for the closest relatives of land plants.}, journal = {Current biology : CB}, volume = {32}, number = {20}, pages = {4473-4482.e7}, pmid = {36055238}, issn = {1879-0445}, mesh = {Phylogeny ; Biological Evolution ; *Embryophyta/genetics ; *Charophyceae/genetics ; *Streptophyta ; Plants ; Soil ; }, abstract = {The evolution of streptophytes had a profound impact on life on Earth. They brought forth those photosynthetic eukaryotes that today dominate the macroscopic flora: the land plants (Embryophyta).[1] There is convincing evidence that the unicellular/filamentous Zygnematophyceae-and not the morphologically more elaborate Coleochaetophyceae or Charophyceae-are the closest algal relatives of land plants.[2-6] Despite the species richness (>4,000), wide distribution, and key evolutionary position of the zygnematophytes, their internal phylogeny remains largely unresolved.[7,8] There are also putative zygnematophytes with interesting body plan modifications (e.g., filamentous growth) whose phylogenetic affiliations remain unknown. Here, we studied a filamentous green alga (strain MZCH580) from an Austrian peat bog with central or parietal chloroplasts that lack discernible pyrenoids. It represents Mougeotiopsis calospora PALLA, an enigmatic alga that was described more than 120 years ago[9] but never subjected to molecular analyses. We generated transcriptomic data of M. calospora strain MZCH580 and conducted comprehensive phylogenomic analyses (326 nuclear loci) for 46 taxonomically diverse zygnematophytes. Strain MZCH580 falls in a deep-branching zygnematophycean clade together with some unicellular species and thus represents a formerly unknown zygnematophycean lineage with filamentous growth. Our well-supported phylogenomic tree lets us propose a new five-order system for the Zygnematophyceae and provides evidence for at least five independent origins of true filamentous growth in the closest algal relatives of land plants. This phylogeny provides a robust and comprehensive framework for performing comparative analyses and inferring the evolution of cellular traits and body plans in the closest relatives of land plants.}, } @article {pmid36045216, year = {2022}, author = {Michla, M and Wilhelm, C}, title = {Food for thought - ILC metabolism in the context of helminth infections.}, journal = {Mucosal immunology}, volume = {15}, number = {6}, pages = {1234-1242}, pmid = {36045216}, issn = {1935-3456}, mesh = {Animals ; Humans ; Immunity, Innate ; Lymphocytes ; *Helminthiasis ; *Helminths ; Inflammation ; }, abstract = {Helminths are multicellular ancient organisms residing as parasites at mucosal surfaces of their host. Through adaptation and co-evolution with their hosts, helminths have been able to develop tolerance mechanisms to limit inflammation and avoid expulsion. The study of helminth infections as an integral part of tissue immunology allowed us to understand fundamental aspects of mucosal and barrier immunology, which led to the discovery of a new group of tissue-resident immune cells, innate lymphoid cells (ILC), over a decade ago. Here, we review the intricate interplay between helminth infections and type 2 ILC (ILC2) biology, discuss the host metabolic adaptation to helminth infections and the metabolic pathways fueling ILC2 responses. We hypothesize that nutrient competition between host and helminths may have prevented chronic inflammation in the past and argue that a detailed understanding of the metabolic restraints imposed by helminth infections may offer new therapeutic avenues in the future.}, } @article {pmid36028058, year = {2022}, author = {Senthilkumar, I and Howley, E and McEvoy, E}, title = {Thermodynamically-motivated chemo-mechanical models and multicellular simulation to provide new insight into active cell and tumour remodelling.}, journal = {Experimental cell research}, volume = {419}, number = {2}, pages = {113317}, doi = {10.1016/j.yexcr.2022.113317}, pmid = {36028058}, issn = {1090-2422}, mesh = {Computer Simulation ; Humans ; *Models, Biological ; *Neoplasms ; Tumor Microenvironment ; }, abstract = {Computational models can shape our understanding of cell and tissue remodelling, from cell spreading, to active force generation, adhesion, and growth. In this mini-review, we discuss recent progress in modelling of chemo-mechanical cell behaviour and the evolution of multicellular systems. In particular, we highlight recent advances in (i) free-energy based single cell models that can provide new fundamental insight into cell spreading, cancer cell invasion, stem cell differentiation, and remodelling in disease, and (ii) mechanical agent-based models to simulate large numbers of discrete interacting cells in proliferative tumours. We describe how new biological understanding has emerged from such theoretical models, and the trade-offs and constraints associated with current approaches. Ultimately, we aim to make a case for why theory should be integrated with an experimental workflow to optimise new in-vitro studies, to predict feedback between cells and their microenvironment, and to deepen understanding of active cell behaviour.}, } @article {pmid36011312, year = {2022}, author = {Le, NG and van Ulsen, P and van Spanning, R and Brouwer, A and van Straalen, NM and Roelofs, D}, title = {A Functional Carbohydrate Degrading Enzyme Potentially Acquired by Horizontal Gene Transfer in the Genome of the Soil Invertebrate Folsomia candida.}, journal = {Genes}, volume = {13}, number = {8}, pages = {}, pmid = {36011312}, issn = {2073-4425}, mesh = {Animals ; *Arthropods/genetics ; Bacteria/genetics ; Carbohydrates ; Escherichia coli/genetics ; Eukaryota ; *Gene Transfer, Horizontal ; Insecta ; Protein Sorting Signals/genetics ; Soil ; }, abstract = {Horizontal gene transfer (HGT) is defined as the acquisition by an organism of hereditary material from a phylogenetically unrelated organism. This process is mostly observed among bacteria and archaea, and considered less likely between microbes and multicellular eukaryotes. However, recent studies provide compelling evidence of the evolutionary importance of HGT in eukaryotes, driving functional innovation. Here, we study an HGT event in Folsomia candida (Collembola, Hexapoda) of a carbohydrate-active enzyme homologous to glycosyl hydrase group 43 (GH43). The gene encodes an N-terminal signal peptide, targeting the product for excretion, which suggests that it contributes to the diversity of digestive capacities of the detritivore host. The predicted α-L-arabinofuranosidase shows high similarity to genes in two other Collembola, an insect and a tardigrade. The gene was cloned and expressed in Escherichia coli using a cell-free protein expression system. The expressed protein showed activity against p-nitrophenyl-α-L-arabinofuranoside. Our work provides evidence for functional activity of an HGT gene in a soil-living detritivore, most likely from a bacterial donor, with genuine eukaryotic properties, such as a signal peptide. Co-evolution of metazoan GH43 genes with the Panarthropoda phylogeny suggests the HGT event took place early in the evolution of this ecdysozoan lineage.}, } @article {pmid36002568, year = {2022}, author = {Ocaña-Pallarès, E and Williams, TA and López-Escardó, D and Arroyo, AS and Pathmanathan, JS and Bapteste, E and Tikhonenkov, DV and Keeling, PJ and Szöllősi, GJ and Ruiz-Trillo, I}, title = {Divergent genomic trajectories predate the origin of animals and fungi.}, journal = {Nature}, volume = {609}, number = {7928}, pages = {747-753}, pmid = {36002568}, issn = {1476-4687}, support = {616960/ERC_/European Research Council/International ; 714774/ERC_/European Research Council/International ; 615274/ERC_/European Research Council/International ; }, mesh = {Animals ; *Evolution, Molecular ; *Fungi/genetics ; Gene Transfer, Horizontal ; Genes ; *Genome/genetics ; Genome, Fungal/genetics ; *Genomics ; Metabolism/genetics ; *Phylogeny ; }, abstract = {Animals and fungi have radically distinct morphologies, yet both evolved within the same eukaryotic supergroup: Opisthokonta[1,2]. Here we reconstructed the trajectory of genetic changes that accompanied the origin of Metazoa and Fungi since the divergence of Opisthokonta with a dataset that includes four novel genomes from crucial positions in the Opisthokonta phylogeny. We show that animals arose only after the accumulation of genes functionally important for their multicellularity, a tendency that began in the pre-metazoan ancestors and later accelerated in the metazoan root. By contrast, the pre-fungal ancestors experienced net losses of most functional categories, including those gained in the path to Metazoa. On a broad-scale functional level, fungal genomes contain a higher proportion of metabolic genes and diverged less from the last common ancestor of Opisthokonta than did the gene repertoires of Metazoa. Metazoa and Fungi also show differences regarding gene gain mechanisms. Gene fusions are more prevalent in Metazoa, whereas a larger fraction of gene gains were detected as horizontal gene transfers in Fungi and protists, in agreement with the long-standing idea that transfers would be less relevant in Metazoa due to germline isolation[3-5]. Together, our results indicate that animals and fungi evolved under two contrasting trajectories of genetic change that predated the origin of both groups. The gradual establishment of two clearly differentiated genomic contexts thus set the stage for the emergence of Metazoa and Fungi.}, } @article {pmid36002411, year = {2022}, author = {Shi, B and Huang, X and Fu, X and Wang, B}, title = {[Advances in the plant multicellular network analysis].}, journal = {Sheng wu gong cheng xue bao = Chinese journal of biotechnology}, volume = {38}, number = {8}, pages = {2798-2810}, doi = {10.13345/j.cjb.220127}, pmid = {36002411}, issn = {1872-2075}, mesh = {*Plants ; }, abstract = {Multicellular network analysis is a method for topological properties analysis of cells. The functions of organs are determined by their inner cells. The arrangement of cells within organs endows higher-order functionality through a structure-function relationship, though the organizational properties of these multicellular configurations remain poorly understood. Multicellular network analysis with multicellular models established by 3D scanning of plants, will further discover the plant development mechanism, and provide clues for synthesizing plant multicellular systems. In this paper, we review the development of multicellular models, summarize the process of multicellular network analysis, and describe the development and application of multicellular network analysis in plants. In addition, this review also provides perspective on future development of plant multicellular network analysis.}, } @article {pmid35999597, year = {2022}, author = {Gahan, JM and Leclère, L and Hernandez-Valladares, M and Rentzsch, F}, title = {A developmental role for the chromatin-regulating CoREST complex in the cnidarian Nematostella vectensis.}, journal = {BMC biology}, volume = {20}, number = {1}, pages = {184}, pmid = {35999597}, issn = {1741-7007}, mesh = {Animals ; Cell Differentiation ; *Chromatin ; Histone Demethylases/genetics ; Mammals/genetics ; Phylogeny ; *Sea Anemones/metabolism ; }, abstract = {BACKGROUND: Chromatin-modifying proteins are key players in the regulation of development and cell differentiation in animals. Most chromatin modifiers, however, predate the evolution of animal multicellularity, and how they gained new functions and became integrated into the regulatory networks underlying development is unclear. One way this may occur is the evolution of new scaffolding proteins that integrate multiple chromatin regulators into larger complexes that facilitate coordinated deposition or removal of different chromatin modifications. We test this hypothesis by analyzing the evolution of the CoREST-Lsd1-HDAC complex.

RESULTS: Using phylogenetic analyses, we show that a bona fide CoREST homolog is found only in choanoflagellates and animals. We then use the sea anemone Nematostella vectensis as a model for early branching metazoans and identify a conserved CoREST complex by immunoprecipitation and mass spectrometry of an endogenously tagged Lsd1 allele. In addition to CoREST, Lsd1 and HDAC1/2 this complex contains homologs of HMG20A/B and PHF21A, two subunits that have previously only been identified in mammalian CoREST complexes. NvCoREST expression overlaps fully with that of NvLsd1 throughout development, with higher levels in differentiated neural cells. NvCoREST mutants, generated using CRISPR-Cas9, fail to develop beyond the primary polyp stage, thereby revealing essential roles during development and for the differentiation of cnidocytes that phenocopy NvLsd1 mutants. We also show that this requirement is cell autonomous using a cell-type-specific rescue approach.

CONCLUSIONS: The identification of a Nematostella CoREST-Lsd1-HDAC1/2 complex, its similarity in composition with the vertebrate complex, and the near-identical expression patterns and mutant phenotypes of NvCoREST and NvLsd1 suggest that the complex was present before the last common cnidarian-bilaterian ancestor and thus represents an ancient component of the animal developmental toolkit.}, } @article {pmid35995772, year = {2022}, author = {Nyongesa, S and Weber, PM and Bernet, È and Pulido, F and Nieves, C and Nieckarz, M and Delaby, M and Viehboeck, T and Krause, N and Rivera-Millot, A and Nakamura, A and Vischer, NOE and vanNieuwenhze, M and Brun, YV and Cava, F and Bulgheresi, S and Veyrier, FJ}, title = {Evolution of longitudinal division in multicellular bacteria of the Neisseriaceae family.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {4853}, pmid = {35995772}, issn = {2041-1723}, mesh = {Animals ; Bacterial Proteins/genetics/metabolism ; Biological Evolution ; *Cell Division ; Cell Wall/metabolism ; Mammals/microbiology ; *Neisseriaceae/cytology ; Peptidoglycan/metabolism ; }, abstract = {Rod-shaped bacteria typically elongate and divide by transverse fission. However, several bacterial species can form rod-shaped cells that divide longitudinally. Here, we study the evolution of cell shape and division mode within the family Neisseriaceae, which includes Gram-negative coccoid and rod-shaped species. In particular, bacteria of the genera Alysiella, Simonsiella and Conchiformibius, which can be found in the oral cavity of mammals, are multicellular and divide longitudinally. We use comparative genomics and ultrastructural microscopy to infer that longitudinal division within Neisseriaceae evolved from a rod-shaped ancestor. In multicellular longitudinally-dividing species, neighbouring cells within multicellular filaments are attached by their lateral peptidoglycan. In these bacteria, peptidoglycan insertion does not appear concentric, i.e. from the cell periphery to its centre, but as a medial sheet guillotining each cell. Finally, we identify genes and alleles associated with multicellularity and longitudinal division, including the acquisition of amidase-encoding gene amiC2, and amino acid changes in proteins including MreB and FtsA. Introduction of amiC2 and allelic substitution of mreB in a rod-shaped species that divides by transverse fission results in shorter cells with longer septa. Our work sheds light on the evolution of multicellularity and longitudinal division in bacteria, and suggests that members of the Neisseriaceae family may be good models to study these processes due to their morphological plasticity and genetic tractability.}, } @article {pmid35972622, year = {2022}, author = {Jacques, F and Baratchart, E and Pienta, KJ and Hammarlund, EU}, title = {Origin and evolution of animal multicellularity in the light of phylogenomics and cancer genetics.}, journal = {Medical oncology (Northwood, London, England)}, volume = {39}, number = {11}, pages = {160}, pmid = {35972622}, issn = {1559-131X}, support = {CA163124/CA/NCI NIH HHS/United States ; 949538/ERC_/European Research Council/International ; CA143055/CA/NCI NIH HHS/United States ; U54CA143803/CA/NCI NIH HHS/United States ; CA093900/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; Cell Communication ; Cell Differentiation/genetics ; Eukaryota/genetics ; *Neoplasms/genetics ; Phylogeny ; }, abstract = {The rise of animals represents a major but enigmatic event in the evolutionary history of life. In recent years, numerous studies have aimed at understanding the genetic basis of this transition. However, genome comparisons of diverse animal and protist lineages suggest that the appearance of gene families that were previously considered animal specific indeed preceded animals. Animals' unicellular relatives, such as choanoflagellates, ichthyosporeans, and filastereans, demonstrate complex life cycles including transient multicellularity as well as genetic toolkits for temporal cell differentiation, cell-to-cell communication, apoptosis, and cell adhesion. This has warranted further exploration of the genetic basis underlying transitions in cellular organization. An alternative model for the study of transitions in cellular organization is tumors, which exploit physiological programs that characterize both unicellularity and multicellularity. Tumor cells, for example, switch adhesion on and off, up- or downregulate specific cell differentiation states, downregulate apoptosis, and allow cell migration within tissues. Here, we use insights from both the fields of phylogenomics and tumor biology to review the evolutionary history of the regulatory systems of multicellularity and discuss their overlap. We claim that while evolutionary biology has contributed to an increased understanding of cancer, broad investigations into tissue-normal and transformed-can also contribute the framework for exploring animal evolution.}, } @article {pmid35970862, year = {2022}, author = {Smith, TJ and Donoghue, PCJ}, title = {Evolution of fungal phenotypic disparity.}, journal = {Nature ecology & evolution}, volume = {6}, number = {10}, pages = {1489-1500}, pmid = {35970862}, issn = {2397-334X}, support = {BB/T012773/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/N000919/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; *Biological Evolution ; *Fungi/genetics ; Phenotype ; Plants ; }, abstract = {Organismal-grade multicellularity has been achieved only in animals, plants and fungi. All three kingdoms manifest phenotypically disparate body plans but their evolution has only been considered in detail for animals. Here we tested the general relevance of hypotheses on the evolutionary assembly of animal body plans by characterizing the evolution of fungal phenotypic variety (disparity). The distribution of living fungal form is defined by four distinct morphotypes: flagellated; zygomycetous; sac-bearing; and club-bearing. The discontinuity between morphotypes is a consequence of extinction, indicating that a complete record of fungal disparity would present a more homogeneous distribution of form. Fungal disparity expands episodically through time, punctuated by a sharp increase associated with the emergence of multicellular body plans. Simulations show these temporal trends to be non-random and at least partially shaped by hierarchical contingency. These trends are decoupled from changes in gene number, genome size and taxonomic diversity. Only differences in organismal complexity, characterized as the number of traits that constitute an organism, exhibit a meaningful relationship with fungal disparity. Both animals and fungi exhibit episodic increases in disparity through time, resulting in distributions of form made discontinuous by extinction. These congruences suggest a common mode of multicellular body plan evolution.}, } @article {pmid35948712, year = {2022}, author = {Kim, H and Skinner, DJ and Glass, DS and Hamby, AE and Stuart, BAR and Dunkel, J and Riedel-Kruse, IH}, title = {4-bit adhesion logic enables universal multicellular interface patterning.}, journal = {Nature}, volume = {608}, number = {7922}, pages = {324-329}, pmid = {35948712}, issn = {1476-4687}, mesh = {*Algorithms ; *Artificial Cells/cytology ; Biofilms ; *Cell Adhesion ; Humans ; *Logic ; *Synthetic Biology/methods ; }, abstract = {Multicellular systems, from bacterial biofilms to human organs, form interfaces (or boundaries) between different cell collectives to spatially organize versatile functions[1,2]. The evolution of sufficiently descriptive genetic toolkits probably triggered the explosion of complex multicellular life and patterning[3,4]. Synthetic biology aims to engineer multicellular systems for practical applications and to serve as a build-to-understand methodology for natural systems[5-8]. However, our ability to engineer multicellular interface patterns[2,9] is still very limited, as synthetic cell-cell adhesion toolkits and suitable patterning algorithms are underdeveloped[5,7,10-13]. Here we introduce a synthetic cell-cell adhesin logic with swarming bacteria and establish the precise engineering, predictive modelling and algorithmic programming of multicellular interface patterns. We demonstrate interface generation through a swarming adhesion mechanism, quantitative control over interface geometry and adhesion-mediated analogues of developmental organizers and morphogen fields. Using tiling and four-colour-mapping concepts, we identify algorithms for creating universal target patterns. This synthetic 4-bit adhesion logic advances practical applications such as human-readable molecular diagnostics, spatial fluid control on biological surfaces and programmable self-growing materials[5-8,14]. Notably, a minimal set of just four adhesins represents 4 bits of information that suffice to program universal tessellation patterns, implying a low critical threshold for the evolution and engineering of complex multicellular systems[3,5].}, } @article {pmid35901418, year = {2022}, author = {Raguž, L and Peng, CC and Rutaganira, FUN and Krüger, T and Stanišić, A and Jautzus, T and Kries, H and Kniemeyer, O and Brakhage, AA and King, N and Beemelmanns, C}, title = {Total Synthesis and Functional Evaluation of IORs, Sulfonolipid-based Inhibitors of Cell Differentiation in Salpingoeca rosetta.}, journal = {Angewandte Chemie (International ed. in English)}, volume = {61}, number = {41}, pages = {e202209105}, pmid = {35901418}, issn = {1521-3773}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Cell Differentiation ; *Choanoflagellata ; Lipids ; Proteomics ; Sulfonic Acids ; Zinc ; }, abstract = {The choanoflagellate Salpingoeca rosetta is an important model system to study the evolution of multicellularity. In this study we developed a new, modular, and scalable synthesis of sulfonolipid IOR-1A (six steps, 27 % overall yield), which acts as bacterial inhibitor of rosette formation in S. rosetta. The synthesis features a decarboxylative cross-coupling reaction of a sulfonic acid-containing tartaric acid derivative with alkyl zinc reagents. Synthesis of 15 modified IOR-1A derivatives, including fluorescent and photoaffinity-based probes, allowed quantification of IOR-1A, localization studies within S. rosetta cells, and evaluation of structure-activity relations. In a proof of concept study, an inhibitory bifunctional probe was employed in proteomic profiling studies, which allowed to deduce binding partners in bacteria and S. rosetta. These results showcase the power of synthetic chemistry to decipher the biochemical basis of cell differentiation processes within S. rosetta.}, } @article {pmid35894230, year = {2022}, author = {Le Gloanec, C and Collet, L and Silveira, SR and Wang, B and Routier-Kierzkowska, AL and Kierzkowski, D}, title = {Cell type-specific dynamics underlie cellular growth variability in plants.}, journal = {Development (Cambridge, England)}, volume = {149}, number = {14}, pages = {}, doi = {10.1242/dev.200783}, pmid = {35894230}, issn = {1477-9129}, mesh = {*Arabidopsis ; *Arabidopsis Proteins/genetics ; Cell Differentiation/genetics ; Cell Proliferation ; Plant Leaves ; Plant Stomata ; }, abstract = {Coordination of growth, patterning and differentiation is required for shaping organs in multicellular organisms. In plants, cell growth is controlled by positional information, yet the behavior of individual cells is often highly heterogeneous. The origin of this variability is still unclear. Using time-lapse imaging, we determined the source and relevance of cellular growth variability in developing organs of Arabidopsis thaliana. We show that growth is more heterogeneous in the leaf blade than in the midrib and petiole, correlating with higher local differences in growth rates between neighboring cells in the blade. This local growth variability coincides with developing stomata. Stomatal lineages follow a specific, time-dependent growth program that is different from that of their surroundings. Quantification of cellular dynamics in the leaves of a mutant lacking stomata, as well as analysis of floral organs, supports the idea that growth variability is mainly driven by stomata differentiation. Thus, the cell-autonomous behavior of specialized cells is the main source of local growth variability in otherwise homogeneously growing tissue. Those growth differences are buffered by the immediate neighbors of stomata and trichomes to achieve robust organ shapes.}, } @article {pmid35893123, year = {2022}, author = {Dijkwel, Y and Tremethick, DJ}, title = {The Role of the Histone Variant H2A.Z in Metazoan Development.}, journal = {Journal of developmental biology}, volume = {10}, number = {3}, pages = {}, pmid = {35893123}, issn = {2221-3759}, abstract = {During the emergence and radiation of complex multicellular eukaryotes from unicellular ancestors, transcriptional systems evolved by becoming more complex to provide the basis for this morphological diversity. The way eukaryotic genomes are packaged into a highly complex structure, known as chromatin, underpins this evolution of transcriptional regulation. Chromatin structure is controlled by a variety of different epigenetic mechanisms, including the major mechanism for altering the biochemical makeup of the nucleosome by replacing core histones with their variant forms. The histone H2A variant H2A.Z is particularly important in early metazoan development because, without it, embryos cease to develop and die. However, H2A.Z is also required for many differentiation steps beyond the stage that H2A.Z-knockout embryos die. H2A.Z can facilitate the activation and repression of genes that are important for pluripotency and differentiation, and acts through a variety of different molecular mechanisms that depend upon its modification status, its interaction with histone and nonhistone partners, and where it is deposited within the genome. In this review, we discuss the current knowledge about the different mechanisms by which H2A.Z regulates chromatin function at various developmental stages and the chromatin remodeling complexes that determine when and where H2A.Z is deposited.}, } @article {pmid35879542, year = {2022}, author = {Ní Leathlobhair, M and Lenski, RE}, title = {Population genetics of clonally transmissible cancers.}, journal = {Nature ecology & evolution}, volume = {6}, number = {8}, pages = {1077-1089}, pmid = {35879542}, issn = {2397-334X}, mesh = {Animals ; Biological Evolution ; *Genetics, Population ; Genome ; *Neoplasms/genetics ; Population Dynamics ; }, abstract = {Populations of cancer cells are subject to the same core evolutionary processes as asexually reproducing, unicellular organisms. Transmissible cancers are particularly striking examples of these processes. These unusual cancers are clonal lineages that can spread through populations via physical transfer of living cancer cells from one host individual to another, and they have achieved long-term success in the colonization of at least eight different host species. Population genetic theory provides a useful framework for understanding the shift from a multicellular sexual animal into a unicellular asexual clone and its long-term effects on the genomes of these cancers. In this Review, we consider recent findings from transmissible cancer research with the goals of developing an evolutionarily informed perspective on transmissible cancers, examining possible implications for their long-term fate and identifying areas for future research on these exceptional lineages.}, } @article {pmid35862435, year = {2022}, author = {Howe, J and Rink, JC and Wang, B and Griffin, AS}, title = {Multicellularity in animals: The potential for within-organism conflict.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {119}, number = {32}, pages = {e2120457119}, pmid = {35862435}, issn = {1091-6490}, mesh = {Animals ; *Biological Evolution ; *Cell Lineage ; Clone Cells ; Developmental Biology ; *Insecta/growth & development ; Reproduction ; }, abstract = {Metazoans function as individual organisms but also as "colonies" of cells whose single-celled ancestors lived and reproduced independently. Insights from evolutionary biology about multicellular group formation help us understand the behavior of cells: why they cooperate, and why cooperation sometimes breaks down. Current explanations for multicellularity focus on two aspects of development which promote cooperation and limit conflict among cells: a single-cell bottleneck, which creates organisms composed of clones, and a separation of somatic and germ cell lineages, which reduces the selective advantage of cheating. However, many obligately multicellular organisms thrive with neither, creating the potential for within-organism conflict. Here, we argue that the prevalence of such organisms throughout the Metazoa requires us to refine our preconceptions of conflict-free multicellularity. Evolutionary theory must incorporate developmental mechanisms across a broad range of organisms-such as unusual reproductive strategies, totipotency, and cell competition-while developmental biology must incorporate evolutionary principles. To facilitate this cross-disciplinary approach, we provide a conceptual overview from evolutionary biology for developmental biologists, using analogous examples in the well-studied social insects.}, } @article {pmid35858311, year = {2022}, author = {Belcher, LJ and Madgwick, PG and Kuwana, S and Stewart, B and Thompson, CRL and Wolf, JB}, title = {Developmental constraints enforce altruism and avert the tragedy of the commons in a social microbe.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {119}, number = {29}, pages = {e2111233119}, pmid = {35858311}, issn = {1091-6490}, mesh = {*Altruism ; Biological Evolution ; Cooperative Behavior ; *Dictyostelium ; Humans ; Motivation ; }, abstract = {Organisms often cooperate through the production of freely available public goods. This can greatly benefit the group but is vulnerable to the "tragedy of the commons" if individuals lack the motivation to make the necessary investment into public goods production. Relatedness to groupmates can motivate individual investment because group success ultimately benefits their genes' own self-interests. However, systems often lack mechanisms that can reliably ensure that relatedness is high enough to promote cooperation. Consequently, groups face a persistent threat from the tragedy unless they have a mechanism to enforce investment when relatedness fails to provide adequate motivation. To understand the real threat posed by the tragedy and whether groups can avert its impact, we determine how the social amoeba Dictyostelium discoideum responds as relatedness decreases to levels that should induce the tragedy. We find that, while investment in public goods declines as overall within-group relatedness declines, groups avert the expected catastrophic collapse of the commons by continuing to invest, even when relatedness should be too low to incentivize any contribution. We show that this is due to a developmental buffering system that generates enforcement because insufficient cooperation perturbs the balance of a negative feedback system controlling multicellular development. This developmental constraint enforces investment under the conditions expected to be most tragic, allowing groups to avert a collapse in cooperation. These results help explain how mechanisms that suppress selfishness and enforce cooperation can arise inadvertently as a by-product of constraints imposed by selection on different traits.}, } @article {pmid35852417, year = {2022}, author = {Chakravarty, AK and McGrail, DJ and Lozanoski, TM and Dunn, BS and Shih, DJH and Cirillo, KM and Cetinkaya, SH and Zheng, WJ and Mills, GB and Yi, SS and Jarosz, DF and Sahni, N}, title = {Biomolecular Condensation: A New Phase in Cancer Research.}, journal = {Cancer discovery}, volume = {12}, number = {9}, pages = {2031-2043}, pmid = {35852417}, issn = {2159-8290}, support = {K99 GM128180/GM/NIGMS NIH HHS/United States ; R35 GM137836/GM/NIGMS NIH HHS/United States ; K99 CA240689/CA/NCI NIH HHS/United States ; DRG2221-15/HHMI/Howard Hughes Medical Institute/United States ; U01 CA217842/CA/NCI NIH HHS/United States ; R35 GM133658/GM/NIGMS NIH HHS/United States ; DP2 GM119140/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Neoplasms/metabolism ; *Organelles/metabolism ; Research ; }, abstract = {UNLABELLED: Multicellularity was a watershed development in evolution. However, it also meant that individual cells could escape regulatory mechanisms that restrict proliferation at a severe cost to the organism: cancer. From the standpoint of cellular organization, evolutionary complexity scales to organize different molecules within the intracellular milieu. The recent realization that many biomolecules can "phase-separate" into membraneless organelles, reorganizing cellular biochemistry in space and time, has led to an explosion of research activity in this area. In this review, we explore mechanistic connections between phase separation and cancer-associated processes and emerging examples of how these become deranged in malignancy.

SIGNIFICANCE: One of the fundamental functions of phase separation is to rapidly and dynamically respond to environmental perturbations. Importantly, these changes often lead to alterations in cancer-relevant pathways and processes. This review covers recent advances in the field, including emerging principles and mechanisms of phase separation in cancer.}, } @article {pmid35849348, year = {2022}, author = {Wu, TY and Hoh, KL and Boonyaves, K and Krishnamoorthi, S and Urano, D}, title = {Diversification of heat shock transcription factors expanded thermal stress responses during early plant evolution.}, journal = {The Plant cell}, volume = {34}, number = {10}, pages = {3557-3576}, pmid = {35849348}, issn = {1532-298X}, mesh = {*Arabidopsis/metabolism ; Gene Expression Regulation, Plant/genetics ; Gene Regulatory Networks ; Heat Shock Transcription Factors/metabolism ; Heat-Shock Response/genetics ; *Marchantia/genetics/metabolism ; Plant Proteins/genetics/metabolism ; }, abstract = {The copy numbers of many plant transcription factor (TF) genes substantially increased during terrestrialization. This allowed TFs to acquire new specificities and thus create gene regulatory networks (GRNs) with new biological functions to help plants adapt to terrestrial environments. Through characterizing heat shock factor (HSF) genes MpHSFA1 and MpHSFB1 in the liverwort Marchantia polymorpha, we explored how heat-responsive GRNs widened their functions in M. polymorpha and Arabidopsis thaliana. An interspecies comparison of heat-induced transcriptomes and the evolutionary rates of HSFs demonstrated the emergence and subsequent rapid evolution of HSFB prior to terrestrialization. Transcriptome and metabolome analyses of M. polymorpha HSF-null mutants revealed that MpHSFA1 controls canonical heat responses such as thermotolerance and metabolic changes. MpHSFB1 also plays essential roles in heat responses, as well as regulating developmental processes including meristem branching and antheridiophore formation. Analysis of cis-regulatory elements revealed development- and stress-related TFs that function directly or indirectly downstream of HSFB. Male gametophytes of M. polymorpha showed higher levels of thermotolerance than female gametophytes, which could be explained by different expression levels of MpHSFA1U and MpHSFA1V on sex chromosome. We propose that the diversification of HSFs is linked to the expansion of HS responses, which enabled coordinated multicellular reactions in land plants.}, } @article {pmid35841659, year = {2022}, author = {Gabaldón, T and Völcker, E and Torruella, G}, title = {On the Biology, Diversity and Evolution of Nucleariid Amoebae (Amorphea, Obazoa, Opisthokonta[1].}, journal = {Protist}, volume = {173}, number = {4}, pages = {125895}, doi = {10.1016/j.protis.2022.125895}, pmid = {35841659}, issn = {1618-0941}, mesh = {*Amoeba ; Animals ; Biology ; Eukaryota ; Fungi ; Phylogeny ; }, abstract = {Nucleariids are a small group of free-living heterotrophic amoebae. Although these organisms present a variety of cell sizes and cell coverings, they are mostly spherical cells with radiating filopodia, sometimes with several nuclei. Nuclearia, the genus that gives the name to the group, contains species that are opportunistic consumers of detritus, bacteria, and algae. The beautiful Pompholyxophrys is covered with endogenous siliceous pearls. Lithocolla covers itself with sand particles, or otherwise diatom frustules. The tiny Parvularia exclusively feeds on bacteria, and Fonticula is adapted to solid substrates and presents aggregative multicellular stages. Nucleariids belong to the Opisthokonta, which comprise animals, fungi, and their protist relatives, and form the earliest branch in the holomycotan clade (fungi and closest relatives). Hence, they are key for understanding the origin and diversification of Opisthokonta, an eukaryotic supergroup that contains organisms with different feeding modes, life-styles, and cell organizations. In this review, the reader will find an introduction to nucleariids, from their discovery in the 19th century until the most recent studies. It summarizes available information on their morphology, life history, cell organisation, ecology, diversity, systematics and evolution.}, } @article {pmid35838349, year = {2022}, author = {Meléndez García, R and Haccard, O and Chesneau, A and Narassimprakash, H and Roger, J and Perron, M and Marheineke, K and Bronchain, O}, title = {A non-transcriptional function of Yap regulates the DNA replication program in Xenopus laevis.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {35838349}, issn = {2050-084X}, mesh = {Animals ; DNA Replication ; DNA Replication Timing ; *Replication Origin ; S Phase/genetics ; *Telomere-Binding Proteins/genetics ; Xenopus laevis/genetics/metabolism ; }, abstract = {In multicellular eukaryotic organisms, the initiation of DNA replication occurs asynchronously throughout S-phase according to a regulated replication timing program. Here, using Xenopus egg extracts, we showed that Yap (Yes-associated protein 1), a downstream effector of the Hippo signalling pathway, is required for the control of DNA replication dynamics. We found that Yap is recruited to chromatin at the start of DNA replication and identified Rif1, a major regulator of the DNA replication timing program, as a novel Yap binding protein. Furthermore, we show that either Yap or Rif1 depletion accelerates DNA replication dynamics by increasing the number of activated replication origins. In Xenopus embryos, using a Trim-Away approach during cleavage stages devoid of transcription, we found that either Yap or Rif1 depletion triggers an acceleration of cell divisions, suggesting a shorter S-phase by alterations of the replication program. Finally, our data show that Rif1 knockdown leads to defects in the partitioning of early versus late replication foci in retinal stem cells, as we previously showed for Yap. Altogether, our findings unveil a non-transcriptional role for Yap in regulating replication dynamics. We propose that Yap and Rif1 function as brakes to control the DNA replication program in early embryos and post-embryonic stem cells.}, } @article {pmid35804300, year = {2022}, author = {Angaroni, F and Guidi, A and Ascolani, G and d'Onofrio, A and Antoniotti, M and Graudenzi, A}, title = {J-SPACE: a Julia package for the simulation of spatial models of cancer evolution and of sequencing experiments.}, journal = {BMC bioinformatics}, volume = {23}, number = {1}, pages = {269}, pmid = {35804300}, issn = {1471-2105}, support = {22790/CRUK_/Cancer Research UK/United Kingdom ; 22790/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Computer Simulation ; High-Throughput Nucleotide Sequencing/methods ; Humans ; *Neoplasms/genetics/pathology ; Phylogeny ; *Software ; }, abstract = {BACKGROUND: The combined effects of biological variability and measurement-related errors on cancer sequencing data remain largely unexplored. However, the spatio-temporal simulation of multi-cellular systems provides a powerful instrument to address this issue. In particular, efficient algorithmic frameworks are needed to overcome the harsh trade-off between scalability and expressivity, so to allow one to simulate both realistic cancer evolution scenarios and the related sequencing experiments, which can then be used to benchmark downstream bioinformatics methods.

RESULT: We introduce a Julia package for SPAtial Cancer Evolution (J-SPACE), which allows one to model and simulate a broad set of experimental scenarios, phenomenological rules and sequencing settings.Specifically, J-SPACE simulates the spatial dynamics of cells as a continuous-time multi-type birth-death stochastic process on a arbitrary graph, employing different rules of interaction and an optimised Gillespie algorithm. The evolutionary dynamics of genomic alterations (single-nucleotide variants and indels) is simulated either under the Infinite Sites Assumption or several different substitution models, including one based on mutational signatures. After mimicking the spatial sampling of tumour cells, J-SPACE returns the related phylogenetic model, and allows one to generate synthetic reads from several Next-Generation Sequencing (NGS) platforms, via the ART read simulator. The results are finally returned in standard FASTA, FASTQ, SAM, ALN and Newick file formats.

CONCLUSION: J-SPACE is designed to efficiently simulate the heterogeneous behaviour of a large number of cancer cells and produces a rich set of outputs. Our framework is useful to investigate the emergent spatial dynamics of cancer subpopulations, as well as to assess the impact of incomplete sampling and of experiment-specific errors. Importantly, the output of J-SPACE is designed to allow the performance assessment of downstream bioinformatics pipelines processing NGS data. J-SPACE is freely available at: https://github.com/BIMIB-DISCo/J-Space.jl .}, } @article {pmid35792830, year = {2022}, author = {Fukai, E and Yoshikawa, M and Shah, N and Sandal, N and Miyao, A and Ono, S and Hirakawa, H and Akyol, TY and Umehara, Y and Nonomura, KI and Stougaard, J and Hirochika, H and Hayashi, M and Sato, S and Andersen, SU and Okazaki, K}, title = {Widespread and transgenerational retrotransposon activation in inter- and intraspecies recombinant inbred populations of Lotus japonicus.}, journal = {The Plant journal : for cell and molecular biology}, volume = {111}, number = {5}, pages = {1397-1410}, doi = {10.1111/tpj.15896}, pmid = {35792830}, issn = {1365-313X}, mesh = {Evolution, Molecular ; Genome, Plant/genetics ; Hybridization, Genetic ; *Lotus/genetics ; Plants/genetics ; *Retroelements/genetics ; Terminal Repeat Sequences/genetics ; }, abstract = {Transposable elements (TEs) constitute a large proportion of genomes of multicellular eukaryotes, including flowering plants. TEs are normally maintained in a silenced state and their transpositions rarely occur. Hybridization between distant species has been regarded as a 'shock' that stimulates genome reorganization, including TE mobilization. However, whether crosses between genetically close parents that result in viable and fertile offspring can induce TE transpositions has remained unclear. Here, we investigated the activation of long terminal repeat (LTR) retrotransposons in three Lotus japonicus recombinant inbred line (RIL) populations. We found that at least six LTR retrotransposon families were activated and transposed in 78% of the RILs investigated. LORE1a, one of the transposed LTR retrotransposons, showed transgenerational epigenetic activation, indicating the long-term effects of epigenetic instability induced by hybridization. Our study highlights TE activation as an unexpectedly common event in plant reproduction.}, } @article {pmid35790840, year = {2022}, author = {Beljan, S and Dominko, K and Talajić, A and Hloušek-Kasun, A and Škrobot Vidaček, N and Herak Bosnar, M and Vlahoviček, K and Ćetković, H}, title = {Structure and function of cancer-related developmentally regulated GTP-binding protein 1 (DRG1) is conserved between sponges and humans.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {11379}, pmid = {35790840}, issn = {2045-2322}, mesh = {Animals ; GTP-Binding Proteins ; Genomics ; Humans ; *Neoplasms/genetics ; *Oncogenes ; RNA ; Transcription Factors ; }, abstract = {Cancer is a disease caused by errors within the multicellular system and it represents a major health issue in multicellular organisms. Although cancer research has advanced substantially, new approaches focusing on fundamental aspects of cancer origin and mechanisms of spreading are necessary. Comparative genomic studies have shown that most genes linked to human cancer emerged during the early evolution of Metazoa. Thus, basal animals without true tissues and organs, such as sponges (Porifera), might be an innovative model system for understanding the molecular mechanisms of proteins involved in cancer biology. One of these proteins is developmentally regulated GTP-binding protein 1 (DRG1), a GTPase stabilized by interaction with DRG family regulatory protein 1 (DFRP1). This study reveals a high evolutionary conservation of DRG1 gene/protein in metazoans. Our biochemical analysis and structural predictions show that both recombinant sponge and human DRG1 are predominantly monomers that form complexes with DFRP1 and bind non-specifically to RNA and DNA. We demonstrate the conservation of sponge and human DRG1 biological features, including intracellular localization and DRG1:DFRP1 binding, function of DRG1 in α-tubulin dynamics, and its role in cancer biology demonstrated by increased proliferation, migration and colonization in human cancer cells. These results suggest that the ancestor of all Metazoa already possessed DRG1 that is structurally and functionally similar to the human DRG1, even before the development of real tissues or tumors, indicating an important function of DRG1 in fundamental cellular pathways.}, } @article {pmid35778439, year = {2022}, author = {Belpaire, TER and Pešek, J and Lories, B and Verstrepen, KJ and Steenackers, HP and Ramon, H and Smeets, B}, title = {Permissive aggregative group formation favors coexistence between cooperators and defectors in yeast.}, journal = {The ISME journal}, volume = {16}, number = {10}, pages = {2305-2312}, pmid = {35778439}, issn = {1751-7370}, mesh = {Biological Evolution ; Flocculation ; Mannose-Binding Lectins/chemistry/genetics/metabolism ; *Saccharomyces cerevisiae/genetics/metabolism ; *Saccharomyces cerevisiae Proteins/chemistry/genetics/metabolism ; }, abstract = {In Saccharomyces cerevisiae, the FLO1 gene encodes flocculins that lead to formation of multicellular flocs, that offer protection to the constituent cells. Flo1p was found to preferentially bind to fellow cooperators compared to defectors lacking FLO1 expression, enriching cooperators within the flocs. Given this dual function in cooperation and kin recognition, FLO1 has been termed a "green beard gene". Because of the heterophilic nature of the Flo1p bond however, we hypothesize that kin recognition is permissive and depends on the relative stability of the FLO1[+]/flo1[-] versus FLO1[+]/FLO1[+] detachment force F. We combine single-cell measurements of adhesion, individual cell-based simulations of cluster formation, and in vitro flocculation to study the impact of relative bond stability on the evolutionary stability of cooperation. We identify a trade-off between both aspects of the green beard mechanism, with reduced relative bond stability leading to increased kin recognition at the expense of cooperative benefits. We show that the fitness of FLO1 cooperators decreases as their frequency in the population increases, arising from the observed permissive character (F+- = 0.5 F++) of the Flo1p bond. Considering the costs associated with FLO1 expression, this asymmetric selection often results in a stable coexistence between cooperators and defectors.}, } @article {pmid35728616, year = {2022}, author = {Cameron-Pack, ME and König, SG and Reyes-Guevara, A and Reyes-Prieto, A and Nedelcu, AM}, title = {A personal cost of cheating can stabilize reproductive altruism during the early evolution of clonal multicellularity.}, journal = {Biology letters}, volume = {18}, number = {6}, pages = {20220059}, pmid = {35728616}, issn = {1744-957X}, mesh = {*Altruism ; Biological Evolution ; Reproduction ; *Volvox/genetics ; }, abstract = {Understanding how cooperation evolved and is maintained remains an important and often controversial topic because cheaters that reap the benefits of cooperation without paying the costs can threaten the evolutionary stability of cooperative traits. Cooperation-and especially reproductive altruism-is particularly relevant to the evolution of multicellularity, as somatic cells give up their reproductive potential in order to contribute to the fitness of the newly emerged multicellular individual. Here, we investigated cheating in a simple multicellular species-the green alga Volvox carteri, in the context of the mechanisms that can stabilize reproductive altruism during the early evolution of clonal multicellularity. We found that the benefits cheater mutants can gain in terms of their own reproduction are pre-empted by a cost in survival due to increased sensitivity to stress. This personal cost of cheating reflects the antagonistic pleiotropic effects that the gene coding for reproductive altruism-regA-has at the cell level. Specifically, the expression of regA in somatic cells results in the suppression of their reproduction potential but also confers them with increased resistance to stress. Since regA evolved from a life-history trade-off gene, we suggest that co-opting trade-off genes into cooperative traits can provide a built-in safety system against cheaters in other clonal multicellular lineages.}, } @article {pmid35726057, year = {2022}, author = {Kaufmann, M and Schaupp, AL and Sun, R and Coscia, F and Dendrou, CA and Cortes, A and Kaur, G and Evans, HG and Mollbrink, A and Navarro, JF and Sonner, JK and Mayer, C and DeLuca, GC and Lundeberg, J and Matthews, PM and Attfield, KE and Friese, MA and Mann, M and Fugger, L}, title = {Identification of early neurodegenerative pathways in progressive multiple sclerosis.}, journal = {Nature neuroscience}, volume = {25}, number = {7}, pages = {944-955}, pmid = {35726057}, issn = {1546-1726}, support = {100308/Z/12/Z/WT_/Wellcome Trust/United Kingdom ; /DH_/Department of Health/United Kingdom ; MC_UU_12010/3/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*Central Nervous System Diseases/complications ; Disease Progression ; Humans ; *Multiple Sclerosis/pathology ; Neurons/metabolism ; Proteomics ; }, abstract = {Progressive multiple sclerosis (MS) is characterized by unrelenting neurodegeneration, which causes cumulative disability and is refractory to current treatments. Drug development to prevent disease progression is an urgent clinical need yet is constrained by an incomplete understanding of its complex pathogenesis. Using spatial transcriptomics and proteomics on fresh-frozen human MS brain tissue, we identified multicellular mechanisms of progressive MS pathogenesis and traced their origin in relation to spatially distributed stages of neurodegeneration. By resolving ligand-receptor interactions in local microenvironments, we discovered defunct trophic and anti-inflammatory intercellular communications within areas of early neuronal decline. Proteins associated with neuronal damage in patient samples showed mechanistic concordance with published in vivo knockdown and central nervous system (CNS) disease models, supporting their causal role and value as potential therapeutic targets in progressive MS. Our findings provide a new framework for drug development strategies, rooted in an understanding of the complex cellular and signaling dynamics in human diseased tissue that facilitate this debilitating disease.}, } @article {pmid35725583, year = {2022}, author = {Mori, G and Delfino, D and Pibiri, P and Rivetti, C and Percudani, R}, title = {Origin and significance of the human DNase repertoire.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {10364}, pmid = {35725583}, issn = {2045-2322}, mesh = {Animals ; DNA/genetics ; Deoxyribonuclease I/genetics ; *Deoxyribonucleases/genetics ; *Evolution, Molecular ; Fishes/genetics ; Gene Duplication ; Humans ; Phylogeny ; Synteny ; Vertebrates/genetics ; }, abstract = {The human genome contains four DNase1 and two DNase2 genes. The origin and functional specialization of this repertoire are not fully understood. Here we use genomics and transcriptomics data to infer the evolutionary history of DNases and investigate their biological significance. Both DNase1 and DNase2 families have expanded in vertebrates since ~ 650 million years ago before the divergence of jawless and jawed vertebrates. DNase1, DNase1L1, and DNase1L3 co-existed in jawless fish, whereas DNase1L2 originated in amniotes by tandem duplication of DNase1. Among the non-human DNases, DNase1L4 and newly identified DNase1L5 derived from early duplications that were lost in terrestrial vertebrates. The ancestral gene of the DNase2 family, DNase2b, has been conserved in synteny with the Uox gene across 700 million years of animal evolution,while DNase2 originated in jawless fish. DNase1L1 acquired a GPI-anchor for plasma membrane attachment in bony fishes, and DNase1L3 acquired a C-terminal basic peptide for the degradation of microparticle DNA in jawed vertebrates. The appearance of DNase1L2, with a distinct low pH optimum and skin localization, is among the amniote adaptations to life on land. The expansion of the DNase repertoire in vertebrates meets the diversified demand for DNA debris removal in complex multicellular organisms.}, } @article {pmid35713948, year = {2022}, author = {Passer, AR and Clancey, SA and Shea, T and David-Palma, M and Averette, AF and Boekhout, T and Porcel, BM and Nowrousian, M and Cuomo, CA and Sun, S and Heitman, J and Coelho, MA}, title = {Obligate sexual reproduction of a homothallic fungus closely related to the Cryptococcus pathogenic species complex.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {35713948}, issn = {2050-084X}, support = {U54 HG003067/HG/NHGRI NIH HHS/United States ; }, mesh = {Biological Evolution ; *Cryptococcus neoformans/genetics ; *Genes, Mating Type, Fungal/genetics ; Humans ; Reproduction ; Saccharomyces cerevisiae/genetics ; }, abstract = {eLife digest. Fungi are enigmatic organisms that flourish in soil, on decaying plants, or during infection of animals or plants. Growing in myriad forms, from single-celled yeast to multicellular molds and mushrooms, fungi have also evolved a variety of strategies to reproduce. Normally, fungi reproduce in one of two ways: either they reproduce asexually, with one individual producing a new individual identical to itself, or they reproduce sexually, with two individuals of different 'mating types' contributing to produce a new individual. However, individuals of some species exhibit 'homothallism' or self-fertility: these individuals can produce reproductive cells that are universally compatible, and therefore can reproduce sexually with themselves or with any other cell in the population. Homothallism has evolved multiple times throughout the fungal kingdom, suggesting it confers advantage when population numbers are low or mates are hard to find. Yet some homothallic fungi been overlooked compared to heterothallic species, whose mating types have been well characterised. Understanding the genetic basis of homothallism and how it evolved in different species can provide insights into pathogenic species that cause fungal disease. With that in mind, Passer, Clancey et al. explored the genetic basis of homothallism in Cryptococcus depauperatus, a close relative of C. neoformans, a species that causes fungal infections in humans. A combination of genetic sequencing techniques and experiments were applied to analyse, compare, and manipulate C. depauperatus' genome to see how this species evolved self-fertility. Passer, Clancey et al. showed that C. depauperatus evolved the ability to reproduce sexually by itself via a unique evolutionary pathway. The result is a form of homothallism never reported in fungi before. C. depauperatus lost some of the genes that control mating in other species of fungi, and acquired genes from the opposing mating types of a heterothallic ancestor to become self-fertile. Passer, Clancey et al. also found that, unlike other Cryptococcus species that switch between asexual and sexual reproduction, C. depauperatus grows only as long, branching filaments called hyphae, a sexual form. The species reproduces sexually with itself throughout its life cycle and is unable to produce a yeast (asexual) form, in contrast to other closely related species. This work offers new insights into how different modes of sexual reproduction have evolved in fungi. It also provides another interesting case of how genome plasticity and evolutionary pressures can produce similar outcomes, homothallism, via different evolutionary paths. Lastly, assembling the complete genome of C. depauperatus will foster comparative studies between pathogenic and non-pathogenic Cryptococcus species.}, } @article {pmid35681485, year = {2022}, author = {Minelli, A and Valero-Gracia, A}, title = {Spatially and Temporally Distributed Complexity-A Refreshed Framework for the Study of GRN Evolution.}, journal = {Cells}, volume = {11}, number = {11}, pages = {}, pmid = {35681485}, issn = {2073-4409}, mesh = {Animals ; *Gene Regulatory Networks ; Genotype ; Phenotype ; }, abstract = {Irrespective of the heuristic value of interpretations of developmental processes in terms of gene regulatory networks (GRNs), larger-angle views often suffer from: (i) an inadequate understanding of the relationship between genotype and phenotype; (ii) a predominantly zoocentric vision; and (iii) overconfidence in a putatively hierarchical organization of animal body plans. Here, we constructively criticize these assumptions. First, developmental biology is pervaded by adultocentrism, but development is not necessarily egg to adult. Second, during development, many unicells undergo transcriptomic profile transitions that are comparable to those recorded in pluricellular organisms; thus, their study should not be neglected from the GRN perspective. Third, the putatively hierarchical nature of the animal body is mirrored in the GRN logic, but in relating genotype to phenotype, independent assessments of the dynamics of the regulatory machinery and the animal's architecture are required, better served by a combinatorial than by a hierarchical approach. The trade-offs between spatial and temporal aspects of regulation, as well as their evolutionary consequences, are also discussed. Multicellularity may derive from a unicell's sequential phenotypes turned into different but coexisting, spatially arranged cell types. In turn, polyphenism may have been a crucial mechanism involved in the origin of complex life cycles.}, } @article {pmid35678467, year = {2022}, author = {Northey, JJ and Weaver, VM}, title = {Mechanosensitive Steroid Hormone Signaling and Cell Fate.}, journal = {Endocrinology}, volume = {163}, number = {8}, pages = {}, pmid = {35678467}, issn = {1945-7170}, support = {R35 CA242447/CA/NCI NIH HHS/United States ; R01 CA192914/CA/NCI NIH HHS/United States ; R01 CA222508/CA/NCI NIH HHS/United States ; }, mesh = {Cell Differentiation ; Hormones/physiology ; Humans ; *Neoplasms/pathology ; *Receptors, Steroid ; Signal Transduction ; Steroids ; }, abstract = {Mechanical forces collaborate across length scales to coordinate cell fate during development and the dynamic homeostasis of adult tissues. Similarly, steroid hormones interact with their nuclear and nonnuclear receptors to regulate diverse physiological processes necessary for the appropriate development and function of complex multicellular tissues. Aberrant steroid hormone action is associated with tumors originating in hormone-sensitive tissues and its disruption forms the basis of several therapeutic interventions. Prolonged perturbations to mechanical forces may further foster tumor initiation and the evolution of aggressive metastatic disease. Recent evidence suggests that steroid hormone and mechanical signaling intersect to direct cell fate during development and tumor progression. Potential mechanosensitive steroid hormone signaling pathways along with their molecular effectors will be discussed in this context.}, } @article {pmid35660859, year = {2022}, author = {Bao, L and Ren, J and Nguyen, M and Slusarczyk, AS and Thole, JM and Martinez, SP and Huang, J and Fujita, T and Running, MP}, title = {The cellular function of ROP GTPase prenylation is important for multicellularity in the moss Physcomitrium patens.}, journal = {Development (Cambridge, England)}, volume = {149}, number = {12}, pages = {}, doi = {10.1242/dev.200279}, pmid = {35660859}, issn = {1477-9129}, mesh = {*Bryopsida/metabolism ; Cell Wall/metabolism ; *GTP Phosphohydrolases/metabolism ; Prenylation ; Signal Transduction ; }, abstract = {A complete picture of how signaling pathways lead to multicellularity is largely unknown. Previously, we generated mutations in a protein prenylation enzyme, GGB, and showed that it is essential for maintaining multicellularity in the moss Physcomitrium patens. Here, we show that ROP GTPases act as downstream factors that are prenylated by GGB and themselves play an important role in the multicellularity of P. patens. We also show that the loss of multicellularity caused by the suppression of GGB or ROP GTPases is due to uncoordinated cell expansion, defects in cell wall integrity and the disturbance of the directional control of cell plate orientation. Expressing prenylatable ROP in the ggb mutant not only rescues multicellularity in protonemata but also results in development of gametophores. Although the prenylation of ROP is important for multicellularity, a higher threshold of active ROP is required for gametophore development. Thus, our results suggest that ROP activation via prenylation by GGB is a key process at both cell and tissue levels, facilitating the developmental transition from one dimension to two dimensions and to three dimensions in P. patens.}, } @article {pmid35659869, year = {2022}, author = {Phillips, JE and Santos, M and Konchwala, M and Xing, C and Pan, D}, title = {Genome editing in the unicellular holozoan Capsaspora owczarzaki suggests a premetazoan role for the Hippo pathway in multicellular morphogenesis.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {35659869}, issn = {2050-084X}, mesh = {Animals ; Eukaryota/genetics ; *Evolution, Molecular ; *Gene Editing ; Hippo Signaling Pathway ; Morphogenesis ; }, abstract = {Animal development is mediated by a surprisingly small set of canonical signaling pathways such as Wnt, Hedgehog, TGF-beta, Notch, and Hippo pathways. Although once thought to be present only in animals, recent genome sequencing has revealed components of these pathways in the closest unicellular relatives of animals. These findings raise questions about the ancestral functions of these developmental pathways and their potential role in the emergence of animal multicellularity. Here, we provide the first functional characterization of any of these developmental pathways in unicellular organisms by developing techniques for genetic manipulation in Capsaspora owczarzaki, a close unicellular relative of animals that displays aggregative multicellularity. We then use these tools to characterize the Capsaspora ortholog of the Hippo signaling nuclear effector YAP/TAZ/Yorkie (coYki), a key regulator of tissue size in animals. In contrast to what might be expected based on studies in animals, we show that coYki is dispensable for cell proliferation but regulates cytoskeletal dynamics and the three-dimensional (3D) shape of multicellular structures. We further demonstrate that the cytoskeletal abnormalities of individual coYki mutant cells underlie the abnormal 3D shape of coYki mutant aggregates. Taken together, these findings implicate an ancestral role for the Hippo pathway in cytoskeletal dynamics and multicellular morphogenesis predating the origin of animal multicellularity, which was co-opted during evolution to regulate cell proliferation.}, } @article {pmid35651757, year = {2022}, author = {Díaz, E and Febres, A and Giammarresi, M and Silva, A and Vanegas, O and Gomes, C and Ponte-Sucre, A}, title = {G Protein-Coupled Receptors as Potential Intercellular Communication Mediators in Trypanosomatidae.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {812848}, pmid = {35651757}, issn = {2235-2988}, mesh = {*Calcitonin Gene-Related Peptide/pharmacology ; Cell Communication ; Humans ; *Leishmania/metabolism ; Receptor Activity-Modifying Proteins/metabolism ; Receptors, G-Protein-Coupled/metabolism ; Substance P/pharmacology ; }, abstract = {Detection and transduction of environmental signals, constitute a prerequisite for successful parasite invasion; i.e., Leishmania transmission, survival, pathogenesis and disease manifestation and dissemination, with diverse molecules functioning as inter-cellular signaling ligands. Receptors [i.e., G protein-coupled receptors (GPCRs)] and their associated transduction mechanisms, well conserved through evolution, specialize in this function. However, canonical GPCR-related signal transduction systems have not been described in Leishmania, although orthologs, with reduced domains and function, have been identified in Trypanosomatidae. These inter-cellular communication means seem to be essential for multicellular and unicellular organism's survival. GPCRs are flexible in their molecular architecture and may interact with the so-called receptor activity-modifying proteins (RAMPs), which modulate their function, changing GPCRs pharmacology, acting as chaperones and regulating signaling and/or trafficking in a receptor-dependent manner. In the skin, vasoactive- and neuro- peptides released in response to the noxious stimuli represented by the insect bite may trigger parasite physiological responses, for example, chemotaxis. For instance, in Leishmania (V.) braziliensis, sensory [Substance P, SP, chemoattractant] and autonomic [Vasoactive Intestinal Peptide, VIP, and Neuropeptide Y, NPY, chemorepellent] neuropeptides at physiological levels stimulate in vitro effects on parasite taxis. VIP and NPY chemotactic effects are impaired by their corresponding receptor antagonists, suggesting that the stimulated responses might be mediated by putative GPCRs (with essential conserved receptor domains); the effect of SP is blocked by [(D-Pro 2, D-Trp7,9]-Substance P (10[-6] M)] suggesting that it might be mediated by neurokinin-1 transmembrane receptors. Additionally, vasoactive molecules like Calcitonin Gene-Related Peptide [CGRP] and Adrenomedullin [AM], exert a chemorepellent effect and increase the expression of a 24 kDa band recognized in western blot analysis by (human-)-RAMP-2 antibodies. In-silico search oriented towards GPCRs-like receptors and signaling cascades detected a RAMP-2-aligned sequence corresponding to Leishmania folylpolyglutamate synthase and a RAMP-3 aligned protein, a hypothetical Leishmania protein with yet unknown function, suggesting that in Leishmania, CGRP and AM activities may be modulated by RAMP- (-2) and (-3) homologs. The possible presence of proteins and molecules potentially involved in GPCRs cascades, i.e., RAMPs, signpost conservation of ancient signaling systems associated with responses, fundamental for cell survival, (i.e., taxis and migration) and may constitute an open field for description of pharmacophores against Leishmania parasites.}, } @article {pmid35628404, year = {2022}, author = {Paradžik, T and Podgorski, II and Vojvoda Zeljko, T and Paradžik, M}, title = {Ancient Origins of Cytoskeletal Crosstalk: Spectraplakin-like Proteins Precede the Emergence of Cortical Microtubule Stabilization Complexes as Crosslinkers.}, journal = {International journal of molecular sciences}, volume = {23}, number = {10}, pages = {}, pmid = {35628404}, issn = {1422-0067}, mesh = {Actin Cytoskeleton/metabolism ; *Actins/metabolism ; Animals ; *Cytoskeleton/metabolism ; Microtubules/metabolism ; Phylogeny ; }, abstract = {Adhesion between cells and the extracellular matrix (ECM) is one of the prerequisites for multicellularity, motility, and tissue specialization. Focal adhesions (FAs) are defined as protein complexes that mediate signals from the ECM to major components of the cytoskeleton (microtubules, actin, and intermediate filaments), and their mutual communication determines a variety of cellular processes. In this study, human cytoskeletal crosstalk proteins were identified by comparing datasets with experimentally determined cytoskeletal proteins. The spectraplakin dystonin was the only protein found in all datasets. Other proteins (FAK, RAC1, septin 9, MISP, and ezrin) were detected at the intersections of FAs, microtubules, and actin cytoskeleton. Homology searches for human crosstalk proteins as queries were performed against a predefined dataset of proteomes. This analysis highlighted the importance of FA communication with the actin and microtubule cytoskeleton, as these crosstalk proteins exhibit the highest degree of evolutionary conservation. Finally, phylogenetic analyses elucidated the early evolutionary history of spectraplakins and cortical microtubule stabilization complexes (CMSCs) as model representatives of the human cytoskeletal crosstalk. While spectraplakins probably arose at the onset of opisthokont evolution, the crosstalk between FAs and microtubules is associated with the emergence of metazoans. The multiprotein complexes contributing to cytoskeletal crosstalk in animals gradually gained in complexity from the onset of metazoan evolution.}, } @article {pmid35626631, year = {2022}, author = {Paul, B and Sterner, ZR and Buchholz, DR and Shi, YB and Sachs, LM}, title = {Thyroid and Corticosteroid Signaling in Amphibian Metamorphosis.}, journal = {Cells}, volume = {11}, number = {10}, pages = {}, pmid = {35626631}, issn = {2073-4409}, mesh = {Adrenal Cortex Hormones ; Amphibians ; Animals ; *Metamorphosis, Biological/physiology ; *Thyroid Gland/metabolism ; Thyroid Hormones/metabolism ; Vertebrates/metabolism ; }, abstract = {In multicellular organisms, development is based in part on the integration of communication systems. Two neuroendocrine axes, the hypothalamic-pituitary-thyroid and the hypothalamic-pituitary-adrenal/interrenal axes, are central players in orchestrating body morphogenesis. In all vertebrates, the hypothalamic-pituitary-thyroid axis controls thyroid hormone production and release, whereas the hypothalamic-pituitary-adrenal/interrenal axis regulates the production and release of corticosteroids. One of the most salient effects of thyroid hormones and corticosteroids in post-embryonic developmental processes is their critical role in metamorphosis in anuran amphibians. Metamorphosis involves modifications to the morphological and biochemical characteristics of all larval tissues to enable the transition from one life stage to the next life stage that coincides with an ecological niche switch. This transition in amphibians is an example of a widespread phenomenon among vertebrates, where thyroid hormones and corticosteroids coordinate a post-embryonic developmental transition. The review addresses the functions and interactions of thyroid hormone and corticosteroid signaling in amphibian development (metamorphosis) as well as the developmental roles of these two pathways in vertebrate evolution.}, } @article {pmid35621103, year = {2022}, author = {Puzakov, MV and Puzakova, LV}, title = {[Prevalence, Diversity, and Evolution of L18 (DD37E) Transposons in the Genomes of Cnidarians].}, journal = {Molekuliarnaia biologiia}, volume = {56}, number = {3}, pages = {476-490}, doi = {10.31857/S0026898422030120}, pmid = {35621103}, issn = {0026-8984}, mesh = {Animals ; *Cnidaria/genetics ; *DNA Transposable Elements/genetics ; Prevalence ; }, abstract = {Transposable elements have a significant impact on the structure and functioning of multicellular genomes, and also serve as a source of new genes. Studying the diversity and evolution of transposable elements in different taxa is necessary for the fundamental understanding of their role in genomes. The Tc1/mariner elements are one of the most widespread and diverse groups of DNA transposons. In this work, the structure, distribution, diversity, and evolution of the L18 (DD37E) elements in the genomes of cnidarians (Cnidaria) were studied for the first time. As a result, it was found that the L18 group is an independent family (and not a subfamily of the TLE family, as previously thought) in the Tc1/mariner superfamily. Of the 51 detected elements, only four had potentially functional copies. It is assumed that the L18 transposons are of ancient origin, and, in addition, the elements found in the genomes of organisms of the Anthozoa and Hydrozoa classes do not come from a common ancestral transposon within the Cnidaria phylum. In organisms of the Hydrozoa class, L18 transposons appeared as a result of horizontal transfer at a later time period. An intraspecies comparison of the diversity of the L18 elements demonstrates high homogeneity with respect to "old" transposons, which have already lost their activity. At the same time, distant populations, as in the case of Hydra viridissima, have differences in the representation of DNA transposons and the number of copies. These data supplement the knowledge on the diversity and evolution of Tc1/mariner transposons and contribute to the study of the influence of mobile genetic elements on the evolution of multicellular organisms.}, } @article {pmid35588907, year = {2022}, author = {Udayantha, HMV and Samaraweera, AV and Liyanage, DS and Sandamalika, WMG and Lim, C and Yang, H and Lee, JH and Lee, S and Lee, J}, title = {Molecular characterization, antiviral activity, and UV-B damage responses of Caspase-9 from Amphiprion clarkii.}, journal = {Fish & shellfish immunology}, volume = {125}, number = {}, pages = {247-257}, doi = {10.1016/j.fsi.2022.05.023}, pmid = {35588907}, issn = {1095-9947}, mesh = {Animals ; Antiviral Agents ; Caspase 3 ; Caspase 9 ; *Cyprinidae ; *Perciformes ; Phylogeny ; Poly I-C/pharmacology ; }, abstract = {Apoptosis plays a vital role in maintaining cellular homeostasis in multicellular organisms. Caspase-9 (casp-9) is one of the major initiator caspases that induces apoptosis by activating downstream intrinsic apoptosis pathway genes. Here, we isolated the cDNA sequence (1992 bp) of caspase-9 from Amphiprion clarkii (Accasp-9) that consists of a 1305 bp coding region and encodes a 434 aa protein. In silico analysis showed that Accasp-9 has a theoretical isoelectric point of 5.81 and a molecular weight of 48.45 kDa. Multiple sequence alignment revealed that the CARD domain is located at the N-terminus, whereas the large P-20 and small P-10 domains are located at the C-terminus. Moreover, a highly conserved pentapeptide active site ([296]QACGG[301]), as well as histidine and cysteine active sites, are also retained at the C-terminus. In phylogenetic analysis, Accasp-9 formed a clade with casp-9 from different species, distinct from other caspases. Accasp-9 was highly expressed in the gill and intestine compared with other tissues analyzed in healthy A. clarkii. Accasp-9 expression was significantly elevated in the blood after stimulation with Vibrio harveyi and polyinosinic:polycytidylic acid (poly I:C; 12-48 h), but not with lipopolysaccharide. The nucleoprotein expression of the viral hemorrhagic septicemia virus was significantly reduced in Accasp-9 overexpressed fathead minnow (FHM) cells compared with that in the control. In addition, other in vitro assays revealed that cell apoptosis was significantly elevated in poly I:C and UV-B-treated Accasp-9 transfected FHM cells. However, H[248P] or C[298S] mutated Accasp-9 significantly reduced apoptosis in UV-B irradiated cells. Collectively, our results show that Accasp-9 might play a defensive role against invading pathogens and UV-B radiation and H[248] and C[298] active residues are significantly involved in apoptosis in teleosts.}, } @article {pmid35587048, year = {2022}, author = {Gardner, DS and Gray, C}, title = {Development and the art of nutritional maintenance.}, journal = {The British journal of nutrition}, volume = {128}, number = {5}, pages = {828-834}, pmid = {35587048}, issn = {1475-2662}, mesh = {Animals ; Nutritive Value ; *Nutrients ; *Energy Intake ; }, abstract = {Development from early conceptus to a complex, multi-cellular organism is a highly ordered process that is dependent on an adequate supply of nutrients. During this process, the pattern of organ growth is robust, driven by a genetic blueprint and matched to anticipated body mass with high precision and with built-in physiological reserve capacity. This apparent canalisation of the developmental process is particularly sensitive to variation in environmental stimuli, such as inappropriate drug or hormone exposure, or pattern of nutrient delivery. Significant variation in any of these factors can profoundly affect fetal and neonatal growth patterns, with later detriment for physiological function and/or reserve capacity of the resultant adult, with potential health impact. This paradigm shift in science has become known as the Developmental Origins of Health and Disease (DOHaD). Over the last 30 years, many animal and clinical studies have vastly expanded our fundamental knowledge of developmental biology, particularly in the context of later effects on health. In this horizons article, we discuss DOHaD through the lens of nutritional quality (e.g. micronutrient, amino acid, NSP intake). The concept of ‘Quality’ was considered undefinable by Robert Persig in his book, ‘Zen and the Art of Motorcycle Maintenance’. Here, development and the art of nutritional maintenance will define quality in terms of the pattern of nutrient intake, the quality of development and how each interact to influence later health outcomes.}, } @article {pmid35574025, year = {2022}, author = {Ritch, SJ and Telleria, CM}, title = {The Transcoelomic Ecosystem and Epithelial Ovarian Cancer Dissemination.}, journal = {Frontiers in endocrinology}, volume = {13}, number = {}, pages = {886533}, pmid = {35574025}, issn = {1664-2392}, mesh = {Carcinoma, Ovarian Epithelial ; *Ecosystem ; Epithelial Cells/metabolism ; Female ; Humans ; Neoplasm Recurrence, Local ; *Ovarian Neoplasms/therapy ; Tumor Microenvironment ; }, abstract = {Epithelial ovarian cancer (EOC) is considered the deadliest gynecological disease and is normally diagnosed at late stages, at which point metastasis has already occurred. Throughout disease progression, EOC will encounter various ecosystems and the communication between cancer cells and these microenvironments will promote the survival and dissemination of EOC. The primary tumor is thought to develop within the ovaries or the fallopian tubes, both of which provide a microenvironment with high risk of causing DNA damage and enhanced proliferation. EOC disseminates by direct extension from the primary tumors, as single cells or multicellular aggregates. Under the influence of cellular and non-cellular factors, EOC spheroids use the natural flow of peritoneal fluid to reach distant organs within the peritoneal cavity. These cells can then implant and seed distant organs or tissues, which develop rapidly into secondary tumor nodules. The peritoneal tissue and the omentum are two common sites of EOC metastasis, providing a microenvironment that supports EOC invasion and survival. Current treatment for EOC involves debulking surgery followed by platinum-taxane combination chemotherapy; however, most patients will relapse with a chemoresistant disease with tumors developed within the peritoneum. Therefore, understanding the role of the unique microenvironments that promote EOC transcoelomic dissemination is important in improving patient outcomes from this disease. In this review article, we address the process of ovarian cancer cellular fate at the site of its origin in the secretory cells of the fallopian tube or in the ovarian surface epithelial cells, their detachment process, how the cells survive in the peritoneal fluid avoiding cell death triggers, and how cancer- associated cells help them in the process. Finally, we report the mechanisms used by the ovarian cancer cells to adhere and migrate through the mesothelial monolayer lining the peritoneum. We also discuss the involvement of the transcoelomic ecosystem on the development of chemoresistance of EOC.}, } @article {pmid35572413, year = {2022}, author = {Zhang, J and Shen, N and Li, C and Xiang, X and Liu, G and Gui, Y and Patev, S and Hibbett, DS and Barry, K and Andreopoulos, W and Lipzen, A and Riley, R and He, G and Yan, M and Grigoriev, IV and Shan Kwan, H and Kit Cheung, M and Bian, Y and Xiao, Y}, title = {Population genomics provides insights into the genetic basis of adaptive evolution in the mushroom-forming fungus Lentinula edodes.}, journal = {Journal of advanced research}, volume = {38}, number = {}, pages = {91-106}, pmid = {35572413}, issn = {2090-1224}, mesh = {*Agaricales/genetics ; Genome ; Genome-Wide Association Study ; Metagenomics ; *Shiitake Mushrooms/genetics ; }, abstract = {INTRODUCTION: Mushroom-forming fungi comprise diverse species that develop complex multicellular structures. In cultivated species, both ecological adaptation and artificial selection have driven genome evolution. However, little is known about the connections among genotype, phenotype and adaptation in mushroom-forming fungi.

OBJECTIVES: This study aimed to (1) uncover the population structure and demographic history of Lentinula edodes, (2) dissect the genetic basis of adaptive evolution in L. edodes, and (3) determine if genes related to fruiting body development are involved in adaptive evolution.

METHODS: We analyzed genomes and fruiting body-related traits (FBRTs) in 133 L. edodes strains and conducted RNA-seq analysis of fruiting body development in the YS69 strain. Combined methods of genomic scan for divergence, genome-wide association studies (GWAS), and RNA-seq were used to dissect the genetic basis of adaptive evolution.

RESULTS: We detected three distinct subgroups of L. edodes via single nucleotide polymorphisms, which showed robust phenotypic and temperature response differentiation and correlation with geographical distribution. Demographic history inference suggests that the subgroups diverged 36,871 generations ago. Moreover, L. edodes cultivars in China may have originated from the vicinity of Northeast China. A total of 942 genes were found to be related to genetic divergence by genomic scan, and 719 genes were identified to be candidates underlying FBRTs by GWAS. Integrating results of genomic scan and GWAS, 80 genes were detected to be related to phenotypic differentiation. A total of 364 genes related to fruiting body development were involved in genetic divergence and phenotypic differentiation.

CONCLUSION: Adaptation to the local environment, especially temperature, triggered genetic divergence and phenotypic differentiation of L. edodes. A general model for genetic divergence and phenotypic differentiation during adaptive evolution in L. edodes, which involves in signal perception and transduction, transcriptional regulation, and fruiting body morphogenesis, was also integrated here.}, } @article {pmid35570706, year = {2022}, author = {Heinz, MC and Peters, NA and Oost, KC and Lindeboom, RGH and van Voorthuijsen, L and Fumagalli, A and van der Net, MC and de Medeiros, G and Hageman, JH and Verlaan-Klink, I and Borel Rinkes, IHM and Liberali, P and Gloerich, M and van Rheenen, J and Vermeulen, M and Kranenburg, O and Snippert, HJG}, title = {Liver Colonization by Colorectal Cancer Metastases Requires YAP-Controlled Plasticity at the Micrometastatic Stage.}, journal = {Cancer research}, volume = {82}, number = {10}, pages = {1953-1968}, pmid = {35570706}, issn = {1538-7445}, mesh = {Animals ; *Colorectal Neoplasms/pathology ; Humans ; *Liver Neoplasms/metabolism ; Mice ; Neoplasm Micrometastasis/pathology ; Neoplastic Stem Cells/pathology ; }, abstract = {UNLABELLED: Micrometastases of colorectal cancer can remain dormant for years prior to the formation of actively growing, clinically detectable lesions (i.e., colonization). A better understanding of this step in the metastatic cascade could help improve metastasis prevention and treatment. Here we analyzed liver specimens of patients with colorectal cancer and monitored real-time metastasis formation in mouse livers using intravital microscopy to reveal that micrometastatic lesions are devoid of cancer stem cells (CSC). However, lesions that grow into overt metastases demonstrated appearance of de novo CSCs through cellular plasticity at a multicellular stage. Clonal outgrowth of patient-derived colorectal cancer organoids phenocopied the cellular and transcriptomic changes observed during in vivo metastasis formation. First, formation of mature CSCs occurred at a multicellular stage and promoted growth. Conversely, failure of immature CSCs to generate more differentiated cells arrested growth, implying that cellular heterogeneity is required for continuous growth. Second, early-stage YAP activity was required for the survival of organoid-forming cells. However, subsequent attenuation of early-stage YAP activity was essential to allow for the formation of cell type heterogeneity, while persistent YAP signaling locked micro-organoids in a cellularly homogenous and growth-stalled state. Analysis of metastasis formation in mouse livers using single-cell RNA sequencing confirmed the transient presence of early-stage YAP activity, followed by emergence of CSC and non-CSC phenotypes, irrespective of the initial phenotype of the metastatic cell of origin. Thus, establishment of cellular heterogeneity after an initial YAP-controlled outgrowth phase marks the transition to continuously growing macrometastases.

SIGNIFICANCE: Characterization of the cell type dynamics, composition, and transcriptome of early colorectal cancer liver metastases reveals that failure to establish cellular heterogeneity through YAP-controlled epithelial self-organization prohibits the outgrowth of micrometastases. See related commentary by LeBleu, p. 1870.}, } @article {pmid35563757, year = {2022}, author = {Stange, K and Keric, A and Friese, A and Röntgen, M}, title = {Preparation of Spheroids from Primary Pig Cells in a Mid-Scale Bioreactor Retaining Their Myogenic Potential.}, journal = {Cells}, volume = {11}, number = {9}, pages = {}, pmid = {35563757}, issn = {2073-4409}, mesh = {Animals ; Bioreactors ; Cell Differentiation ; *Muscle Development ; *Muscle Fibers, Skeletal ; Swine ; }, abstract = {Three-dimensional cell culture techniques mimic the in vivo cell environment more adequately than flat surfaces. Spheroids are multicellular aggregates and we aimed to produce scaffold-free spheroids of myogenic origin, called myospheres, using a mid-scale incubator and bioreactor hybrid. For the first time, we obtained spheroids from primary porcine muscle cells (PMCs) with this technology and compared their morphology and growth parameters, marker expression, and myogenic potential to C2C12-derived spheroids. Both cell types were able to form round-shaped spheroids in the bioreactor already after 24 h. The mean diameter of the C2C12 spheroids (44.6 µm) was larger than that of the PMCs (32.7 µm), and the maximum diameter exceeded 1 mm. C2C12 cells formed less aggregates than PMCs with a higher packing density (cell nuclei/mm[2]). After dissociation from the spheroids, C2C12 cells and PMCs started to proliferate again and were able to differentiate into the myogenic lineage, as shown by myotube formation and the expression of F-Actin, Desmin, MyoG, and Myosin. For C2C12, multinucleated syncytia and Myosin expression were observed in spheroids, pointing to accelerated myogenic differentiation. In conclusion, the mid-scale incubator and bioreactor system is suitable for spheroid formation and cultivation from primary muscle cells while preserving their myogenic potential.}, } @article {pmid35551578, year = {2022}, author = {Eskandari, E and Eaves, CJ}, title = {Paradoxical roles of caspase-3 in regulating cell survival, proliferation, and tumorigenesis.}, journal = {The Journal of cell biology}, volume = {221}, number = {6}, pages = {}, pmid = {35551578}, issn = {1540-8140}, mesh = {Apoptosis/genetics ; *Carcinogenesis/genetics ; *Caspase 3/physiology ; *Cell Proliferation ; *Cell Survival/genetics ; Humans ; Saccharomyces cerevisiae ; }, abstract = {Caspase-3 is a widely expressed member of a conserved family of proteins, generally recognized for their activated proteolytic roles in the execution of apoptosis in cells responding to specific extrinsic or intrinsic inducers of this mode of cell death. However, accumulating evidence indicates that caspase-3 also plays key roles in regulating the growth and homeostatic maintenance of both normal and malignant cells and tissues in multicellular organisms. Given that yeast possess an ancestral caspase-like gene suggests that the caspase-3 protein may have acquired different functions later during evolution to better meet the needs of more complex multicellular organisms, but without necessarily losing all of the functions of its ancestral yeast precursor. This review provides an update on what has been learned about these interesting dichotomous roles of caspase-3, their evolution, and their potential relevance to malignant as well as normal cell biology.}, } @article {pmid35530508, year = {2022}, author = {de la Fuente, M and Novo, M}, title = {Understanding Diversity, Evolution, and Structure of Small Heat Shock Proteins in Annelida Through in Silico Analyses.}, journal = {Frontiers in physiology}, volume = {13}, number = {}, pages = {817272}, pmid = {35530508}, issn = {1664-042X}, abstract = {Small heat shock proteins (sHsps) are oligomeric stress proteins characterized by an α-crystallin domain (ACD). These proteins are localized in different subcellular compartments and play critical roles in the stress physiology of tissues, organs, and whole multicellular eukaryotes. They are ubiquitous proteins found in all living organisms, from bacteria to mammals, but they have never been studied in annelids. Here, a data set of 23 species spanning the annelid tree of life, including mostly transcriptomes but also two genomes, was interrogated and 228 novel putative sHsps were identified and manually curated. The analysis revealed very high protein diversity and showed that a significant number of sHsps have a particular dimeric architecture consisting of two tandemly repeated ACDs. The phylogenetic analysis distinguished three main clusters, two of them containing both monomeric sHsps, and ACDs located downstream in the dimeric sHsps, and the other one comprising the upstream ACDs from those dimeric forms. Our results support an evolutionary history of these proteins based on duplication events prior to the Spiralia split. Monomeric sHsps 76) were further divided into five subclusters. Physicochemical properties, subcellular location predictions, and sequence conservation analyses provided insights into the differentiating elements of these putative functional groups. Strikingly, three of those subclusters included sHsps with features typical of metazoans, while the other two presented characteristics resembling non-metazoan proteins. This study provides a solid background for further research on the diversity, evolution, and function in the family of the sHsps. The characterized annelid sHsps are disclosed as essential for improving our understanding of this important family of proteins and their pleotropic functions. The features and the great diversity of annelid sHsps position them as potential powerful molecular biomarkers of environmental stress for acting as prognostic tool in a diverse range of environments.}, } @article {pmid35514085, year = {2022}, author = {Yuan, F and Wang, X and Zhao, B and Xu, X and Shi, M and Leng, B and Dong, X and Lu, C and Feng, Z and Guo, J and Han, G and Zhang, H and Huang, J and Chen, M and Wang, BS}, title = {The genome of the recretohalophyte Limonium bicolor provides insights into salt gland development and salinity adaptation during terrestrial evolution.}, journal = {Molecular plant}, volume = {15}, number = {6}, pages = {1024-1044}, doi = {10.1016/j.molp.2022.04.011}, pmid = {35514085}, issn = {1752-9867}, mesh = {Animals ; *Arabidopsis ; Plant Leaves/genetics ; *Plumbaginaceae/genetics ; Salinity ; Salt Gland ; Salt Tolerance/genetics ; Salt-Tolerant Plants/genetics ; }, abstract = {Halophytes have evolved specialized strategies to cope with high salinity. The extreme halophyte sea lavender (Limonium bicolor) lacks trichomes but possesses salt glands on its epidermis that can excrete harmful ions, such as sodium, to avoid salt damage. Here, we report a high-quality, 2.92-Gb, chromosome-scale L. bicolor genome assembly based on a combination of Illumina short reads, single-molecule, real-time long reads, chromosome conformation capture (Hi-C) data, and Bionano genome maps, greatly enriching the genomic information on recretohalophytes with multicellular salt glands. Although the L. bicolor genome contains genes that show similarity to trichome fate genes from Arabidopsis thaliana, it lacks homologs of the decision fate genes GLABRA3, ENHANCER OF GLABRA3, GLABRA2, TRANSPARENT TESTA GLABRA2, and SIAMESE, providing a molecular explanation for the absence of trichomes in this species. We identified key genes (LbHLH and LbTTG1) controlling salt gland development among classical trichome homologous genes and confirmed their roles by showing that their mutations markedly disrupted salt gland initiation, salt secretion, and salt tolerance, thus offering genetic support for the long-standing hypothesis that salt glands and trichomes may share a common origin. In addition, a whole-genome duplication event occurred in the L. bicolor genome after its divergence from Tartary buckwheat and may have contributed to its adaptation to high salinity. The L. bicolor genome resource and genetic evidence reported in this study provide profound insights into plant salt tolerance mechanisms that may facilitate the engineering of salt-tolerant crops.}, } @article {pmid35504284, year = {2022}, author = {Reyes-Rivera, J and Wu, Y and Guthrie, BGH and Marletta, MA and King, N and Brunet, T}, title = {Nitric oxide signaling controls collective contractions in a colonial choanoflagellate.}, journal = {Current biology : CB}, volume = {32}, number = {11}, pages = {2539-2547.e5}, doi = {10.1016/j.cub.2022.04.017}, pmid = {35504284}, issn = {1879-0445}, support = {/HHMI/Howard Hughes Medical Institute/United States ; R01 GM127854/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Choanoflagellata/metabolism ; Cyclic GMP/metabolism ; Guanylate Cyclase/genetics ; Nitric Oxide/metabolism ; Nitric Oxide Synthase/genetics/metabolism ; Signal Transduction/physiology ; }, abstract = {Although signaling by the gaseous molecule nitric oxide (NO) regulates key physiological processes in animals, including contractility,[1-3] immunity,[4][,][5] development,[6-9] and locomotion,[10][,][11] the early evolution of animal NO signaling remains unclear. To reconstruct the role of NO in the animal stem lineage, we set out to study NO signaling in choanoflagellates, the closest living relatives of animals.[12] In animals, NO produced by the nitric oxide synthase (NOS) canonically signals through cGMP by activating soluble guanylate cyclases (sGCs).[13][,][14] We surveyed the distribution of the NO signaling pathway components across the diversity of choanoflagellates and found three species that express NOS (of either bacterial or eukaryotic origin), sGCs, and downstream genes previously shown to be involved in the NO/cGMP pathway. One of the species coexpressing sGCs and a bacterial-type NOS, Choanoeca flexa, forms multicellular sheets that undergo collective contractions controlled by cGMP.[15] We found that treatment with NO induces cGMP synthesis and contraction in C. flexa. Biochemical assays show that NO directly binds C. flexa sGC1 and stimulates its cyclase activity. The NO/cGMP pathway acts independently from other inducers of C. flexa contraction, including mechanical stimuli and heat, but sGC activity is required for contractions induced by light-to-dark transitions. The output of NO signaling in C. flexa-contractions resulting in a switch from feeding to swimming-resembles the effect of NO in sponges[1-3] and cnidarians,[11][,][16][,][17] where it interrupts feeding and activates contractility. These data provide insights into the biology of the first animals and the evolution of NO signaling.}, } @article {pmid35486699, year = {2022}, author = {Staps, M and Tarnita, CE}, title = {When being flexible matters: Ecological underpinnings for the evolution of collective flexibility and task allocation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {119}, number = {18}, pages = {e2116066119}, pmid = {35486699}, issn = {1091-6490}, mesh = {Animals ; Ants ; *Behavior, Animal ; *Biological Evolution ; Ecology ; Humans ; *Social Behavior ; }, abstract = {Task allocation is a central feature of collective organization. Living collective systems, such as multicellular organisms or social insect colonies, have evolved diverse ways to allocate individuals to different tasks, ranging from rigid, inflexible task allocation that is not adjusted to changing circumstances to more fluid, flexible task allocation that is rapidly adjusted to the external environment. While the mechanisms underlying task allocation have been intensely studied, it remains poorly understood whether differences in the flexibility of task allocation can be viewed as adaptive responses to different ecological contexts—for example, different degrees of temporal variability. Motivated by this question, we develop an analytically tractable mathematical framework to explore the evolution of task allocation in dynamic environments. We find that collective flexibility is not necessarily always adaptive, and fails to evolve in environments that change too slowly (relative to how long tasks can be left unattended) or too quickly (relative to how rapidly task allocation can be adjusted). We further employ the framework to investigate how environmental variability impacts the internal organization of task allocation, which allows us to propose adaptive explanations for some puzzling empirical observations, such as seemingly unnecessary task switching under constant environmental conditions, apparent task specialization without efficiency benefits, and high levels of individual inactivity. Altogether, this work provides a general framework for probing the evolved diversity of task allocation strategies in nature and reinforces the idea that considering a system’s ecology is crucial to explaining its collective organization.}, } @article {pmid35484218, year = {2022}, author = {Farkas, Z and Kovács, K and Sarkadi, Z and Kalapis, D and Fekete, G and Birtyik, F and Ayaydin, F and Molnár, C and Horváth, P and Pál, C and Papp, B}, title = {Gene loss and compensatory evolution promotes the emergence of morphological novelties in budding yeast.}, journal = {Nature ecology & evolution}, volume = {6}, number = {6}, pages = {763-773}, pmid = {35484218}, issn = {2397-334X}, support = {098016/Z/11/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Mutation ; Phenotype ; Saccharomyces cerevisiae/genetics ; *Saccharomycetales/genetics ; }, abstract = {Deleterious mutations are generally considered to be irrelevant for morphological evolution. However, they could be compensated by conditionally beneficial mutations, thereby providing access to new adaptive paths. Here we use high-dimensional phenotyping of laboratory-evolved budding yeast lineages to demonstrate that new cellular morphologies emerge exceptionally rapidly as a by-product of gene loss and subsequent compensatory evolution. Unexpectedly, the capacities for invasive growth, multicellular aggregation and biofilm formation also spontaneously evolve in response to gene loss. These multicellular phenotypes can be achieved by diverse mutational routes and without reactivating the canonical regulatory pathways. These ecologically and clinically relevant traits originate as pleiotropic side effects of compensatory evolution and have no obvious utility in the laboratory environment. The extent of morphological diversity in the evolved lineages is comparable to that of natural yeast isolates with diverse genetic backgrounds and lifestyles. Finally, we show that both the initial gene loss and subsequent compensatory mutations contribute to new morphologies, with their synergistic effects underlying specific morphological changes. We conclude that compensatory evolution is a previously unrecognized source of morphological diversity and phenotypic novelties.}, } @article {pmid35483597, year = {2022}, author = {Wang, B and Zhu, F and Shi, Z and Huang, Z and Sun, R and Wang, Q and Ouyang, G and Ji, W}, title = {Molecular characteristics, polymorphism and expression analysis of mhc Ⅱ in yellow catfish(pelteobagrus fulvidraco)responding to Flavobacterium columnare infection.}, journal = {Fish & shellfish immunology}, volume = {125}, number = {}, pages = {90-100}, doi = {10.1016/j.fsi.2022.04.036}, pmid = {35483597}, issn = {1095-9947}, mesh = {Animals ; *Catfishes ; Fish Proteins/chemistry ; Flavobacterium/genetics ; Phylogeny ; RNA, Messenger/metabolism ; }, abstract = {The major histocompatibility complex (MHC) is an important component of the immune system of vertebrates, which plays a vital role in presenting extrinsic antigens. In this study, we cloned and characterized the mhc ⅡA and mhc ⅡB genes of yellow catfish Pelteobagrus fulvidraco. The open reading frames (ORFs) of mhc ⅡA and mhc ⅡB genes were 708 bp and 747bp in length, encoding 235 and 248 amino acids, respectively. The structure of mhc ⅡA and mhc ⅡB includes a signal peptide, an α1/β1 domain, an α2/β2 domain, a transmembrane region and a cytoplasmic region. Homologous identity analysis revealed that both mhc ⅡA and mhc ⅡB shared high protein sequence similarity with that of Chinese longsnout catfish Leiocassis longirostris. mhc ⅡA and mhc ⅡB showed similar expression patterns in different tissues, with the higher expression level in spleen, head kidney and gill and lower expression in liver, stomach, gall bladder and heart. The mRNA expression level of mhc ⅡA and mhc ⅡB in different embryonic development stages also showed the similar trends. The higher expression was detected from fertilized egg to 32 cell stage, low expression from multicellular period to 3 days post hatching (dph), and then the expression increased to a higher level from 4 dph to 14 dph. The mRNA expression levels of mhc ⅡA and mhc ⅡB were significantly up-regulated not only in the body kidney and spleen, but also in the midgut, hindgut, liver and gill after challenge of Flavobacterium columnare. The results suggest that Mhc Ⅱ plays an important role in the anti-infection process of yellow catfish P. fulvidraco.}, } @article {pmid35472432, year = {2022}, author = {Chaigne, A and Brunet, T}, title = {Incomplete abscission and cytoplasmic bridges in the evolution of eukaryotic multicellularity.}, journal = {Current biology : CB}, volume = {32}, number = {8}, pages = {R385-R397}, doi = {10.1016/j.cub.2022.03.021}, pmid = {35472432}, issn = {1879-0445}, support = {201334/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; *Biological Evolution ; Cytoplasm ; Cytosol ; *Eukaryota ; Eukaryotic Cells ; }, abstract = {The textbook view of cell division terminates with the final separation of the two daughter cells in the process called abscission. However, in contrast to this classical view, a variety of cell types in multicellular organisms are connected through cytoplasmic bridges, which most often form by incomplete abscission or - more rarely - by local fusion of plasma membranes. In this review, we survey the distribution, function, and formation of cytoplasmic bridges across the eukaryotic tree of life. We find that cytoplasmic bridges are widespread, and were likely ancestrally present, in almost all lineages of eukaryotes with clonal multicellularity - including the five 'complex multicellular' lineages: animals, fungi, land plants, red algae, and brown algae. In animals, cytoplasmic bridges resulting from incomplete abscission are ubiquitous in the germline and common in pluripotent cell types. Although cytoplasmic bridges have been less studied than other structural mediators of multicellularity (such as adhesion proteins and extracellular matrix), we propose that they have played a pivotal role in the repeated evolution of eukaryotic clonal multicellularity - possibly by first performing a structural role and later by allowing exchange of nutrients and/or intercellular communication, which notably buffered cell-cell competition by averaging gene expression. Bridges were eventually lost from many animal tissues in concert with the evolution of spatial cell differentiation, cell motility within the organism, and other mechanisms for intercellular distribution of signals and metabolites. Finally, we discuss the molecular basis for the evolution of incomplete abscission and examine the alternative hypotheses of single or multiple origins.}, } @article {pmid35470227, year = {2022}, author = {Mulcahey, PJ and Chen, Y and Driscoll, N and Murphy, BB and Dickens, OO and Johnson, ATC and Vitale, F and Takano, H}, title = {Multimodal, Multiscale Insights into Hippocampal Seizures Enabled by Transparent, Graphene-Based Microelectrode Arrays.}, journal = {eNeuro}, volume = {9}, number = {3}, pages = {}, pmid = {35470227}, issn = {2373-2822}, support = {R21 NS106434/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; *Epilepsy, Temporal Lobe ; *Graphite ; Hippocampus ; Mice ; Microelectrodes ; Seizures ; }, abstract = {Hippocampal seizures are a defining feature of mesial temporal lobe epilepsy (MTLE). Area CA1 of the hippocampus is commonly implicated in the generation of seizures, which may occur because of the activity of endogenous cell populations or of inputs from other regions within the hippocampal formation. Simultaneously observing activity at the cellular and network scales in vivo remains challenging. Here, we present a novel technology for simultaneous electrophysiology and multicellular calcium imaging of CA1 pyramidal cells (PCs) in mice enabled by a transparent graphene-based microelectrode array (Gr MEA). We examine PC firing at seizure onset, oscillatory coupling, and the dynamics of the seizure traveling wave as seizures evolve. Finally, we couple features derived from both modalities to predict the speed of the traveling wave using bootstrap aggregated regression trees. Analysis of the most important features in the regression trees suggests a transition among states in the evolution of hippocampal seizures.}, } @article {pmid35468249, year = {2022}, author = {Melnikov, NP and Bolshakov, FV and Frolova, VS and Skorentseva, KV and Ereskovsky, AV and Saidova, AA and Lavrov, AI}, title = {Tissue homeostasis in sponges: Quantitative analysis of cell proliferation and apoptosis.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {338}, number = {6}, pages = {360-381}, doi = {10.1002/jez.b.23138}, pmid = {35468249}, issn = {1552-5015}, mesh = {Animals ; *Apoptosis ; Cell Proliferation ; Homeostasis ; *Signal Transduction ; }, abstract = {Tissues of multicellular animals are maintained due to a tight balance between cell proliferation and programmed cell death. Sponges are early branching metazoans essential to understanding the key mechanisms of tissue homeostasis. This article is dedicated to the comparative analysis of proliferation and apoptosis in intact tissues of two sponges, Halisarca dujardinii (class Demospongiae) and Leucosolenia variabilis (class Calcarea). Labeled nucleotides EdU and anti-phosphorylated histone 3 antibodies reveal a considerable number of cycling cells in intact tissues of both species. Quantitative DNA staining reveals the classic cell cycle distribution curve. The main type of cycling cells are choanocytes - flagellated cells of the aquiferous system. The rate of proliferation remains constant throughout various areas of sponge bodies that contain choanocytes. The EdU tracking experiments conducted in H. dujardinii indicate that choanocytes may give rise to mesohyl cells through migration. The number of apoptotic cells in tissues of both species is insignificant, although being comparable to the renewing tissues of other animals. In vivo studies with tetramethylrhodamine ethyl ester and CellEvent Caspase-3/7 indicate that apoptosis might be independent of mitochondrial outer membrane permeabilization. Altogether, a combination of confocal laser scanning microscopy and flow cytometry provides a quantitative description of cell proliferation and apoptosis in sponges displaying either rapid growth or cell turnover.}, } @article {pmid35421922, year = {2022}, author = {Nozaki, H and Mori, F and Tanaka, Y and Matsuzaki, R and Yamaguchi, H and Kawachi, M}, title = {Cryopreservation of vegetative cells and zygotes of the multicellular volvocine green alga Gonium pectorale.}, journal = {BMC microbiology}, volume = {22}, number = {1}, pages = {103}, pmid = {35421922}, issn = {1471-2180}, mesh = {*Chlorophyta ; Cryopreservation ; Nitrogen ; Phylogeny ; *Zygote ; }, abstract = {BACKGROUND: Colonial and multicellular volvocine green algae have been extensively studied recently in various fields of the biological sciences. However, only one species (Pandorina morum) has been cryopreserved in public culture collections.

RESULTS: Here, we investigated conditions for cryopreservation of the multicellular volvocine alga Gonium pectorale using vegetative colonies or cells and zygotes. Rates of vegetative cell survival in a G. pectorale strain after two-step cooling and freezing in liquid nitrogen were compared between different concentrations (3% and 6%) of the cryoprotectant N,N-dimethylformamide (DMF) and two types of tubes (0.2-mL polymerase chain reaction tubes and 2-mL cryotubes) used for cryopreservation. Among the four conditions investigated, the highest rate of survival [2.7 ± 3.6% (0.54-10%) by the most probable number (MPN) method] was obtained when 2.0-mL cryotubes containing 1.0 mL of culture samples with 6% DMF were subjected to cryogenic treatment. Using these optimized cryopreservation conditions, survival rates after freezing in liquid nitrogen were examined for twelve other strains of G. pectorale and twelve strains of five other Gonium species. We obtained ≥ 0.1% MPN survival in nine of the twelve G. pectorale strains tested. However, < 0.1% MPN survival was detected in eleven of twelve strains of five other Gonium species. In total, ten cryopreserved strains of G. pectorale were newly established in the Microbial Culture Collection at the National Institute for Environmental Studies. Although the cryopreservation of zygotes of volvocine algae has not been previously reported, high rates (approximately 60%) of G. pectorale zygote germination were observed after thawing zygotes that had been cryopreserved with 5% or 10% methanol as the cryoprotectant during two-step cooling and freezing in liquid nitrogen.

CONCLUSIONS: The present study demonstrated that cryopreservation of G. pectorale is possible with 6% DMF as a cryoprotectant and 1.0-mL culture samples in 2.0-mL cryotubes subjected to two-step cooling in a programmable freezer.}, } @article {pmid35420439, year = {2022}, author = {Rohkin Shalom, S and Weiss, B and Lalzar, M and Kaltenpoth, M and Chiel, E}, title = {Abundance and Localization of Symbiotic Bacterial Communities in the Fly Parasitoid Spalangia cameroni.}, journal = {Applied and environmental microbiology}, volume = {88}, number = {9}, pages = {e0254921}, pmid = {35420439}, issn = {1098-5336}, mesh = {Animals ; Enterobacteriaceae/genetics ; Female ; *Gammaproteobacteria ; In Situ Hybridization, Fluorescence ; Male ; *Rickettsia/genetics ; Symbiosis/physiology ; *Wasps/microbiology ; *Wolbachia/physiology ; }, abstract = {Multicellular eukaryotes often host multiple microbial symbionts that may cooperate or compete for host resources, such as space and nutrients. Here, we studied the abundances and localization of four bacterial symbionts, Rickettsia, Wolbachia, Sodalis, and Arsenophonus, in the parasitic wasp Spalangia cameroni. Using quantitative PCR (qPCR), we measured the symbionts' titers in wasps that harbor different combinations of these symbionts. We found that the titer of each symbiont decreased as the number of symbiont species in the community increased. Symbionts' titers were higher in females than in males. Rickettsia was the most abundant symbiont in all the communities, followed by Sodalis and Wolbachia. The titers of these three symbionts were positively correlated in some of the colonies. Fluorescence in situ hybridization was in line with the qPCR results: Rickettsia, Wolbachia, and Sodalis were observed in high densities in multiple organs, including brain, muscles, gut, Malpighian tubules, fat body, ovaries, and testes, while Arsenophonus was localized to fewer organs and in lower densities. Sodalis and Arsenophonus were observed in ovarian follicle cells but not within oocytes or laid eggs. This study highlights the connection between symbionts' abundance and localization. We discuss the possible connections between our findings to symbiont transmission success. IMPORTANCE Many insects carry intracellular bacterial symbionts (bacteria that reside within the cells of the insect). When multiple symbiont species cohabit in a host, they may compete or cooperate for space, nutrients, and transmission, and the nature of such interactions would be reflected in the abundance of each symbiont species. Given the widespread occurrence of coinfections with maternally transmitted symbionts in insects, it is important to learn more about how they interact, where they are localized, and how these two aspects affect their co-occurrence within individual insects. Here, we studied the abundance and the localization of four symbionts, Rickettsia, Wolbachia, Sodalis, and Arsenophonus, that cohabit the parasitic wasp Spalangia cameroni. We found that symbionts' titers differed between symbiotic communities. These results were corroborated by microscopy, which shows differential localization patterns. We discuss the findings in the contexts of community ecology, possible symbiont-symbiont interactions, and host control mechanisms that may shape the symbiotic community structure.}, } @article {pmid35417559, year = {2022}, author = {Kambayashi, C and Kakehashi, R and Sato, Y and Mizuno, H and Tanabe, H and Rakotoarison, A and Künzel, S and Furuno, N and Ohshima, K and Kumazawa, Y and Nagy, ZT and Mori, A and Allison, A and Donnellan, SC and Ota, H and Hoso, M and Yanagida, T and Sato, H and Vences, M and Kurabayashi, A}, title = {Geography-Dependent Horizontal Gene Transfer from Vertebrate Predators to Their Prey.}, journal = {Molecular biology and evolution}, volume = {39}, number = {4}, pages = {}, pmid = {35417559}, issn = {1537-1719}, mesh = {Animals ; Cattle ; *Gene Transfer, Horizontal ; Geography ; *Parasites/genetics ; Phylogeny ; Predatory Behavior ; Retroelements ; Vertebrates/genetics ; }, abstract = {Horizontal transfer (HT) of genes between multicellular animals, once thought to be extremely rare, is being more commonly detected, but its global geographic trend and transfer mechanism have not been investigated. We discovered a unique HT pattern of Bovine-B (BovB) LINE retrotransposons in vertebrates, with a bizarre transfer direction from predators (snakes) to their prey (frogs). At least 54 instances of BovB HT were detected, which we estimate to have occurred across time between 85 and 1.3 Ma. Using comprehensive transcontinental sampling, our study demonstrates that BovB HT is highly prevalent in one geographical region, Madagascar, suggesting important regional differences in the occurrence of HTs. We discovered parasite vectors that may plausibly transmit BovB and found that the proportion of BovB-positive parasites is also high in Madagascar where BovB thus might be physically transported by parasites to diverse vertebrates, potentially including humans. Remarkably, in two frog lineages, BovB HT occurred after migration from a non-HT area (Africa) to the HT hotspot (Madagascar). These results provide a novel perspective on how the prevalence of parasites influences the occurrence of HT in a region, similar to pathogens and their vectors in some endemic diseases.}, } @article {pmid35409376, year = {2022}, author = {Kasperski, A}, title = {Life Entrapped in a Network of Atavistic Attractors: How to Find a Rescue.}, journal = {International journal of molecular sciences}, volume = {23}, number = {7}, pages = {}, pmid = {35409376}, issn = {1422-0067}, mesh = {Cell Physiological Phenomena ; Cell Transformation, Neoplastic/metabolism ; *Energy Metabolism ; Humans ; Mitochondria/metabolism ; *Neoplasms/metabolism ; }, abstract = {In view of unified cell bioenergetics, cell bioenergetic problems related to cell overenergization can cause excessive disturbances in current cell fate and, as a result, lead to a change of cell-fate. At the onset of the problem, cell overenergization of multicellular organisms (especially overenergization of mitochondria) is solved inter alia by activation and then stimulation of the reversible Crabtree effect by cells. Unfortunately, this apparently good solution can also lead to a much bigger problem when, despite the activation of the Crabtree effect, cell overenergization persists for a long time. In such a case, cancer transformation, along with the Warburg effect, may occur to further reduce or stop the charging of mitochondria by high-energy molecules. Understanding the phenomena of cancer transformation and cancer development has become a real challenge for humanity. To date, many models have been developed to understand cancer-related mechanisms. Nowadays, combining all these models into one coherent universal model of cancer transformation and development can be considered a new challenge. In this light, the aim of this article is to present such a potentially universal model supported by a proposed new model of cellular functionality evolution. The methods of fighting cancer resulting from unified cell bioenergetics and the two presented models are also considered.}, } @article {pmid35406795, year = {2022}, author = {Zschüntzsch, J and Meyer, S and Shahriyari, M and Kummer, K and Schmidt, M and Kummer, S and Tiburcy, M}, title = {The Evolution of Complex Muscle Cell In Vitro Models to Study Pathomechanisms and Drug Development of Neuromuscular Disease.}, journal = {Cells}, volume = {11}, number = {7}, pages = {}, pmid = {35406795}, issn = {2073-4409}, mesh = {Coculture Techniques ; Drug Development ; Humans ; Muscle Cells ; *Neuromuscular Diseases/drug therapy ; *Organoids ; }, abstract = {Many neuromuscular disease entities possess a significant disease burden and therapeutic options remain limited. Innovative human preclinical models may help to uncover relevant disease mechanisms and enhance the translation of therapeutic findings to strengthen neuromuscular disease precision medicine. By concentrating on idiopathic inflammatory muscle disorders, we summarize the recent evolution of the novel in vitro models to study disease mechanisms and therapeutic strategies. A particular focus is laid on the integration and simulation of multicellular interactions of muscle tissue in disease phenotypes in vitro. Finally, the requirements of a neuromuscular disease drug development workflow are discussed with a particular emphasis on cell sources, co-culture systems (including organoids), functionality, and throughput.}, } @article {pmid35396623, year = {2022}, author = {Koide, RT}, title = {On Holobionts, Holospecies, and Holoniches: the Role of Microbial Symbioses in Ecology and Evolution.}, journal = {Microbial ecology}, volume = {}, number = {}, pages = {}, pmid = {35396623}, issn = {1432-184X}, abstract = {My goal in writing this is to increase awareness of the roles played by microbial symbionts in eukaryote ecology and evolution. Most eukaryotes host one or more species of symbiotic microorganisms, including prokaryotes and fungi. Many of these have profound impacts on the biology of their hosts. For example, microbial symbionts may expand the niches of their hosts, cause rapid adaptation of the host to the environment and re-adaptation to novel conditions via symbiont swapping, facilitate speciation, and fundamentally alter our concept of the species. In some cases, microbial symbionts and multicellular eukaryote hosts have a mutual dependency, which has obvious conservation implications. Hopefully, this contribution will stimulate a reevaluation of important ecological and evolutionary concepts including niche, adaptation, the species, speciation, and conservation of multicellular eukaryotes.}, } @article {pmid35359304, year = {2022}, author = {Ramon-Mateu, J and Edgar, A and Mitchell, D and Martindale, MQ}, title = {Studying Ctenophora WBR Using Mnemiopsis leidyi.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2450}, number = {}, pages = {95-119}, pmid = {35359304}, issn = {1940-6029}, mesh = {Animals ; Cell Lineage ; *Ctenophora/genetics ; Genome ; Phylogeny ; }, abstract = {Ctenophores, also known as comb jellies, are a clade of fragile holopelagic, carnivorous marine invertebrates, that represent one of the most ancient extant groups of multicellular animals. Ctenophores show a remarkable ability to regenerate in the adult form, being capable of replacing all body parts (i.e., whole-body regeneration) after loss/amputation. With many favorable experimental features (optical clarity, stereotyped cell lineage, multiple cell types), a full genome sequence available and their early branching phylogenetic position, ctenophores are well placed to provide information about the evolution of regenerative ability throughout the Metazoa. Here, we provide a collection of detailed protocols for use of the lobate ctenophore Mnemiopsis leidyi to study whole-body regeneration, including specimen collection, husbandry, surgical manipulation, and imaging techniques.}, } @article {pmid35358607, year = {2022}, author = {Shapiro, JA}, title = {What we have learned about evolutionary genome change in the past 7 decades.}, journal = {Bio Systems}, volume = {215-216}, number = {}, pages = {104669}, doi = {10.1016/j.biosystems.2022.104669}, pmid = {35358607}, issn = {1872-8324}, mesh = {Animals ; *Biological Evolution ; *DNA Transposable Elements/genetics ; Eukaryota/genetics ; Evolution, Molecular ; Genomics ; Hybridization, Genetic ; }, abstract = {Cytogenetics and genomics have completely transformed our understanding of evolutionary genome change since the early 1950s. The point of this paper is to outline some of the empirical findings responsible for that transformation. The discovery of transposable elements (TEs) in maize by McClintock, and their subsequent rediscovery in all forms of life, tell us that organisms have the inherent capacity to evolve dispersed genomic networks encoding complex cellular and multicellular adaptations. Genomic analysis confirms the role of TEs in wiring novel networks at major evolutionary transitions. TEs and other forms of repetitive DNA are also important contributors to genome regions that serve as transcriptional templates for regulatory and other biologically functional noncoding ncRNAs. The many functions documented for ncRNAs shows the concept of abundant "selfish" or "junk" DNA in complex genomes is mistaken. Natural and artificial speciation by interspecific hybridization demonstrates that TEs and other biochemical systems of genome restructuring are subject to rapid activation and can generate changes throughout the genomes of the novel species that emerge. In addition to TEs and hybrid species, cancer cells have taught us important lessons about chromothripsis, chromoplexy and other forms of non-random multisite genome restructuring. In many of these restructured genomes, alternative end-joining processes display the capacities of eukaryotes to generate novel combinations of templated and untemplated DNA sequences at the sites of break repair. Sequence innovation by alternative end-joining is widespread among eukaryotes from single cells to advanced plants and animals. In sum, the cellular and genomic capacities of eukaryotic cells have proven to be capable of executing rapid macroevolutionary change under a variety of conditions.}, } @article {pmid35353805, year = {2022}, author = {Burnetti, A and Ratcliff, WC}, title = {Experimental evolution is not just for model organisms.}, journal = {PLoS biology}, volume = {20}, number = {3}, pages = {e3001587}, pmid = {35353805}, issn = {1545-7885}, mesh = {Animals ; *Biological Evolution ; }, abstract = {In a new paper published in PLOS Biology, Dudin and colleagues evolve simple multicellularity in Sphaeroforma arctica, a unicellular relative of animals. This work establishes a new and open-ended avenue for examining the evolution of multicellularity in an important but understudied group of organisms.}, } @article {pmid35349792, year = {2022}, author = {Toret, C and Picco, A and Boiero-Sanders, M and Michelot, A and Kaksonen, M}, title = {The cellular slime mold Fonticula alba forms a dynamic, multicellular collective while feeding on bacteria.}, journal = {Current biology : CB}, volume = {32}, number = {9}, pages = {1961-1973.e4}, pmid = {35349792}, issn = {1879-0445}, mesh = {Animals ; Bacteria ; *Dictyosteliida ; Eukaryota ; Fungi ; Phylogeny ; }, abstract = {Multicellularity evolved in fungi and animals, or the opisthokonts, from their common amoeboflagellate ancestor but resulted in strikingly distinct cellular organizations. The origins of this multicellularity divergence are not known. The stark mechanistic differences that underlie the two groups and the lack of information about ancestral cellular organizations limits progress in this field. We discovered a new type of invasive multicellular behavior in Fonticula alba, a unique species in the opisthokont tree, which has a simple, bacteria-feeding sorocarpic amoeba lifestyle. This invasive multicellularity follows germination dependent on the bacterial culture state, after which amoebae coalesce to form dynamic collectives that invade virgin bacterial resources. This bacteria-dependent social behavior emerges from amoeba density and allows for rapid and directed invasion. The motile collectives have animal-like properties but also hyphal-like search and invasive behavior. These surprising findings enrich the diverse multicellularities present within the opisthokont lineage and offer a new perspective on fungal origins.}, } @article {pmid35349578, year = {2022}, author = {Dudin, O and Wielgoss, S and New, AM and Ruiz-Trillo, I}, title = {Regulation of sedimentation rate shapes the evolution of multicellularity in a close unicellular relative of animals.}, journal = {PLoS biology}, volume = {20}, number = {3}, pages = {e3001551}, pmid = {35349578}, issn = {1545-7885}, mesh = {Animals ; Cell Size ; *Cytokinesis ; Phenotype ; }, abstract = {Significant increases in sedimentation rate accompany the evolution of multicellularity. These increases should lead to rapid changes in ecological distribution, thereby affecting the costs and benefits of multicellularity and its likelihood to evolve. However, how genetic and cellular traits control this process, their likelihood of emergence over evolutionary timescales, and the variation in these traits as multicellularity evolves are still poorly understood. Here, using isolates of the ichthyosporean genus Sphaeroforma-close unicellular relatives of animals with brief transient multicellular life stages-we demonstrate that sedimentation rate is a highly variable and evolvable trait affected by at least 2 distinct physical mechanisms. First, we find extensive (>300×) variation in sedimentation rates for different Sphaeroforma species, mainly driven by size and density during the unicellular-to-multicellular life cycle transition. Second, using experimental evolution with sedimentation rate as a focal trait, we readily obtained, for the first time, fast settling and multicellular Sphaeroforma arctica isolates. Quantitative microscopy showed that increased sedimentation rates most often arose by incomplete cellular separation after cell division, leading to clonal "clumping" multicellular variants with increased size and density. Strikingly, density increases also arose by an acceleration of the nuclear doubling time relative to cell size. Similar size- and density-affecting phenotypes were observed in 4 additional species from the Sphaeroforma genus, suggesting that variation in these traits might be widespread in the marine habitat. By resequencing evolved isolates to high genomic coverage, we identified mutations in regulators of cytokinesis, plasma membrane remodeling, and chromatin condensation that may contribute to both clump formation and the increase in the nuclear number-to-volume ratio. Taken together, this study illustrates how extensive cellular control of density and size drive sedimentation rate variation, likely shaping the onset and further evolution of multicellularity.}, } @article {pmid35337467, year = {2022}, author = {Booth, DS and King, N}, title = {The history of Salpingoeca rosetta as a model for reconstructing animal origins.}, journal = {Current topics in developmental biology}, volume = {147}, number = {}, pages = {73-91}, doi = {10.1016/bs.ctdb.2022.01.001}, pmid = {35337467}, issn = {1557-8933}, mesh = {Animals ; *Choanoflagellata/genetics ; Developmental Biology ; }, abstract = {Choanoflagellates, the closest living relatives of animals, have the potential to reveal the genetic and cell biological foundations of complex multicellular development in animals. Here we describe the history of research on the choanoflagellate Salpingoeca rosetta. From its original isolation in 2000 to the establishment of CRISPR-mediated genome editing in 2020, S. rosetta provides an instructive case study in the establishment of a new model organism.}, } @article {pmid35318703, year = {2022}, author = {Hammond, M and Dorrell, RG and Speijer, D and Lukeš, J}, title = {Eukaryotic cellular intricacies shape mitochondrial proteomic complexity.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {44}, number = {5}, pages = {e2100258}, doi = {10.1002/bies.202100258}, pmid = {35318703}, issn = {1521-1878}, mesh = {Biological Evolution ; Eukaryota/physiology ; *Eukaryotic Cells/metabolism ; Mitochondria/metabolism ; Organelles/metabolism ; Phylogeny ; *Proteomics ; }, abstract = {Mitochondria have been fundamental to the eco-physiological success of eukaryotes since the last eukaryotic common ancestor (LECA). They contribute essential functions to eukaryotic cells, above and beyond classical respiration. Mitochondria interact with, and complement, metabolic pathways occurring in other organelles, notably diversifying the chloroplast metabolism of photosynthetic organisms. Here, we integrate existing literature to investigate how mitochondrial metabolism varies across the landscape of eukaryotic evolution. We illustrate the mitochondrial remodelling and proteomic changes undergone in conjunction with major evolutionary transitions. We explore how the mitochondrial complexity of the LECA has been remodelled in specific groups to support subsequent evolutionary transitions, such as the acquisition of chloroplasts in photosynthetic species and the emergence of multicellularity. We highlight the versatile and crucial roles played by mitochondria during eukaryotic evolution, extending from its huge contribution to the development of the LECA itself to the dynamic evolution of individual eukaryote groups, reflecting both their current ecologies and evolutionary histories.}, } @article {pmid35317961, year = {2023}, author = {Bogaert, KA and Zakka, EE and Coelho, SM and De Clerck, O}, title = {Polarization of brown algal zygotes.}, journal = {Seminars in cell & developmental biology}, volume = {134}, number = {}, pages = {90-102}, doi = {10.1016/j.semcdb.2022.03.008}, pmid = {35317961}, issn = {1096-3634}, mesh = {Animals ; Zygote ; *Arabidopsis ; *Phaeophyta/genetics/metabolism ; Cell Polarity ; Cell Division ; Plants ; }, abstract = {Brown algae are a group of multicellular, heterokont algae that have convergently evolved developmental complexity that rivals that of embryophytes, animals or fungi. Early in development, brown algal zygotes establish a basal and an apical pole, which will become respectively the basal system (holdfast) and the apical system (thallus) of the adult alga. Brown algae are interesting models for understanding the establishment of cell polarity in a broad evolutionary context, because they exhibit a large diversity of life cycles, reproductive strategies and, importantly, their zygotes are produced in large quantities free of parental tissue, with symmetry breaking and asymmetric division taking place in a highly synchronous manner. This review describes the current knowledge about the establishment of the apical-basal axis in the model brown seaweeds Ectocarpus, Dictyota, Fucus and Saccharina, highlighting the advantages and specific interests of each system. Ectocarpus is a genetic model system that allows access to the molecular basis of early development and life-cycle control over apical-basal polarity. The oogamous brown alga Fucus, together with emerging comparative models Dictyota and Saccharina, emphasize the diversity of strategies of symmetry breaking in determining a cell polarity vector in brown algae. A comparison with symmetry-breaking mechanisms in land plants, animals and fungi, reveals that the one-step zygote polarisation of Fucus compares well to Saccharomyces budding and Arabidopsis stomata development, while the two-phased symmetry breaking in the Dictyota zygote compares to Schizosaccharomyces fission, the Caenorhabditis anterior-posterior zygote polarisation and Arabidopsis prolate pollen polarisation. The apical-basal patterning in Saccharina zygotes on the other hand, may be seen as analogous to that of land plants. Overall, brown algae have the potential to bring exciting new information on how a single cell gives rise to an entire complex body plan.}, } @article {pmid35311270, year = {2022}, author = {Chen, C and Wang, P and Chen, H and Wang, X and Halgamuge, MN and Chen, C and Song, T}, title = {Smart Magnetotactic Bacteria Enable the Inhibition of Neuroblastoma under an Alternating Magnetic Field.}, journal = {ACS applied materials & interfaces}, volume = {14}, number = {12}, pages = {14049-14058}, doi = {10.1021/acsami.1c24154}, pmid = {35311270}, issn = {1944-8252}, mesh = {Animals ; *Hyperthermia, Induced ; Magnetic Fields ; *Magnetosomes/metabolism ; Mice ; Mice, Nude ; *Neuroblastoma/metabolism/therapy ; }, abstract = {Magnetotactic bacteria are ubiquitous microorganisms in nature that synthesize intracellular magnetic nanoparticles called magnetosomes in a gene-controlled way and arrange them in chains. From in vitro to in vivo, we demonstrate that the intact body of Magnetospirillum magneticum AMB-1 has potential as a natural magnetic hyperthermia material for cancer therapy. Compared to chains of magnetosomes and individual magnetosomes, the entire AMB-1 cell exhibits superior heating capability under an alternating magnetic field. When incubating with tumor cells, the intact AMB-1 cells disperse better than the other two types of magnetosomes, decreasing cellular viability under the control of an alternating magnetic field. Furthermore, in vivo experiments in nude mice with neuroblastoma found that intact AMB-1 cells had the best antitumor activity with magnetic hyperthermia therapy compared to other treatment groups. These findings suggest that the intact body of magnetotactic bacteria has enormous promise as a natural material for tumor magnetic hyperthermia. In biomedical applications, intact and living magnetotactic bacteria play an increasingly essential function as a targeting robot due to their magnetotaxis.}, } @article {pmid35295942, year = {2022}, author = {Jiménez-Marín, B and Olson, BJSC}, title = {The Curious Case of Multicellularity in the Volvocine Algae.}, journal = {Frontiers in genetics}, volume = {13}, number = {}, pages = {787665}, pmid = {35295942}, issn = {1664-8021}, abstract = {The evolution of multicellularity is a major evolutionary transition that underlies the radiation of many species in all domains of life, especially in eukaryotes. The volvocine green algae are an unconventional model system that holds great promise in the field given its genetic tractability, late transition to multicellularity, and phenotypic diversity. Multiple efforts at linking multicellularity-related developmental landmarks to key molecular changes, especially at the genome level, have provided key insights into the molecular innovations or lack thereof that underlie multicellularity. Twelve developmental changes have been proposed to explain the evolution of complex differentiated multicellularity in the volvocine algae. Co-option of key genes, such as cell cycle and developmental regulators has been observed, but with few exceptions, known co-option events do not seem to coincide with most developmental features observed in multicellular volvocines. The apparent lack of "master multicellularity genes" combined with no apparent correlation between gene gains for developmental processes suggest the possibility that many multicellular traits might be the product gene-regulatory and functional innovations; in other words, multicellularity can arise from shared genomic repertoires that undergo regulatory and functional overhauls.}, } @article {pmid35251134, year = {2022}, author = {Palazzo, AF and Kejiou, NS}, title = {Non-Darwinian Molecular Biology.}, journal = {Frontiers in genetics}, volume = {13}, number = {}, pages = {831068}, pmid = {35251134}, issn = {1664-8021}, abstract = {With the discovery of the double helical structure of DNA, a shift occurred in how biologists investigated questions surrounding cellular processes, such as protein synthesis. Instead of viewing biological activity through the lens of chemical reactions, this new field used biological information to gain a new profound view of how biological systems work. Molecular biologists asked new types of questions that would have been inconceivable to the older generation of researchers, such as how cellular machineries convert inherited biological information into functional molecules like proteins. This new focus on biological information also gave molecular biologists a way to link their findings to concepts developed by genetics and the modern synthesis. However, by the late 1960s this all changed. Elevated rates of mutation, unsustainable genetic loads, and high levels of variation in populations, challenged Darwinian evolution, a central tenant of the modern synthesis, where adaptation was the main driver of evolutionary change. Building on these findings, Motoo Kimura advanced the neutral theory of molecular evolution, which advocates that selection in multicellular eukaryotes is weak and that most genomic changes are neutral and due to random drift. This was further elaborated by Jack King and Thomas Jukes, in their paper "Non-Darwinian Evolution", where they pointed out that the observed changes seen in proteins and the types of polymorphisms observed in populations only become understandable when we take into account biochemistry and Kimura's new theory. Fifty years later, most molecular biologists remain unaware of these fundamental advances. Their adaptionist viewpoint fails to explain data collected from new powerful technologies which can detect exceedingly rare biochemical events. For example, high throughput sequencing routinely detects RNA transcripts being produced from almost the entire genome yet are present less than one copy per thousand cells and appear to lack any function. Molecular biologists must now reincorporate ideas from classical biochemistry and absorb modern concepts from molecular evolution, to craft a new lens through which they can evaluate the functionality of transcriptional units, and make sense of our messy, intricate, and complicated genome.}, } @article {pmid35246710, year = {2022}, author = {Frenkel-Pinter, M and Petrov, AS and Matange, K and Travisano, M and Glass, JB and Williams, LD}, title = {Adaptation and Exaptation: From Small Molecules to Feathers.}, journal = {Journal of molecular evolution}, volume = {90}, number = {2}, pages = {166-175}, pmid = {35246710}, issn = {1432-1432}, support = {80NSSC18K1139/ImNASA/Intramural NASA/United States ; }, mesh = {Acclimatization ; *Adaptation, Physiological/genetics ; Animals ; Biological Evolution ; *Feathers ; }, abstract = {Evolution works by adaptation and exaptation. At an organismal level, exaptation and adaptation are seen in the formation of organelles and the advent of multicellularity. At the sub-organismal level, molecular systems such as proteins and RNAs readily undergo adaptation and exaptation. Here we suggest that the concepts of adaptation and exaptation are universal, synergistic, and recursive and apply to small molecules such as metabolites, cofactors, and the building blocks of extant polymers. For example, adenosine has been extensively adapted and exapted throughout biological evolution. Chemical variants of adenosine that are products of adaptation include 2' deoxyadenosine in DNA and a wide array of modified forms in mRNAs, tRNAs, rRNAs, and viral RNAs. Adenosine and its variants have been extensively exapted for various functions, including informational polymers (RNA, DNA), energy storage (ATP), metabolism (e.g., coenzyme A), and signaling (cyclic AMP). According to Gould, Vrba, and Darwin, exaptation imposes a general constraint on interpretation of history and origins; because of exaptation, extant function should not be used to explain evolutionary history. While this notion is accepted in evolutionary biology, it can also guide the study of the chemical origins of life. We propose that (i) evolutionary theory is broadly applicable from the dawn of life to the present time from molecules to organisms, (ii) exaptation and adaptation were important and simultaneous processes, and (iii) robust origin of life models can be constructed without conflating extant utility with historical basis of origins.}, } @article {pmid35235070, year = {2022}, author = {Kwantes, M and Wichard, T}, title = {The APAF1_C/WD40 repeat domain-encoding gene from the sea lettuce Ulva mutabilis sheds light on the evolution of NB-ARC domain-containing proteins in green plants.}, journal = {Planta}, volume = {255}, number = {4}, pages = {76}, pmid = {35235070}, issn = {1432-2048}, mesh = {Ecosystem ; Phylogeny ; Plant Proteins/metabolism ; Proteins/genetics ; *Ulva/genetics ; WD40 Repeats ; }, abstract = {We advance Ulva's genetic tractability and highlight its value as a model organism by characterizing its APAF1_C/WD40 domain-encoding gene, which belongs to a family that bears homology to R genes. The multicellular chlorophyte alga Ulva mutabilis (Ulvophyceae, Ulvales) is native to coastal ecosystems worldwide and attracts both high socio-economic and scientific interest. To further understand the genetic mechanisms that guide its biology, we present a protocol, based on adapter ligation-mediated PCR, for retrieving flanking sequences in U. mutabilis vector-insertion mutants. In the created insertional library, we identified a null mutant with an insertion in an apoptotic protease activating factor 1 helical domain (APAF1_C)/WD40 repeat domain-encoding gene. Protein domain architecture analysis combined with phylogenetic analysis revealed that this gene is a member of a subfamily that arose early in the evolution of green plants (Viridiplantae) through the acquisition of a gene that also encoded N-terminal nucleotide-binding adaptor shared by APAF-1, certain R-gene products and CED-4 (NB-ARC) and winged helix-like (WH-like) DNA-binding domains. Although phenotypic analysis revealed no mutant phenotype, gene expression levels in control plants correlated to the presence of bacterial symbionts, which U. mutabilis requires for proper morphogenesis. In addition, our analysis led to the discovery of a putative Ulva nucleotide-binding site and leucine-rich repeat (NBS-LRR) Resistance protein (R-protein), and we discuss how the emergence of these R proteins in green plants may be linked to the evolution of the APAF1_C/WD40 protein subfamily.}, } @article {pmid35218347, year = {2022}, author = {Spang, A and Mahendrarajah, TA and Offre, P and Stairs, CW}, title = {Evolving Perspective on the Origin and Diversification of Cellular Life and the Virosphere.}, journal = {Genome biology and evolution}, volume = {14}, number = {6}, pages = {}, pmid = {35218347}, issn = {1759-6653}, mesh = {*Archaea ; Biological Evolution ; Eukaryota ; Phylogeny ; *Viruses/genetics ; }, abstract = {The tree of life (TOL) is a powerful framework to depict the evolutionary history of cellular organisms through time, from our microbial origins to the diversification of multicellular eukaryotes that shape the visible biosphere today. During the past decades, our perception of the TOL has fundamentally changed, in part, due to profound methodological advances, which allowed a more objective approach to studying organismal and viral diversity and led to the discovery of major new branches in the TOL as well as viral lineages. Phylogenetic and comparative genomics analyses of these data have, among others, revolutionized our understanding of the deep roots and diversity of microbial life, the origin of the eukaryotic cell, eukaryotic diversity, as well as the origin, and diversification of viruses. In this review, we provide an overview of some of the recent discoveries on the evolutionary history of cellular organisms and their viruses and discuss a variety of complementary techniques that we consider crucial for making further progress in our understanding of the TOL and its interconnection with the virosphere.}, } @article {pmid35205423, year = {2022}, author = {Alfieri, JM and Wang, G and Jonika, MM and Gill, CA and Blackmon, H and Athrey, GN}, title = {A Primer for Single-Cell Sequencing in Non-Model Organisms.}, journal = {Genes}, volume = {13}, number = {2}, pages = {}, pmid = {35205423}, issn = {2073-4425}, support = {R35 GM138098/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Genotype ; *Phenotype ; }, abstract = {Single-cell sequencing technologies have led to a revolution in our knowledge of the diversity of cell types, connections between biological levels of organization, and relationships between genotype and phenotype. These advances have mainly come from using model organisms; however, using single-cell sequencing in non-model organisms could enable investigations of questions inaccessible with typical model organisms. This primer describes a general workflow for single-cell sequencing studies and considerations for using non-model organisms (limited to multicellular animals). Importantly, single-cell sequencing, when further applied in non-model organisms, will allow for a deeper understanding of the mechanisms between genotype and phenotype and the basis for biological variation.}, } @article {pmid35194081, year = {2022}, author = {Lin, HK and Cheng, JH and Wu, CC and Hsieh, FS and Dunlap, C and Chen, SH}, title = {Functional buffering via cell-specific gene expression promotes tissue homeostasis and cancer robustness.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {2974}, pmid = {35194081}, issn = {2045-2322}, mesh = {*Databases, Nucleic Acid ; *Gene Expression Regulation, Neoplastic ; *Homeostasis ; Humans ; *Neoplasms/genetics/metabolism ; Organ Specificity ; }, abstract = {Functional buffering that ensures biological robustness is critical for maintaining tissue homeostasis, organismal survival, and evolution of novelty. However, the mechanism underlying functional buffering, particularly in multicellular organisms, remains largely elusive. Here, we proposed that functional buffering can be mediated via expression of buffering genes in specific cells and tissues, by which we named Cell-specific Expression-BUffering (CEBU). We developed an inference index (C-score) for CEBU by computing C-scores across 684 human cell lines using genome-wide CRISPR screens and transcriptomic RNA-seq. We report that C-score-identified putative buffering gene pairs are enriched for members of the same duplicated gene family, pathway, and protein complex. Furthermore, CEBU is especially prevalent in tissues of low regenerative capacity (e.g., bone and neuronal tissues) and is weakest in highly regenerative blood cells, linking functional buffering to tissue regeneration. Clinically, the buffering capacity enabled by CEBU can help predict patient survival for multiple cancers. Our results suggest CEBU as a potential buffering mechanism contributing to tissue homeostasis and cancer robustness in humans.}, } @article {pmid35189700, year = {2022}, author = {Simon-Soro, A and Ren, Z and Krom, BP and Hoogenkamp, MA and Cabello-Yeves, PJ and Daniel, SG and Bittinger, K and Tomas, I and Koo, H and Mira, A}, title = {Polymicrobial Aggregates in Human Saliva Build the Oral Biofilm.}, journal = {mBio}, volume = {13}, number = {1}, pages = {e0013122}, pmid = {35189700}, issn = {2150-7511}, support = {R01 DE025220/DE/NIDCR NIH HHS/United States ; }, mesh = {Bacteria ; Biofilms ; *Ecosystem ; Humans ; Phylogeny ; *Saliva/microbiology ; }, abstract = {Biofilm community development has been established as a sequential process starting from the attachment of single cells on a surface. However, microorganisms are often found as aggregates in the environment and in biological fluids. Here, we conduct a comprehensive analysis of the native structure and composition of aggregated microbial assemblages in human saliva and investigate their spatiotemporal attachment and biofilm community development. Using multiscale imaging, cell sorting, and computational approaches combined with sequencing analysis, a diverse mixture of aggregates varying in size, structure, and microbial composition, including bacteria associated with host epithelial cells, can be found in saliva in addition to a few single-cell forms. Phylogenetic analysis reveals a mixture of complex consortia of aerobes and anaerobes in which bacteria traditionally considered early and late colonizers are found mixed together. When individually tracked during colonization and biofilm initiation, aggregates rapidly proliferate and expand tridimensionally, modulating population growth, spatial organization, and community scaffolding. In contrast, most single cells remain static or are incorporated by actively growing aggregates. These results suggest an alternative biofilm development process whereby aggregates containing different species or associated with human cells collectively adhere to the surface as "growth nuclei" to build the biofilm and shape polymicrobial communities at various spatial and taxonomic scales. IMPORTANCE Microbes in biological fluids can be found as aggregates. How these multicellular structures bind to surfaces and initiate the biofilm life cycle remains understudied. Here, we investigate the structural organization of microbial aggregates in human saliva and their role in biofilm formation. We found diverse mixtures of aggregates with different sizes, structures, and compositions in addition to free-living cells. When individually tracked during binding and growth on tooth-like surfaces, most aggregates developed into structured biofilm communities, whereas most single cells remained static or were engulfed by the growing aggregates. Our results reveal that preformed microbial consortia adhere as "buds of growth," governing biofilm initiation without specific taxonomic order or cell-by-cell succession, which provide new insights into spatial and population heterogeneity development in complex ecosystems.}, } @article {pmid35188101, year = {2022}, author = {Day, TC and Höhn, SS and Zamani-Dahaj, SA and Yanni, D and Burnetti, A and Pentz, J and Honerkamp-Smith, AR and Wioland, H and Sleath, HR and Ratcliff, WC and Goldstein, RE and Yunker, PJ}, title = {Cellular organization in lab-evolved and extant multicellular species obeys a maximum entropy law.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {35188101}, issn = {2050-084X}, support = {/WT_/Wellcome Trust/United Kingdom ; 207510/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; R35 GM138030/GM/NIGMS NIH HHS/United States ; R35 GM138354/GM/NIGMS NIH HHS/United States ; }, mesh = {Cell Size ; *Directed Molecular Evolution ; Phylogeny ; Volvox/cytology/*genetics/physiology ; Yeasts/cytology/*genetics/physiology ; }, abstract = {The prevalence of multicellular organisms is due in part to their ability to form complex structures. How cells pack in these structures is a fundamental biophysical issue, underlying their functional properties. However, much remains unknown about how cell packing geometries arise, and how they are affected by random noise during growth - especially absent developmental programs. Here, we quantify the statistics of cellular neighborhoods of two different multicellular eukaryotes: lab-evolved 'snowflake' yeast and the green alga Volvox carteri. We find that despite large differences in cellular organization, the free space associated with individual cells in both organisms closely fits a modified gamma distribution, consistent with maximum entropy predictions originally developed for granular materials. This 'entropic' cellular packing ensures a degree of predictability despite noise, facilitating parent-offspring fidelity even in the absence of developmental regulation. Together with simulations of diverse growth morphologies, these results suggest that gamma-distributed cell neighborhood sizes are a general feature of multicellularity, arising from conserved statistics of cellular packing.}, } @article {pmid35186015, year = {2021}, author = {Zeng, Q and Liu, H and Chu, X and Niu, Y and Wang, C and Markov, GV and Teng, L}, title = {Independent Evolution of the MYB Family in Brown Algae.}, journal = {Frontiers in genetics}, volume = {12}, number = {}, pages = {811993}, pmid = {35186015}, issn = {1664-8021}, abstract = {Myeloblastosis (MYB) proteins represent one of the largest families of eukaryotic transcription factors and regulate important processes in growth and development. Studies on MYBs have mainly focused on animals and plants; however, comprehensive analysis across other supergroups such as SAR (stramenopiles, alveolates, and rhizarians) is lacking. This study characterized the structure, evolution, and expression of MYBs in four brown algae, which comprise the biggest multicellular lineage of SAR. Subfamily 1R-MYB comprised heterogeneous proteins, with fewer conserved motifs found outside the MYB domain. Unlike the SHAQKY subgroup of plant 1R-MYB, THAQKY comprised the largest subgroup of brown algal 1R-MYBs. Unlike the expansion of 2R-MYBs in plants, brown algae harbored more 3R-MYBs than 2R-MYBs. At least ten 2R-MYBs, fifteen 3R-MYBs, and one 6R-MYB orthologs existed in the common ancestor of brown algae. Phylogenetic analysis showed that brown algal MYBs had ancient origins and a diverged evolution. They showed strong affinity with stramenopile species, while not with red algae, green algae, or animals, suggesting that brown algal MYBs did not come from the secondary endosymbiosis of red and green plastids. Sequence comparison among all repeats of the three types of MYB subfamilies revealed that the repeat of 1R-MYBs showed higher sequence identity with the R3 of 2R-MYBs and 3R-MYBs, which supports the idea that 1R-MYB was derived from loss of the first and second repeats of the ancestor MYB. Compared with other species of SAR, brown algal MYB proteins exhibited a higher proportion of intrinsic disordered regions, which might contribute to multicellular evolution. Expression analysis showed that many MYB genes are responsive to different stress conditions and developmental stages. The evolution and expression analyses provided a comprehensive analysis of the phylogeny and functions of MYBs in brown algae.}, } @article {pmid35167804, year = {2022}, author = {Davis, JR and Ainslie, AP and Williamson, JJ and Ferreira, A and Torres-Sánchez, A and Hoppe, A and Mangione, F and Smith, MB and Martin-Blanco, E and Salbreux, G and Tapon, N}, title = {ECM degradation in the Drosophila abdominal epidermis initiates tissue growth that ceases with rapid cell-cycle exit.}, journal = {Current biology : CB}, volume = {32}, number = {6}, pages = {1285-1300.e4}, pmid = {35167804}, issn = {1879-0445}, support = {FC001175/MRC_/Medical Research Council/United Kingdom ; FC001317/WT_/Wellcome Trust/United Kingdom ; 107885/Z/15/Z/WT_/Wellcome Trust/United Kingdom ; FC001175/WT_/Wellcome Trust/United Kingdom ; FC001175/ARC_/Arthritis Research UK/United Kingdom ; FC001317/ARC_/Arthritis Research UK/United Kingdom ; FC001317/CRUK_/Cancer Research UK/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; FC001317/MRC_/Medical Research Council/United Kingdom ; FC001175/CRUK_/Cancer Research UK/United Kingdom ; 201358/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Cell Cycle ; Cell Division ; *Drosophila ; *Epidermal Cells ; Epidermis ; Mice ; }, abstract = {During development, multicellular organisms undergo stereotypical patterns of tissue growth in space and time. How developmental growth is orchestrated remains unclear, largely due to the difficulty of observing and quantitating this process in a living organism. Drosophila histoblast nests are small clusters of progenitor epithelial cells that undergo extensive growth to give rise to the adult abdominal epidermis and are amenable to live imaging. Our quantitative analysis of histoblast proliferation and tissue mechanics reveals that tissue growth is driven by cell divisions initiated through basal extracellular matrix degradation by matrix metalloproteases secreted by the neighboring larval epidermal cells. Laser ablations and computational simulations show that tissue mechanical tension does not decrease as the histoblasts fill the abdominal epidermal surface. During tissue growth, the histoblasts display oscillatory cell division rates until growth termination occurs through the rapid emergence of G0/G1 arrested cells, rather than a gradual increase in cell-cycle time as observed in other systems such as the Drosophila wing and mouse postnatal epidermis. Different developing tissues can therefore achieve their final size using distinct growth termination strategies. Thus, adult abdominal epidermal development is characterized by changes in the tissue microenvironment and a rapid exit from the cell cycle.}, } @article {pmid35159213, year = {2022}, author = {Ribba, AS and Fraboulet, S and Sadoul, K and Lafanechère, L}, title = {The Role of LIM Kinases during Development: A Lens to Get a Glimpse of Their Implication in Pathologies.}, journal = {Cells}, volume = {11}, number = {3}, pages = {}, pmid = {35159213}, issn = {2073-4409}, mesh = {Actin Depolymerizing Factors/metabolism ; Animals ; *Lim Kinases/metabolism ; Phosphorylation ; Phylogeny ; *Protein Kinases/metabolism ; }, abstract = {The organization of cell populations within animal tissues is essential for the morphogenesis of organs during development. Cells recognize three-dimensional positions with respect to the whole organism and regulate their cell shape, motility, migration, polarization, growth, differentiation, gene expression and cell death according to extracellular signals. Remodeling of the actin filaments is essential to achieve these cell morphological changes. Cofilin is an important binding protein for these filaments; it increases their elasticity in terms of flexion and torsion and also severs them. The activity of cofilin is spatiotemporally inhibited via phosphorylation by the LIM domain kinases 1 and 2 (LIMK1 and LIMK2). Phylogenetic analysis indicates that the phospho-regulation of cofilin has evolved as a mechanism controlling the reorganization of the actin cytoskeleton during complex multicellular processes, such as those that occur during embryogenesis. In this context, the main objective of this review is to provide an update of the respective role of each of the LIM kinases during embryonic development.}, } @article {pmid35154170, year = {2021}, author = {Žárský, J and Žárský, V and Hanáček, M and Žárský, V}, title = {Cryogenian Glacial Habitats as a Plant Terrestrialisation Cradle - The Origin of the Anydrophytes and Zygnematophyceae Split.}, journal = {Frontiers in plant science}, volume = {12}, number = {}, pages = {735020}, pmid = {35154170}, issn = {1664-462X}, abstract = {For tens of millions of years (Ma), the terrestrial habitats of Snowball Earth during the Cryogenian period (between 720 and 635 Ma before present-Neoproterozoic Era) were possibly dominated by global snow and ice cover up to the equatorial sublimative desert. The most recent time-calibrated phylogenies calibrated not only on plants but on a comprehensive set of eukaryotes indicate that within the Streptophyta, multicellular charophytes (Phragmoplastophyta) evolved in the Mesoproterozoic to the early Neoproterozoic. At the same time, Cryogenian is the time of the likely origin of the common ancestor of Zygnematophyceae and Embryophyta and later, also of the Zygnematophyceae-Embryophyta split. This common ancestor is proposed to be called Anydrophyta; here, we use anydrophytes. Based on the combination of published phylogenomic studies and estimated diversification time comparisons, we deem it highly likely that anydrophytes evolved in response to Cryogenian cooling. Also, later in the Cryogenian, secondary simplification of multicellular anydrophytes and loss of flagella resulted in Zygnematophyceae diversification as an adaptation to the extended cold glacial environment. We propose that the Marinoan geochemically documented expansion of first terrestrial flora has been represented not only by Chlorophyta but also by Streptophyta, including the anydrophytes, and later by Zygnematophyceae, thriving on glacial surfaces until today. It is possible that multicellular early Embryophyta survived in less abundant (possibly relatively warmer) refugia, relying more on mineral substrates, allowing the retention of flagella-based sexuality. The loss of flagella and sexual reproduction by conjugation evolved in Zygnematophyceae and zygomycetous fungi during the Cryogenian in a remarkably convergent way. Thus, we support the concept that the important basal cellular adaptations to terrestrial environments were exapted in streptophyte algae for terrestrialization and propose that this was stimulated by the adaptation to glacial habitats dominating the Cryogenian Snowball Earth. Including the glacial lifestyle when considering the rise of land plants increases the parsimony of connecting different ecological, phylogenetic, and physiological puzzles of the journey from aquatic algae to terrestrial floras.}, } @article {pmid35143488, year = {2022}, author = {Yaguchi, S and Taniguchi, Y and Suzuki, H and Kamata, M and Yaguchi, J}, title = {Planktonic sea urchin larvae change their swimming direction in response to strong photoirradiation.}, journal = {PLoS genetics}, volume = {18}, number = {2}, pages = {e1010033}, pmid = {35143488}, issn = {1553-7404}, mesh = {Animals ; Cilia/metabolism ; Larva/metabolism ; Light ; Locomotion/physiology ; Movement/*physiology ; Muscles/physiology ; Opsins/genetics/metabolism ; Photoreceptor Cells/*metabolism ; Plankton ; Sea Urchins/*metabolism ; }, abstract = {To survive, organisms need to precisely respond to various environmental factors, such as light and gravity. Among these, light is so important for most life on Earth that light-response systems have become extraordinarily developed during evolution, especially in multicellular animals. A combination of photoreceptors, nervous system components, and effectors allows these animals to respond to light stimuli. In most macroscopic animals, muscles function as effectors responding to light, and in some microscopic aquatic animals, cilia play a role. It is likely that the cilia-based response was the first to develop and that it has been substituted by the muscle-based response along with increases in body size. However, although the function of muscle appears prominent, it is poorly understood whether ciliary responses to light are present and/or functional, especially in deuterostomes, because it is possible that these responses are too subtle to be observed, unlike muscle responses. Here, we show that planktonic sea urchin larvae reverse their swimming direction due to the inhibitory effect of light on the cholinergic neuron signaling>forward swimming pathway. We found that strong photoirradiation of larvae that stay on the surface of seawater immediately drives the larvae away from the surface due to backward swimming. When Opsin2, which is expressed in mesenchymal cells in larval arms, is knocked down, the larvae do not show backward swimming under photoirradiation. Although Opsin2-expressing cells are not neuronal cells, immunohistochemical analysis revealed that they directly attach to cholinergic neurons, which are thought to regulate forward swimming. These data indicate that light, through Opsin2, inhibits the activity of cholinergic signaling, which normally promotes larval forward swimming, and that the light-dependent ciliary response is present in deuterostomes. These findings shed light on how light-responsive tissues/organelles have been conserved and diversified during evolution.}, } @article {pmid35135345, year = {2022}, author = {La Richelière, F and Muñoz, G and Guénard, B and Dunn, RR and Economo, EP and Powell, S and Sanders, NJ and Weiser, MD and Abouheif, E and Lessard, JP}, title = {Warm and arid regions of the world are hotspots of superorganism complexity.}, journal = {Proceedings. Biological sciences}, volume = {289}, number = {1968}, pages = {20211899}, pmid = {35135345}, issn = {1471-2954}, mesh = {Animals ; *Ants/genetics ; Desert Climate ; Neurons ; Phenotype ; }, abstract = {Biologists have long been fascinated by the processes that give rise to phenotypic complexity of organisms, yet whether there exist geographical hotspots of phenotypic complexity remains poorly explored. Phenotypic complexity can be readily observed in ant colonies, which are superorganisms with morphologically differentiated queen and worker castes analogous to the germline and soma of multicellular organisms. Several ant species have evolved 'worker polymorphism', where workers in a single colony show quantifiable differences in size and head-to-body scaling. Here, we use 256 754 occurrence points from 8990 ant species to investigate the geography of worker polymorphism. We show that arid regions of the world are the hotspots of superorganism complexity. Tropical savannahs and deserts, which are typically species-poor relative to tropical or even temperate forests, harbour the highest densities of polymorphic ants. We discuss the possible adaptive advantages that worker polymorphism provides in arid environments. Our work may provide a window into the environmental conditions that promote the emergence of highly complex phenotypes.}, } @article {pmid35053310, year = {2022}, author = {Shevyrev, D and Tereshchenko, V and Kozlov, V and Sennikov, S}, title = {Phylogeny, Structure, Functions, and Role of AIRE in the Formation of T-Cell Subsets.}, journal = {Cells}, volume = {11}, number = {2}, pages = {}, pmid = {35053310}, issn = {2073-4409}, mesh = {Evolution, Molecular ; Humans ; Peptides/metabolism ; *Phylogeny ; T-Lymphocyte Subsets/*metabolism ; Transcription Factors/*chemistry/classification/*metabolism ; Transcriptome/genetics ; }, abstract = {It is well known that the most important feature of adaptive immunity is the specificity that provides highly precise recognition of the self, altered-self, and non-self. Due to the high specificity of antigen recognition, the adaptive immune system participates in the maintenance of genetic homeostasis, supports multicellularity, and protects an organism from different pathogens at a qualitatively different level than innate immunity. This seemingly simple property is based on millions of years of evolution that led to the formation of diversification mechanisms of antigen-recognizing receptors and later to the emergence of a system of presentation of the self and non-self antigens. The latter could have a crucial significance because the presentation of nearly complete diversity of auto-antigens in the thymus allows for the "calibration" of the forming repertoires of T-cells for the recognition of self, altered-self, and non-self antigens that are presented on the periphery. The central role in this process belongs to promiscuous gene expression by the thymic epithelial cells that express nearly the whole spectrum of proteins encoded in the genome, meanwhile maintaining their cellular identity. This complex mechanism requires strict control that is executed by several transcription factors. One of the most important of them is AIRE. This noncanonical transcription factor not only regulates the processes of differentiation and expression of peripheral tissue-specific antigens in the thymic medullar epithelial cells but also controls intercellular interactions in the thymus. Besides, it participates in an increase in the diversity and transfer of presented antigens and thus influences the formation of repertoires of maturing thymocytes. Due to these complex effects, AIRE is also called a transcriptional regulator. In this review, we briefly described the history of AIRE discovery, its structure, functions, and role in the formation of antigen-recognizing receptor repertoires, along with other transcription factors. We focused on the phylogenetic prerequisites for the development of modern adaptive immunity and emphasized the importance of the antigen presentation system.}, } @article {pmid35051729, year = {2022}, author = {Masqué-Soler, N and Gehrung, M and Kosmidou, C and Li, X and Diwan, I and Rafferty, C and Atabakhsh, E and Markowetz, F and Fitzgerald, RC}, title = {Computational pathology aids derivation of microRNA biomarker signals from Cytosponge samples.}, journal = {EBioMedicine}, volume = {76}, number = {}, pages = {103814}, pmid = {35051729}, issn = {2352-3964}, mesh = {Artificial Intelligence ; *Barrett Esophagus/genetics ; Biomarkers/metabolism ; Cross-Sectional Studies ; *Esophageal Neoplasms/diagnosis/genetics/pathology ; Humans ; *MicroRNAs/genetics ; }, abstract = {BACKGROUND: Non-endoscopic cell collection devices combined with biomarkers can detect Barrett's intestinal metaplasia and early oesophageal cancer. However, assays performed on multi-cellular samples lose information about the cell source of the biomarker signal. This cross-sectional study examines whether a bespoke artificial intelligence-based computational pathology tool could ascertain the cellular origin of microRNA biomarkers, to inform interpretation of the disease pathology, and confirm biomarker validity.

METHODS: The microRNA expression profiles of 110 targets were assessed with a custom multiplexed panel in a cohort of 117 individuals with reflux that took a Cytosponge test. A computational pathology tool quantified the amount of columnar epithelium present in pathology slides, and results were correlated with microRNA signals. An independent cohort of 139 Cytosponges, each from an individual patient, was used to validate the findings via qPCR.

FINDINGS: Seventeen microRNAs are upregulated in BE compared to healthy squamous epithelia, of which 13 remain upregulated in dysplasia. A pathway enrichment analysis confirmed association to neoplastic and cell cycle regulation processes. Ten microRNAs positively correlated with columnar epithelium content, with miRNA-192-5p and -194-5p accurately detecting the presence of gastric cells (AUC 0.97 and 0.95). In contrast, miR-196a-5p is confirmed as a specific BE marker.

INTERPRETATION: Computational pathology tools aid accurate cellular attribution of molecular signals. This innovative design with multiplex microRNA coupled with artificial intelligence has led to discovery of a quality control metric suitable for large scale application of the Cytosponge. Similar approaches could aid optimal interpretation of biomarkers for clinical use.

FUNDING: Funded by the NIHR Cambridge Biomedical Research Centre, the Medical Research Council, the Rosetrees and Stoneygate Trusts, and CRUK core grants.}, } @article {pmid35032334, year = {2022}, author = {Nemec-Venza, Z and Madden, C and Stewart, A and Liu, W and Novák, O and Pěnčík, A and Cuming, AC and Kamisugi, Y and Harrison, CJ}, title = {CLAVATA modulates auxin homeostasis and transport to regulate stem cell identity and plant shape in a moss.}, journal = {The New phytologist}, volume = {234}, number = {1}, pages = {149-163}, pmid = {35032334}, issn = {1469-8137}, mesh = {*Arabidopsis Proteins/genetics/metabolism ; *Bryophyta/metabolism ; *Bryopsida/genetics/metabolism ; Gene Expression Regulation, Plant ; Homeostasis ; Indoleacetic Acids/metabolism ; Stem Cells/metabolism ; }, abstract = {The CLAVATA pathway is a key regulator of stem cell function in the multicellular shoot tips of Arabidopsis, where it acts via the WUSCHEL transcription factor to modulate hormone homeostasis. Broad-scale evolutionary comparisons have shown that CLAVATA is a conserved regulator of land plant stem cell function, but CLAVATA acts independently of WUSCHEL-like (WOX) proteins in bryophytes. The relationship between CLAVATA, hormone homeostasis and the evolution of land plant stem cell functions is unknown. Here we show that in the moss, Physcomitrella (Physcomitrium patens), CLAVATA affects stem cell activity by modulating hormone homeostasis. CLAVATA pathway genes are expressed in the tip cells of filamentous tissues, regulating cell identity, filament branching, plant spread and auxin synthesis. The receptor-like kinase PpRPK2 plays the major role, and Pprpk2 mutants have abnormal responses to cytokinin, auxin and auxin transport inhibition, and show reduced expression of PIN auxin transporters. We propose a model whereby PpRPK2 modulates auxin gradients in filaments to determine stem cell identity and overall plant form. Our data indicate that CLAVATA-mediated auxin homeostasis is a fundamental property of plant stem cell function, probably exhibited by the last shared common ancestor of land plants.}, } @article {pmid35018470, year = {2022}, author = {von der Heyde, EL and Hallmann, A}, title = {Molecular and cellular dynamics of early embryonic cell divisions in Volvox carteri.}, journal = {The Plant cell}, volume = {34}, number = {4}, pages = {1326-1353}, pmid = {35018470}, issn = {1532-298X}, mesh = {Animals ; Cell Division/genetics ; *Volvox/genetics ; }, abstract = {Cell division is fundamental to all organisms and the green alga used here exhibits both key animal and plant functions. Specifically, we analyzed the molecular and cellular dynamics of early embryonic divisions of the multicellular green alga Volvox carteri (Chlamydomonadales). Relevant proteins related to mitosis and cytokinesis were identified in silico, the corresponding genes were cloned, fused to yfp, and stably expressed in Volvox, and the tagged proteins were studied by live-cell imaging. We reveal rearrangements of the microtubule cytoskeleton during centrosome separation, spindle formation, establishment of the phycoplast, and generation of previously unknown structures. The centrosomes participate in initiation of spindle formation and determination of spindle orientation. Although the nuclear envelope does not break down during early mitosis, intermixing of cytoplasm and nucleoplasm results in loss of nuclear identity. Finally, we present a model for mitosis in Volvox. Our study reveals enormous dynamics, clarifies spatio-temporal relationships of subcellular structures, and provides insight into the evolution of cell division.}, } @article {pmid35014399, year = {2021}, author = {Klein, S and Distel, LVR and Neuhuber, W}, title = {X-ray Dose-Enhancing Impact of Functionalized Au-Fe3O4 Nanoheterodimers on MCF-7 and A549 Multicellular Tumor Spheroids.}, journal = {ACS applied bio materials}, volume = {4}, number = {4}, pages = {3113-3123}, doi = {10.1021/acsabm.0c01494}, pmid = {35014399}, issn = {2576-6422}, mesh = {Biocompatible Materials/chemistry/*pharmacology ; Cell Survival/drug effects ; Ferric Compounds/chemistry/*pharmacology ; Gold/chemistry/*pharmacology ; Humans ; MCF-7 Cells ; Materials Testing ; Nanoparticles/*chemistry ; Particle Size ; Spheroids, Cellular/*drug effects ; *X-Rays ; }, abstract = {The efficiency of nanoparticle-enhanced radiotherapy was studied by loading MCF-7 and A549 multicellular tumor spheroids (MCTSs) with caffeic acid- and nitrosonium-functionalized Au-Fe3O4 nanoheterodimers (Au-Fe3O4 NHDs). Transmission electron microscope images of MCTS cross-sectional sections visualized the invasion and distribution of the nitrosonium- and caffeic acid-functionalized Au-Fe3O4 NHDs (NO- and CA-NHDs) in the A549 and MCF-7 MCTSs, whereas the iron content of the MCTSs were quantified using the ferrozine assay. The synergistic impact of intracellular NO- and CA-NHDs and X-ray irradiation on the growth dynamics of the A549 and MCF-7 MCTSs was surveyed by monitoring their temporal evolution under a light microscope over a period of 14 days. The emergence of hypoxia during the spheroid growth was followed by detecting the lactate efflux of MCTSs without and with NO- and CA-NHDs. The performance of the NO- and CA-NHDs as X-ray dose-enhancing agents in the A549 and MCF-7 MCTSs was clarified by performing clonogenic cell survival assays and determining the respective dose-modifying factors for X-ray doses of 0, 2, 4, and 6 Gy. The NO- and CA-NHDs were shown to perform as potent X-ray dose-enhancing agents in A549 and MCF-7 MCTSs. Moreover, the CA-NHDs boosted their radio-sensitizing efficacy by inhibiting the lactate efflux as impairing metabolic reprogramming. A synergistic effect on the MCTS destruction was observed for the combination of both NHDs since the surfactants differ in their antitumor effect.}, } @article {pmid35013306, year = {2022}, author = {Sforna, MC and Loron, CC and Demoulin, CF and François, C and Cornet, Y and Lara, YJ and Grolimund, D and Ferreira Sanchez, D and Medjoubi, K and Somogyi, A and Addad, A and Fadel, A and Compère, P and Baudet, D and Brocks, JJ and Javaux, EJ}, title = {Intracellular bound chlorophyll residues identify 1 Gyr-old fossils as eukaryotic algae.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {146}, pmid = {35013306}, issn = {2041-1723}, mesh = {Biological Evolution ; Chlorophyll/*chemistry/history ; Chlorophyta/anatomy & histology/classification/physiology/*ultrastructure ; Coordination Complexes/*chemistry ; Democratic Republic of the Congo ; Ecosystem ; Eukaryotic Cells ; *Fossils ; Geologic Sediments/analysis ; History, Ancient ; Microscopy, Electron, Transmission ; Nickel/chemistry ; Photosynthesis/*physiology ; Phylogeny ; Plant Cells/physiology/ultrastructure ; Tetrapyrroles/chemistry ; X-Ray Absorption Spectroscopy ; }, abstract = {The acquisition of photosynthesis is a fundamental step in the evolution of eukaryotes. However, few phototrophic organisms are unambiguously recognized in the Precambrian record. The in situ detection of metabolic byproducts in individual microfossils is the key for the direct identification of their metabolisms. Here, we report a new integrative methodology using synchrotron-based X-ray fluorescence and absorption. We evidence bound nickel-geoporphyrins moieties in low-grade metamorphic rocks, preserved in situ within cells of a ~1 Gyr-old multicellular eukaryote, Arctacellularia tetragonala. We identify these moieties as chlorophyll derivatives, indicating that A. tetragonala was a phototrophic eukaryote, one of the first unambiguous algae. This new approach, applicable to overmature rocks, creates a strong new proxy to understand the evolution of phototrophy and diversification of early ecosystems.}, } @article {pmid34999783, year = {2022}, author = {Leger, MM and Ros-Rocher, N and Najle, SR and Ruiz-Trillo, I}, title = {Rel/NF-κB Transcription Factors Emerged at the Onset of Opisthokonts.}, journal = {Genome biology and evolution}, volume = {14}, number = {1}, pages = {}, pmid = {34999783}, issn = {1759-6653}, mesh = {Animals ; *Eukaryota/metabolism ; *Evolution, Molecular ; *NF-kappa B/genetics/metabolism ; Transcription Factor RelA/genetics/metabolism ; Transcription Factor RelB/genetics/metabolism ; }, abstract = {The Rel/NF-κB transcription factor family has myriad roles in immunity, development, and differentiation in animals, and was considered a key innovation for animal multicellularity. Rel homology domain-containing proteins were previously hypothesized to have originated in a last common ancestor of animals and some of their closest unicellular relatives. However, key taxa were missing from previous analyses, necessitating a systematic investigation into the distribution and evolution of these proteins. Here, we address this knowledge gap by surveying taxonomically broad data from eukaryotes, with a special emphasis on lineages closely related to animals. We report an earlier origin for Rel/NF-κB proteins than previously described, in the last common ancestor of animals and fungi, and show that even in the sister group to fungi, these proteins contain elements that in animals are necessary for the subcellular regulation of Rel/NF-κB.}, } @article {pmid34998872, year = {2022}, author = {Kulkarni, P and Behal, A and Mohanty, A and Salgia, R and Nedelcu, AM and Uversky, VN}, title = {Co-opting disorder into order: Intrinsically disordered proteins and the early evolution of complex multicellularity.}, journal = {International journal of biological macromolecules}, volume = {201}, number = {}, pages = {29-36}, doi = {10.1016/j.ijbiomac.2021.12.182}, pmid = {34998872}, issn = {1879-0003}, mesh = {*Intrinsically Disordered Proteins ; *Volvox ; }, abstract = {Intrinsically disordered proteins (IDPs) are proteins that lack rigid structures yet play important roles in myriad biological phenomena. A distinguishing feature of IDPs is that they often mediate specific biological outcomes via multivalent weak cooperative interactions with multiple partners. Here, we show that several proteins specifically associated with processes that were key in the evolution of complex multicellularity in the lineage leading to the multicellular green alga Volvox carteri are IDPs. We suggest that, by rewiring cellular protein interaction networks, IDPs facilitated the co-option of ancestral pathways for specialized multicellular functions, underscoring the importance of IDPs in the early evolution of complex multicellularity.}, } @article {pmid34992624, year = {2021}, author = {Hemleben, V and Grierson, D and Borisjuk, N and Volkov, RA and Kovarik, A}, title = {Personal Perspectives on Plant Ribosomal RNA Genes Research: From Precursor-rRNA to Molecular Evolution.}, journal = {Frontiers in plant science}, volume = {12}, number = {}, pages = {797348}, pmid = {34992624}, issn = {1664-462X}, abstract = {The history of rDNA research started almost 90 years ago when the geneticist, Barbara McClintock observed that in interphase nuclei of maize the nucleolus was formed in association with a specific region normally located near the end of a chromosome, which she called the nucleolar organizer region (NOR). Cytologists in the twentieth century recognized the nucleolus as a common structure in all eukaryotic cells, using both light and electron microscopy and biochemical and genetic studies identified ribosomes as the subcellular sites of protein synthesis. In the mid- to late 1960s, the synthesis of nuclear-encoded rRNA was the only system in multicellular organisms where transcripts of known function could be isolated, and their synthesis and processing could be studied. Cytogenetic observations of NOR regions with altered structure in plant interspecific hybrids and detailed knowledge of structure and function of rDNA were prerequisites for studies of nucleolar dominance, epistatic interactions of rDNA loci, and epigenetic silencing. In this article, we focus on the early rDNA research in plants, performed mainly at the dawn of molecular biology in the 60 to 80-ties of the last century which presented a prequel to the modern genomic era. We discuss - from a personal view - the topics such as synthesis of rRNA precursor (35S pre-rRNA in plants), processing, and the organization of 35S and 5S rDNA. Cloning and sequencing led to the observation that the transcribed and processed regions of the rRNA genes vary enormously, even between populations and species, in comparison with the more conserved regions coding for the mature rRNAs. Epigenetic phenomena and the impact of hybridization and allopolyploidy on rDNA expression and homogenization are discussed. This historical view of scientific progress and achievements sets the scene for the other articles highlighting the immense progress in rDNA research published in this special issue of Frontiers in Plant Science on "Molecular organization, evolution, and function of ribosomal DNA."}, } @article {pmid34949534, year = {2022}, author = {Graham, AL and Schrom, EC and Metcalf, CJE}, title = {The evolution of powerful yet perilous immune systems.}, journal = {Trends in immunology}, volume = {43}, number = {2}, pages = {117-131}, pmid = {34949534}, issn = {1471-4981}, mesh = {Adaptation, Physiological ; Animals ; Biological Evolution ; *COVID-19 ; Cytokines/genetics ; Humans ; Immune System ; SARS-CoV-2 ; }, abstract = {The mammalian immune system packs serious punch against infection but can also cause harm: for example, coronavirus disease 2019 (COVID-19) made headline news of the simultaneous power and peril of human immune responses. In principle, natural selection leads to exquisite adaptation and therefore cytokine responsiveness that optimally balances the benefits of defense against its costs (e.g., immunopathology suffered and resources expended). Here, we illustrate how evolutionary biology can predict such optima and also help to explain when/why individuals exhibit apparently maladaptive immunopathological responses. Ultimately, we argue that the evolutionary legacies of multicellularity and life-history strategy, in addition to our coevolution with symbionts and our demographic history, together explain human susceptibility to overzealous, pathology-inducing cytokine responses. Evolutionary insight thereby complements molecular/cellular mechanistic insights into immunopathology.}, } @article {pmid34944066, year = {2021}, author = {Yeh, CY and Huang, WH and Chen, HC and Meir, YJ}, title = {Capturing Pluripotency and Beyond.}, journal = {Cells}, volume = {10}, number = {12}, pages = {}, pmid = {34944066}, issn = {2073-4409}, mesh = {Animals ; Blastocyst/metabolism ; Cell Differentiation/*genetics ; Cell Lineage/genetics ; Embryonic Development/*genetics ; Embryonic Stem Cells/cytology ; Gene Expression Regulation, Developmental/genetics ; Germ Layers/*growth & development ; Humans ; Mice ; Pluripotent Stem Cells/*cytology ; }, abstract = {During the development of a multicellular organism, the specification of different cell lineages originates in a small group of pluripotent cells, the epiblasts, formed in the preimplantation embryo. The pluripotent epiblast is protected from premature differentiation until exposure to inductive cues in strictly controlled spatially and temporally organized patterns guiding fetus formation. Epiblasts cultured in vitro are embryonic stem cells (ESCs), which recapitulate the self-renewal and lineage specification properties of their endogenous counterparts. The characteristics of totipotency, although less understood than pluripotency, are becoming clearer. Recent studies have shown that a minor ESC subpopulation exhibits expanded developmental potential beyond pluripotency, displaying a characteristic reminiscent of two-cell embryo blastomeres (2CLCs). In addition, reprogramming both mouse and human ESCs in defined media can produce expanded/extended pluripotent stem cells (EPSCs) similar to but different from 2CLCs. Further, the molecular roadmaps driving the transition of various potency states have been clarified. These recent key findings will allow us to understand eutherian mammalian development by comparing the underlying differences between potency network components during development. Using the mouse as a paradigm and recent progress in human PSCs, we review the epiblast's identity acquisition during embryogenesis and their ESC counterparts regarding their pluripotent fates and beyond.}, } @article {pmid34937533, year = {2021}, author = {Shilovsky, GA and Putyatina, TS and Markov, AV}, title = {Altruism and Phenoptosis as Programs Supported by Evolution.}, journal = {Biochemistry. Biokhimiia}, volume = {86}, number = {12}, pages = {1540-1552}, pmid = {34937533}, issn = {1608-3040}, mesh = {*Altruism ; Animals ; *Apoptosis ; *Biological Evolution ; *COVID-19 ; Humans ; Insecta/physiology ; *SARS-CoV-2 ; }, abstract = {Phenoptosis is a programmed death that has emerged in the process of evolution, sometimes taking the form of an altruistic program. In particular, it is believed to be a weapon against the spread of pandemics in the past and an obstacle in fighting pandemics in the present (COVID). However, on the evolutionary scale, deterministic death is not associated with random relationships (for example, bacteria with a particular mutation), but is a product of higher nervous activity or a consequence of established hierarchy that reaches its maximal expression in eusocial communities of Hymenoptera and highly social communities of mammals. Unlike a simple association of individuals, eusociality is characterized by the appearance of non-reproductive individuals as the highest form of altruism. In contrast to primitive programs for unicellular organisms, higher multicellular organisms are characterized by the development of behavior-based phenoptotic programs, especially in the case of reproduction-associated limitation of lifespan. Therefore, we can say that the development of altruism in the course of evolution of sociality leads in its extreme manifestation to phenoptosis. Development of mathematical models for the emergence of altruism and programmed death contributes to our understanding of mechanisms underlying these paradoxical counterproductive (harmful) programs. In theory, this model can be applied not only to insects, but also to other social animals and even to the human society. Adaptive death is an extreme form of altruism. We consider altruism and programmed death as programmed processes in the mechanistic and adaptive sense, respectively. Mechanistically, this is a program existing as a predetermined chain of certain responses, regardless of its adaptive value. As to its adaptive value (regardless of the degree of "phenoptoticity"), this is a characteristic of organisms that demonstrate high levels of kinship, social organization, and physical association typical for higher-order individuals, e.g., unicellular organisms forming colonies with some characteristics of multicellular animals or colonies of multicellular animals displaying features of supraorganisms.}, } @article {pmid34932575, year = {2021}, author = {Maltseva, AL and Varfolomeeva, MA and Gafarova, ER and Panova, MAZ and Mikhailova, NA and Granovitch, AI}, title = {Divergence together with microbes: A comparative study of the associated microbiomes in the closely related Littorina species.}, journal = {PloS one}, volume = {16}, number = {12}, pages = {e0260792}, pmid = {34932575}, issn = {1932-6203}, mesh = {Animals ; Bacteria/classification/genetics/*isolation & purification ; Environmental Microbiology ; *Genetic Variation ; *Microbiota ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Snails/classification/*microbiology ; Species Specificity ; }, abstract = {Any multicellular organism during its life is involved in relatively stable interactions with microorganisms. The organism and its microbiome make up a holobiont, possessing a unique set of characteristics and evolving as a whole system. This study aimed to evaluate the degree of the conservativeness of microbiomes associated with intertidal gastropods. We studied the composition and the geographic and phylogenetic variability of the gut and body surface microbiomes of five closely related sympatric Littorina (Neritrema) spp. and a more distant species, L. littorea, from the sister subgenus Littorina (Littorina). Although snail-associated microbiomes included many lineages (207-603), they were dominated by a small number of OTUs of the genera Psychromonas, Vibrio, and Psychrilyobacter. The geographic variability was greater than the interspecific differences at the same collection site. While the microbiomes of the six Littorina spp. did not differ at the high taxonomic level, the OTU composition differed between groups of cryptic species and subgenera. A few species-specific OTUs were detected within the collection sites; notably, such OTUs never dominated microbiomes. We conclude that the composition of the high-rank taxa of the associated microbiome ("scaffolding enterotype") is more evolutionarily conserved than the composition of the low-rank individual OTUs, which may be site- and / or species-specific.}, } @article {pmid34913456, year = {2022}, author = {Gurney, J and Simonet, C and Wollein Waldetoft, K and Brown, SP}, title = {Challenges and opportunities for cheat therapy in the control of bacterial infections.}, journal = {Natural product reports}, volume = {39}, number = {2}, pages = {325-334}, doi = {10.1039/d1np00053e}, pmid = {34913456}, issn = {1460-4752}, mesh = {*Bacterial Infections/drug therapy ; *Biological Evolution ; Humans ; }, abstract = {Covering: 1999 to 2021Bacterial pathogens can be highly social, communicating and cooperating within multi-cellular groups to make us sick. The requirement for collective action in pathogens presents novel therapeutic avenues that seek to undermine cooperative behavior, what we call here 'cheat therapies'. We review two broad avenues of cheat therapy: first, the introduction of genetically engineered 'cheat' strains (bio-control cheats), and second the chemical induction of 'cheat' behavior in the infecting pathogens (chemical-control cheats). Both genetically engineered and chemically induced cheats can socially exploit the cooperative wildtype infection, reducing pathogen burden and the severity of disease. We review the costs and benefits of cheat therapies, highlighting advantages of evolutionary robustness and also the challenges of low to moderate efficacy, compared to conventional antibiotic treatments. We end with a summary of what we see as the most valuable next steps, focusing on adjuvant treatments and use as alternate therapies for mild, self-resolving infections - allowing the reservation of current and highly effective antibiotics for more critical patient needs.}, } @article {pmid34890552, year = {2021}, author = {Brückner, A and Badroos, JM and Learsch, RW and Yousefelahiyeh, M and Kitchen, SA and Parker, J}, title = {Evolutionary assembly of cooperating cell types in an animal chemical defense system.}, journal = {Cell}, volume = {184}, number = {25}, pages = {6138-6156.e28}, doi = {10.1016/j.cell.2021.11.014}, pmid = {34890552}, issn = {1097-4172}, mesh = {Animals ; Benzoquinones/*metabolism ; Biological Evolution ; Biosynthetic Pathways ; Coleoptera/*metabolism ; Drosophila melanogaster/*metabolism ; Pheromones/*metabolism ; }, abstract = {How the functions of multicellular organs emerge from the underlying evolution of cell types is poorly understood. We deconstructed evolution of an organ novelty: a rove beetle gland that secretes a defensive cocktail. We show how gland function arose via assembly of two cell types that manufacture distinct compounds. One cell type, comprising a chemical reservoir within the abdomen, produces alkane and ester compounds. We demonstrate that this cell type is a hybrid of cuticle cells and ancient pheromone and adipocyte-like cells, executing its function via a mosaic of enzymes from each parental cell type. The second cell type synthesizes benzoquinones using a chimera of conserved cellular energy and cuticle formation pathways. We show that evolution of each cell type was shaped by coevolution between the two cell types, yielding a potent secretion that confers adaptive value. Our findings illustrate how cooperation between cell types arises, generating new, organ-level behaviors.}, } @article {pmid34884742, year = {2021}, author = {Troitskaya, O and Novak, D and Nushtaeva, A and Savinkova, M and Varlamov, M and Ermakov, M and Richter, V and Koval, O}, title = {EGFR Transgene Stimulates Spontaneous Formation of MCF7 Breast Cancer Cells Spheroids with Partly Loss of HER3 Receptor.}, journal = {International journal of molecular sciences}, volume = {22}, number = {23}, pages = {}, pmid = {34884742}, issn = {1422-0067}, mesh = {CD24 Antigen/metabolism ; Cell Culture Techniques, Three Dimensional ; *Genes, erbB-1 ; Humans ; Hyaluronan Receptors/metabolism ; *MCF-7 Cells ; Receptor, ErbB-3/*metabolism ; Rhodamine 123 ; *Spheroids, Cellular ; Transgenes ; Tumor Cells, Cultured ; }, abstract = {Multicellular spheroids with 3D cell-cell interactions are a useful model to simulate the growth conditions of cancer. There is evidence that in tumor spheroids, the expression of various essential molecules is changed compared to the adherent form of cell cultures. These changes include growth factor receptors and ABC transporters and result in the enhanced invasiveness of the cells and drug resistance. It is known that breast adenocarcinoma MCF7 cells can spontaneously form 3D spheroids and such spheroids are characterized by high expression of EGFR/HER2, while the natural phenotype of MCF7 cells is EGFR[low]/HER2[low]. Therefore, it was interesting to reveal if high epidermal growth factor receptor (EGFR) expression is sufficient for the conversion of adherent MCF7 to spheroids. In this study, an MCF7 cell line with high expression of EGFR was engineered using the retroviral transduction method. These MCF7-EGFR cells assembled in spheroids very quickly and grew predominantly as a 3D suspension culture with no special plates, scaffolds, growth supplements, or exogenous matrixes. These spheroids were characterized by a rounded shape with a well-defined external border and 100 µM median diameter. The sphere-forming ability of MCF7-EGFR cells was up to 5 times stronger than in MCF7[wt] cells. Thus, high EGFR expression was the initiation factor of conversion of adherent MCF7[wt] cells to spheroids. MCF7-EGFR spheroids were enriched by the cells with a cancer stem cell (CSC) phenotype CD24[-/low]/CD44[-] in comparison with parental MCF7[wt] cells and MCF7-EGFR adhesive cells. We suppose that these properties of MCF7-EGFR spheroids originate from the typical features of parental MCF7 cells. We showed the decreasing of HER3 receptors in MCF7-EGFR spheroids compared to that in MCF[wt] and in adherent MCF7-EGFR cells, and the same decrease was observed in the MCF7[wt] spheroids growing under the growth factors stimulation. To summarize, the expression of EGFR transgene in MCF7 cells stimulates rapid spheroids formation; these spheroids are enriched by CSC-like CD24[-]/CD44[-] cells, they partly lose HER3 receptors, and are characterized by a lower potency in drug resistance pomp activation compared to MCF7[wt]. These MCF7-EGFR spheroids are a useful cancer model for the development of anticancer drugs, including EGFR-targeted therapeutics.}, } @article {pmid34878516, year = {2022}, author = {Suissa, JS}, title = {Fern fronds that move like pine cones: humidity-driven motion of fertile leaflets governs the timing of spore dispersal in a widespread fern species.}, journal = {Annals of botany}, volume = {129}, number = {5}, pages = {519-528}, pmid = {34878516}, issn = {1095-8290}, mesh = {*Ferns/physiology ; Germ Cells, Plant ; Humidity ; Plant Cone ; Spores/physiology ; Spores, Fungal ; }, abstract = {BACKGROUND AND AIMS: The sensitive fern, Onoclea sensibilis, is a widespread species in eastern North America and has an atypical timing of spore dispersal among temperate ferns. During early summer, this dimorphic species produces heavily modified spore-bearing fronds with leaflets tightly enveloping their sporangia and spores. These fronds senesce and persist above ground as dead mature structures until the following early spring when the leaflets finally open and spores are dispersed. While this timing of spore dispersal has been observed for over 120 years, the structural mechanisms underpinning this phenology have remained elusive.

METHODS: Based on field observations, growth chamber manipulations and scanning electron microscopy, the mechanisms underlying this distinctive timing of spore dispersal in the sensitive fern were investigated.

KEY RESULTS: I show that fertile leaflets of the sensitive fern move in direct response to changes in humidity, exhibiting structural and functional parallels with multicellular hygromorphic structures in seed plants, such as pine cones. These parallels include differences in cellulose microfibril orientation in cells on the abaxial and adaxial sides of the leaflet. The dynamics of this hygroscopic movement concomitant with regular abscission zones along the pinnules and coordinated senescence lead to the specific timing of early spring spore dispersal in the sensitive fern.

CONCLUSIONS: While hygroscopic movement is common in seed-free plants, it mostly occurs in small structures that are either one or a few cells in size, such as the leptosporangium. Given its multicellular structure and integration across many cells and tissues, the movement and construction of the sensitive fern pinnules are more similar to structures in seed plants. The evolution of this complex trait in the sensitive fern efficiently regulates the timing of spore release, leading to early spring dispersal. This phenology likely gives gametophytes and subsequent sporophytes an advantage with early germination and growth.}, } @article {pmid34873026, year = {2021}, author = {Wade, J and Byrne, DJ and Ballentine, CJ and Drakesmith, H}, title = {Temporal variation of planetary iron as a driver of evolution.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {118}, number = {51}, pages = {}, pmid = {34873026}, issn = {1091-6490}, support = {MC_UU_00008/10/MRC_/Medical Research Council/United Kingdom ; MC_UU_12010/10/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Biological Availability ; *Biological Evolution ; Earth, Planet ; Ecosystem ; *Evolution, Planetary ; Genetic Variation ; Geology ; Host-Pathogen Interactions ; Iron/chemistry/*metabolism ; Oxidation-Reduction ; Siderophores/metabolism ; Water/chemistry/metabolism ; }, abstract = {Iron is an irreplaceable component of proteins and enzyme systems required for life. This need for iron is a well-characterized evolutionary mechanism for genetic selection. However, there is limited consideration of how iron bioavailability, initially determined by planetary accretion but fluctuating considerably at global scale over geological time frames, has shaped the biosphere. We describe influences of iron on planetary habitability from formation events >4 Gya and initiation of biochemistry from geochemistry through oxygenation of the atmosphere to current host-pathogen dynamics. By determining the iron and transition element distribution within the terrestrial planets, planetary core formation is a constraint on both the crustal composition and the longevity of surface water, hence a planet's habitability. As such, stellar compositions, combined with metallic core-mass fraction, may be an observable characteristic of exoplanets that relates to their ability to support life. On Earth, the stepwise rise of atmospheric oxygen effectively removed gigatons of soluble ferrous iron from habitats, generating evolutionary pressures. Phagocytic, infectious, and symbiotic behaviors, dating from around the Great Oxygenation Event, refocused iron acquisition onto biotic sources, while eukaryotic multicellularity allows iron recycling within an organism. These developments allow life to more efficiently utilize a scarce but vital nutrient. Initiation of terrestrial life benefitted from the biochemical properties of abundant mantle/crustal iron, but the subsequent loss of iron bioavailability may have been an equally important driver of compensatory diversity. This latter concept may have relevance for the predicted future increase in iron deficiency across the food chain caused by elevated atmospheric CO2.}, } @article {pmid34870903, year = {2021}, author = {Prostak, SM and Fritz-Laylin, LK}, title = {Laboratory Maintenance of the Chytrid Fungus Batrachochytrium dendrobatidis.}, journal = {Current protocols}, volume = {1}, number = {12}, pages = {e309}, doi = {10.1002/cpz1.309}, pmid = {34870903}, issn = {2691-1299}, mesh = {Amphibians ; Animals ; Batrachochytrium ; *Chytridiomycota ; Ecosystem ; Laboratories ; }, abstract = {The chytrid fungus Batrachochytrium dendrobatidis (Bd) is a causative agent of chytridiomycosis, a skin disease associated with amphibian population declines around the world. Despite the major impact Bd is having on global ecosystems, much of Bd's basic biology remains unstudied. In addition to revealing mechanisms driving the spread of chytridiomycosis, studying Bd can shed light on the evolution of key fungal traits because chytrid fungi, including Bd, diverged before the radiation of the Dikaryotic fungi (multicellular fungi and yeast). Studying Bd in the laboratory is, therefore, of growing interest to a wide range of scientists, ranging from herpetologists and disease ecologists to molecular, cell, and evolutionary biologists. This protocol describes how to maintain developmentally synchronized liquid cultures of Bd for use in the laboratory, how to grow Bd on solid media, as well as cryopreservation and revival of frozen stocks. © 2021 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Reviving cryopreserved Bd cultures Basic Protocol 2: Establishing synchronized liquid cultures of Bd Basic Protocol 3: Regular maintenance of synchronous Bd in liquid culture Alternate Protocol 1: Regular maintenance of asynchronous Bd in liquid culture Basic Protocol 4: Regular maintenance of synchronous Bd on solid medium Alternate Protocol 2: Starting a culture on solid medium from a liquid culture Basic Protocol 5: Cryopreservation of Bd.}, } @article {pmid34857936, year = {2021}, author = {Liu, K and Deng, S and Ye, C and Yao, Z and Wang, J and Gong, H and Liu, L and He, X}, title = {Mapping single-cell-resolution cell phylogeny reveals cell population dynamics during organ development.}, journal = {Nature methods}, volume = {18}, number = {12}, pages = {1506-1514}, pmid = {34857936}, issn = {1548-7105}, mesh = {Alleles ; Animals ; Animals, Genetically Modified ; Cell Division ; Cell Lineage ; Computational Biology/*methods ; DNA Replication ; Drosophila melanogaster/embryology/*metabolism ; Endonucleases/metabolism ; Likelihood Functions ; Male ; Microscopy/*methods ; Mutagenesis ; *Mutation ; Phenotype ; Phylogeny ; Saccharomyces cerevisiae/genetics ; Single-Cell Analysis ; }, abstract = {Mapping the cell phylogeny of a complex multicellular organism relies on somatic mutations accumulated from zygote to adult. Available cell barcoding methods can record about three mutations per barcode, enabling only low-resolution mapping of the cell phylogeny of complex organisms. Here we developed SMALT, a substitution mutation-aided lineage-tracing system that outperforms the available cell barcoding methods in mapping cell phylogeny. We applied SMALT to Drosophila melanogaster and obtained on average more than 20 mutations on a three-kilobase-pair barcoding sequence in early-adult cells. Using the barcoding mutations, we obtained high-quality cell phylogenetic trees, each comprising several thousand internal nodes with 84-93% median bootstrap support. The obtained cell phylogenies enabled a population genetic analysis that estimates the longitudinal dynamics of the number of actively dividing parental cells (Np) in each organ through development. The Np dynamics revealed the trajectory of cell births and provided insight into the balance of symmetric and asymmetric cell division.}, } @article {pmid34853303, year = {2021}, author = {Pennemann, FL and Mussabekova, A and Urban, C and Stukalov, A and Andersen, LL and Grass, V and Lavacca, TM and Holze, C and Oubraham, L and Benamrouche, Y and Girardi, E and Boulos, RE and Hartmann, R and Superti-Furga, G and Habjan, M and Imler, JL and Meignin, C and Pichlmair, A}, title = {Cross-species analysis of viral nucleic acid interacting proteins identifies TAOKs as innate immune regulators.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {7009}, pmid = {34853303}, issn = {2041-1723}, mesh = {Animals ; Antiviral Agents ; Drosophila melanogaster ; Evolution, Molecular ; Humans ; *Immunity, Innate ; Mice ; Nucleic Acids/*chemistry/*immunology ; Protein Serine-Threonine Kinases ; Proteomics ; RNA Interference ; RNA, Double-Stranded ; Species Specificity ; THP-1 Cells ; Viral Proteins/*chemistry/*immunology ; }, abstract = {The cell intrinsic antiviral response of multicellular organisms developed over millions of years and critically relies on the ability to sense and eliminate viral nucleic acids. Here we use an affinity proteomics approach in evolutionary distant species (human, mouse and fly) to identify proteins that are conserved in their ability to associate with diverse viral nucleic acids. This approach shows a core of orthologous proteins targeting viral genetic material and species-specific interactions. Functional characterization of the influence of 181 candidates on replication of 6 distinct viruses in human cells and flies identifies 128 nucleic acid binding proteins with an impact on virus growth. We identify the family of TAO kinases (TAOK1, -2 and -3) as dsRNA-interacting antiviral proteins and show their requirement for type-I interferon induction. Depletion of TAO kinases in mammals or flies leads to an impaired response to virus infection characterized by a reduced induction of interferon stimulated genes in mammals and impaired expression of srg1 and diedel in flies. Overall, our study shows a larger set of proteins able to mediate the interaction between viral genetic material and host factors than anticipated so far, attesting to the ancestral roots of innate immunity and to the lineage-specific pressures exerted by viruses.}, } @article {pmid34849891, year = {2021}, author = {Varahan, S and Laxman, S}, title = {Bend or break: how biochemically versatile molecules enable metabolic division of labor in clonal microbial communities.}, journal = {Genetics}, volume = {219}, number = {2}, pages = {}, pmid = {34849891}, issn = {1943-2631}, mesh = {Evolution, Molecular ; *Microbial Consortia ; *Microbial Interactions ; Yeasts/genetics/metabolism/physiology ; }, abstract = {In fluctuating nutrient environments, isogenic microbial cells transition into "multicellular" communities composed of phenotypically heterogeneous cells, showing functional specialization. In fungi (such as budding yeast), phenotypic heterogeneity is often described in the context of cells switching between different morphotypes (e.g., yeast to hyphae/pseudohyphae or white/opaque transitions in Candida albicans). However, more fundamental forms of metabolic heterogeneity are seen in clonal Saccharomyces cerevisiae communities growing in nutrient-limited conditions. Cells within such communities exhibit contrasting, specialized metabolic states, and are arranged in distinct, spatially organized groups. In this study, we explain how such an organization can stem from self-organizing biochemical reactions that depend on special metabolites. These metabolites exhibit plasticity in function, wherein the same metabolites are metabolized and utilized for distinct purposes by different cells. This in turn allows cell groups to function as specialized, interdependent cross-feeding systems which support distinct metabolic processes. Exemplifying a system where cells exhibit either gluconeogenic or glycolytic states, we highlight how available metabolites can drive favored biochemical pathways to produce new, limiting resources. These new resources can themselves be consumed or utilized distinctly by cells in different metabolic states. This thereby enables cell groups to sustain contrasting, even apparently impossible metabolic states with stable transcriptional and metabolic signatures for a given environment, and divide labor in order to increase community fitness or survival. We speculate on possible evolutionary implications of such metabolic specialization and division of labor in isogenic microbial communities.}, } @article {pmid34848727, year = {2021}, author = {Benaissa, H and Ounoughi, K and Aujard, I and Fischer, E and Goïame, R and Nguyen, J and Tebo, AG and Li, C and Le Saux, T and Bertolin, G and Tramier, M and Danglot, L and Pietrancosta, N and Morin, X and Jullien, L and Gautier, A}, title = {Engineering of a fluorescent chemogenetic reporter with tunable color for advanced live-cell imaging.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {6989}, pmid = {34848727}, issn = {2041-1723}, mesh = {Animals ; Biocompatible Materials ; Biosensing Techniques ; Color ; Coloring Agents ; Diagnostic Imaging/*methods ; Electronics ; Female ; *Fluorescence ; Fluorescence Resonance Energy Transfer ; Fluorescent Dyes ; Green Fluorescent Proteins ; Male ; Neurons ; Protein Engineering/*methods ; Rats ; Rats, Sprague-Dawley ; }, abstract = {Biocompatible fluorescent reporters with spectral properties spanning the entire visible spectrum are indispensable tools for imaging the biochemistry of living cells and organisms in real time. Here, we report the engineering of a fluorescent chemogenetic reporter with tunable optical and spectral properties. A collection of fluorogenic chromophores with various electronic properties enables to generate bimolecular fluorescent assemblies that cover the visible spectrum from blue to red using a single protein tag engineered and optimized by directed evolution and rational design. The ability to tune the fluorescence color and properties through simple molecular modulation provides a broad experimental versatility for imaging proteins in live cells, including neurons, and in multicellular organisms, and opens avenues for optimizing Förster resonance energy transfer (FRET) biosensors in live cells. The ability to tune the spectral properties and fluorescence performance enables furthermore to match the specifications and requirements of advanced super-resolution imaging techniques.}, } @article {pmid34841798, year = {2021}, author = {Yu, D and Cao, H and Wang, X}, title = {[Advances and applications of organoids: a review].}, journal = {Sheng wu gong cheng xue bao = Chinese journal of biotechnology}, volume = {37}, number = {11}, pages = {3961-3974}, doi = {10.13345/j.cjb.200764}, pmid = {34841798}, issn = {1872-2075}, mesh = {*Gene Editing ; Humans ; Models, Biological ; *Organoids ; Regenerative Medicine ; Stem Cells ; }, abstract = {Novel model systems have provided powerful tools for the research of human biology. Despite of being widely used, the conventional research models could not precisely describe the human physiological phenomenon. Organoids are three-dimensional multicellular aggregates derived from stem cells or organ progenitors that could differentiate and self-organize to recapitulate some specific functionalities and architectures of their in vivo counterpart organs. Organoids can be used to simulate organogenesis because of their human origin. In addition, the genomic stability of organoids could be well maintained during long-term amplification in vitro. Moreover, organoids can be cryopreserved as a live biobank for high-throughput screening. Combinatorial use of organoids with other emerging technologies (e.g. gene editing, organ-on-a-chip and single-cell RNA sequencing) could overcome the bottlenecks of conventional models and provide valuable information for disease modelling, pharmaceutical research, precision medicine and regenerative medicine at the organ level. This review summarizes the classifications, characteristics, current applications, combined use with other technologies and future prospects of organoids.}, } @article {pmid34838795, year = {2022}, author = {Tverskoi, D and Gavrilets, S}, title = {The evolution of germ-soma specialization under different genetic and environmental effects.}, journal = {Journal of theoretical biology}, volume = {534}, number = {}, pages = {110964}, doi = {10.1016/j.jtbi.2021.110964}, pmid = {34838795}, issn = {1095-8541}, mesh = {*Biological Evolution ; Cell Differentiation ; Climate ; Fertility ; Humans ; *Models, Biological ; }, abstract = {Division of labor exists at different levels of biological organization - from cell colonies to human societies. One of the simplest examples of the division of labor in multicellular organisms is germ-soma specialization, which plays a key role in the evolution of organismal complexity. Here we formulate and study a general mathematical model exploring the emergence of germ-soma specialization in colonies of cells. We consider a finite population of colonies competing for resources. Colonies are of the same size and are composed by asexually reproducing haploid cells. Each cell can contribute to activity and fecundity of the colony, these contributions are traded-off. We assume that all cells within a colony are genetically identical but gene effects on fecundity and activity are influenced by variation in the microenvironment experienced by individual cells. Through analytical theory and evolutionary agent-based modeling we show that the shape of the trade-off relation between somatic and reproductive functions, the type and extent of variation in within-colony microenvironment, and, in some cases, the number of genes involved, are important predictors of the extent of germ-soma specialization. Specifically, increasing convexity of the trade-off relation, the number of different environmental gradients acting within a colony, and the number of genes (in the case of random microenvironmental effects) promote the emergence of germ-soma specialization. Overall our results contribute towards a better understanding of the role of genetic, environmental, and microenvironmental factors in the evolution of germ-soma specialization.}, } @article {pmid34830470, year = {2021}, author = {Kertmen, A and Petrenko, I and Schimpf, C and Rafaja, D and Petrova, O and Sivkov, V and Nekipelov, S and Fursov, A and Stelling, AL and Heimler, K and Rogoll, A and Vogt, C and Ehrlich, H}, title = {Calcite Nanotuned Chitinous Skeletons of Giant Ianthella basta Marine Demosponge.}, journal = {International journal of molecular sciences}, volume = {22}, number = {22}, pages = {}, pmid = {34830470}, issn = {1422-0067}, mesh = {Animals ; Aquatic Organisms/*chemistry ; Biomineralization ; Calcium Carbonate/*chemistry ; Chitin/chemistry ; Porifera/*chemistry ; Skeleton/*chemistry ; Spectroscopy, Fourier Transform Infrared ; Tissue Scaffolds/chemistry ; X-Ray Diffraction ; }, abstract = {Marine sponges were among the first multicellular organisms on our planet and have survived to this day thanks to their unique mechanisms of chemical defense and the specific design of their skeletons, which have been optimized over millions of years of evolution to effectively inhabit the aquatic environment. In this work, we carried out studies to elucidate the nature and nanostructural organization of three-dimensional skeletal microfibers of the giant marine demosponge Ianthella basta, the body of which is a micro-reticular, durable structure that determines the ideal filtration function of this organism. For the first time, using the battery of analytical tools including three-dimensional micro-X-ray Fluorescence (3D-µXRF), X-ray diffraction (XRD), infra-red (FTIR), Raman and Near Edge X-ray Fine Structure (NEXAFS) spectroscopy, we have shown that biomineral calcite is responsible for nano-tuning the skeletal fibers of this sponge species. This is the first report on the presence of a calcitic mineral phase in representatives of verongiid sponges which belong to the class Demospongiae. Our experimental data suggest a possible role for structural amino polysaccharide chitin as a template for calcification. Our study suggests further experiments to elucidate both the origin of calcium carbonate inside the skeleton of this sponge and the mechanisms of biomineralization in the surface layers of chitin microfibers saturated with bromotyrosines, which have effective antimicrobial properties and are responsible for the chemical defense of this organism. The discovery of the calcified phase in the chitinous template of I. basta skeleton is expected to broaden the knowledge in biomineralization science where the calcium carbonate is regarded as a valuable material for applications in biomedicine, environmental science, and even in civil engineering.}, } @article {pmid34830263, year = {2021}, author = {Pereira, PHS and Garcia, CRS}, title = {Evidence of G-Protein-Coupled Receptors (GPCR) in the Parasitic Protozoa Plasmodium falciparum-Sensing the Host Environment and Coupling within Its Molecular Signaling Toolkit.}, journal = {International journal of molecular sciences}, volume = {22}, number = {22}, pages = {}, pmid = {34830263}, issn = {1422-0067}, mesh = {Animals ; Antimalarials/pharmacology/therapeutic use ; Calcium/metabolism ; Calcium Signaling/drug effects/*physiology ; Host-Parasite Interactions/*physiology ; Humans ; Malaria, Falciparum/drug therapy/*metabolism/parasitology ; Molecular Targeted Therapy/methods ; Perception/drug effects/*physiology ; Plasmodium falciparum/*metabolism ; Protein Binding ; Protozoan Proteins/*metabolism ; Receptors, G-Protein-Coupled/antagonists & inhibitors/*metabolism ; }, abstract = {Throughout evolution, the need for single-celled organisms to associate and form a single cluster of cells has had several evolutionary advantages. In complex, multicellular organisms, each tissue or organ has a specialty and function that make life together possible, and the organism as a whole needs to act in balance and adapt to changes in the environment. Sensory organs are essential for connecting external stimuli into a biological response, through the senses: sight, smell, taste, hearing, and touch. The G-protein-coupled receptors (GPCRs) are responsible for many of these senses and therefore play a key role in the perception of the cells' external environment, enabling interaction and coordinated development between each cell of a multicellular organism. The malaria-causing protozoan parasite, Plasmodium falciparum, has a complex life cycle that is extremely dependent on a finely regulated cellular signaling machinery. In this review, we summarize strong evidence and the main candidates of GPCRs in protozoan parasites. Interestingly, one of these GPCRs is a sensor for K[+] shift in Plasmodium falciparum, PfSR25. Studying this family of proteins in P. falciparum could have a significant impact, both on understanding the history of the evolution of GPCRs and on finding new targets for antimalarials.}, } @article {pmid34814752, year = {2021}, author = {Irisarri, I and Darienko, T and Pröschold, T and Fürst-Jansen, JMR and Jamy, M and de Vries, J}, title = {Unexpected cryptic species among streptophyte algae most distant to land plants.}, journal = {Proceedings. Biological sciences}, volume = {288}, number = {1963}, pages = {20212168}, pmid = {34814752}, issn = {1471-2954}, mesh = {*Chlorophyta/genetics ; *Embryophyta/genetics ; Evolution, Molecular ; Genome ; Phylogeny ; Plants/genetics ; }, abstract = {Streptophytes are one of the major groups of the green lineage (Chloroplastida or Viridiplantae). During one billion years of evolution, streptophytes have radiated into an astounding diversity of uni- and multicellular green algae as well as land plants. Most divergent from land plants is a clade formed by Mesostigmatophyceae, Spirotaenia spp. and Chlorokybophyceae. All three lineages are species-poor and the Chlorokybophyceae consist of a single described species, Chlorokybus atmophyticus. In this study, we used phylogenomic analyses to shed light into the diversity within Chlorokybus using a sampling of isolates across its known distribution. We uncovered a consistent deep genetic structure within the Chlorokybus isolates, which prompted us to formally extend the Chlorokybophyceae by describing four new species. Gene expression differences among Chlorokybus species suggest certain constitutive variability that might influence their response to environmental factors. Failure to account for this diversity can hamper comparative genomic studies aiming to understand the evolution of stress response across streptophytes. Our data highlight that future studies on the evolution of plant form and function can tap into an unknown diversity at key deep branches of the streptophytes.}, } @article {pmid34811380, year = {2021}, author = {Yamashita, S and Yamamoto, K and Matsuzaki, R and Suzuki, S and Yamaguchi, H and Hirooka, S and Minakuchi, Y and Miyagishima, SY and Kawachi, M and Toyoda, A and Nozaki, H}, title = {Genome sequencing of the multicellular alga Astrephomene provides insights into convergent evolution of germ-soma differentiation.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {22231}, pmid = {34811380}, issn = {2045-2322}, mesh = {Algal Proteins/genetics/metabolism ; *Biological Evolution ; Cell Differentiation/*genetics ; Chlorophyceae/*genetics ; Chlorophyta/*genetics ; Germ Cells ; Volvox/genetics ; Whole Genome Sequencing ; }, abstract = {Germ-soma differentiation evolved independently in many eukaryotic lineages and contributed to complex multicellular organizations. However, the molecular genetic bases of such convergent evolution remain unresolved. Two multicellular volvocine green algae, Volvox and Astrephomene, exhibit convergent evolution of germ-soma differentiation. The complete genome sequence is now available for Volvox, while genome information is scarce for Astrephomene. Here, we generated the de novo whole genome sequence of Astrephomene gubernaculifera and conducted RNA-seq analysis of isolated somatic and reproductive cells. In Volvox, tandem duplication and neofunctionalization of the ancestral transcription factor gene (RLS1/rlsD) might have led to the evolution of regA, the master regulator for Volvox germ-soma differentiation. However, our genome data demonstrated that Astrephomene has not undergone tandem duplication of the RLS1/rlsD homolog or acquisition of a regA-like gene. Our RNA-seq analysis revealed the downregulation of photosynthetic and anabolic gene expression in Astrephomene somatic cells, as in Volvox. Among genes with high expression in somatic cells of Astrephomene, we identified three genes encoding putative transcription factors, which may regulate somatic cell differentiation. Thus, the convergent evolution of germ-soma differentiation in the volvocine algae may have occurred by the acquisition of different regulatory circuits that generate a similar division of labor.}, } @article {pmid34789585, year = {2021}, author = {Miller, EA and Leidholt, S and Galvin, T and Norton, A and Van Houtan, KS and Vega Thurber, R and Boustany, A}, title = {Electron microscopy reveals viral-like particles and mitochondrial degradation in scombrid puffy snout syndrome.}, journal = {Diseases of aquatic organisms}, volume = {147}, number = {}, pages = {25-31}, doi = {10.3354/dao03634}, pmid = {34789585}, issn = {0177-5103}, mesh = {Animals ; Eukaryota ; Fishes ; Microscopy, Electron/veterinary ; *Mitophagy ; *Perciformes ; }, abstract = {Aquaculture is an increasingly important food resource, but its sustainability is often limited by disease. In Scombridae fishes, puffy snout syndrome (PSS) is a debilitating condition where tumor-like collagenous growths form around the eyes, nares, and mandibles which impair vision and feeding and frequently lead to mortality. While PSS is considered an infectious or metabolic disease, no disease agents or promoters have been identified. Here, we used electron microscopy (EM) to describe the cellular pathology and search for etiological agents of PSS in Pacific mackerel Scomber japonicus, the first use of this approach for PSS. We examined aquaculture specimens across a range of apparent PSS severity, comparing the results to both wild and aquaculture asymptomatic mackerel. EM imagery consistently revealed viral-like particles in PSS samples, as well as the uniform absence of bacteria, protists, fungi, and other multicellular parasites. In addition to viral-like particles, symptomatic fish had a higher mean percentage of swollen and disintegrating mitochondria than both asymptomatic aquaculture and wild mackerel. This suggests that degraded mitochondria may be related to PSS and could be important to further understanding the origin, promoters, and prevention of PSS. This study serves as a first step in identifying the etiological agents of PSS.}, } @article {pmid34788294, year = {2021}, author = {Fortunato, A and Fleming, A and Aktipis, A and Maley, CC}, title = {Upregulation of DNA repair genes and cell extrusion underpin the remarkable radiation resistance of Trichoplax adhaerens.}, journal = {PLoS biology}, volume = {19}, number = {11}, pages = {e3001471}, pmid = {34788294}, issn = {1545-7885}, support = {U54 CA217376/CA/NCI NIH HHS/United States ; R01 CA185138/CA/NCI NIH HHS/United States ; U2C CA233254/CA/NCI NIH HHS/United States ; P01 CA091955/CA/NCI NIH HHS/United States ; R01 CA170595/CA/NCI NIH HHS/United States ; R01 CA140657/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; DNA Damage/genetics/radiation effects ; DNA Repair/*genetics/radiation effects ; Gene Expression Regulation/radiation effects ; Placozoa/anatomy & histology/*genetics/radiation effects ; Radiation Exposure ; Radiation Tolerance/*genetics ; Sequence Analysis, DNA ; Up-Regulation/*genetics/radiation effects ; Whole Genome Sequencing ; X-Rays ; }, abstract = {Trichoplax adhaerens is the simplest multicellular animal with tissue differentiation and somatic cell turnover. Like all other multicellular organisms, it should be vulnerable to cancer, yet there have been no reports of cancer in T. adhaerens or any other placozoan. We investigated the cancer resistance of T. adhaerens, discovering that they are able to tolerate high levels of radiation damage (218.6 Gy). To investigate how T. adhaerens survive levels of radiation that are lethal to other animals, we examined gene expression after the X-ray exposure, finding overexpression of genes involved in DNA repair and apoptosis including the MDM2 gene. We also discovered that T. adhaerens extrudes clusters of inviable cells after X-ray exposure. T. adhaerens is a valuable model organism for studying the molecular, genetic, and tissue-level mechanisms underlying cancer suppression.}, } @article {pmid34769394, year = {2021}, author = {Marijuán, PC and Navarro, J}, title = {From Molecular Recognition to the "Vehicles" of Evolutionary Complexity: An Informational Approach.}, journal = {International journal of molecular sciences}, volume = {22}, number = {21}, pages = {}, pmid = {34769394}, issn = {1422-0067}, mesh = {Animals ; *Biological Evolution ; Computational Biology/*methods ; Humans ; *Metabolic Networks and Pathways ; *Mutation ; Signal Transduction ; }, abstract = {Countless informational proposals and models have explored the singular characteristics of biological systems: from the initial choice of information terms in the early days of molecular biology to the current bioinformatic avalanche in this "omic" era. However, this was conducted, most often, within partial, specialized scopes or just metaphorically. In this paper, we attempt a consistent informational discourse, initially based on the molecular recognition paradigm, which addresses the main stages of biological organization in a new way. It considers the interconnection between signaling systems and information flows, between informational architectures and biomolecular codes, between controlled cell cycles and multicellular complexity. It also addresses, in a new way, a central issue: how new evolutionary paths are opened by the cumulated action of multiple variation engines or mutational 'vehicles' evolved for the genomic exploration of DNA sequence space. Rather than discussing the possible replacement, extension, or maintenance of traditional neo-Darwinian tenets, a genuine informational approach to evolutionary phenomena is advocated, in which systemic variation in the informational architectures may induce differential survival (self-construction, self-maintenance, and reproduction) of biological agents within their open ended environment.}, } @article {pmid34769071, year = {2021}, author = {Vinogradov, AE and Anatskaya, OV}, title = {Growth of Biological Complexity from Prokaryotes to Hominids Reflected in the Human Genome.}, journal = {International journal of molecular sciences}, volume = {22}, number = {21}, pages = {}, pmid = {34769071}, issn = {1422-0067}, mesh = {Animals ; Epigenesis, Genetic ; *Evolution, Molecular ; *Gene Regulatory Networks ; *Genome, Human ; Hominidae/genetics ; Humans ; Multigene Family ; Oncogenes ; Prokaryotic Cells/metabolism ; Transcription Factors/genetics ; }, abstract = {The growth of complexity in evolution is a most intriguing phenomenon. Using gene phylostratigraphy, we showed this growth (as reflected in regulatory mechanisms) in the human genome, tracing the path from prokaryotes to hominids. Generally, the different regulatory gene families expanded at different times, yet only up to the Euteleostomi (bony vertebrates). The only exception was the expansion of transcription factors (TF) in placentals; however, we argue that this was not related to increase in general complexity. Surprisingly, although TF originated in the Prokaryota while chromatin appeared only in the Eukaryota, the expansion of epigenetic factors predated the expansion of TF. Signaling receptors, tumor suppressors, oncogenes, and aging- and disease-associated genes (indicating vulnerabilities in terms of complex organization and strongly enrichment in regulatory genes) also expanded only up to the Euteleostomi. The complexity-related gene properties (protein size, number of alternative splicing mRNA, length of untranslated mRNA, number of biological processes per gene, number of disordered regions in a protein, and density of TF-TF interactions) rose in multicellular organisms and declined after the Euteleostomi, and possibly earlier. At the same time, the speed of protein sequence evolution sharply increased in the genes that originated after the Euteleostomi. Thus, several lines of evidence indicate that molecular mechanisms of complexity growth were changing with time, and in the phyletic lineage leading to humans, the most salient shift occurred after the basic vertebrate body plan was fixed with bony skeleton. The obtained results can be useful for evolutionary medicine.}, } @article {pmid34752334, year = {2021}, author = {Pereira, PHS and Garcia, CRS and Bouvier, M}, title = {Identifying Plasmodium falciparum receptor activation using bioluminescence resonance energy transfer (BRET)-based biosensors in HEK293 cells.}, journal = {Methods in cell biology}, volume = {166}, number = {}, pages = {223-233}, doi = {10.1016/bs.mcb.2021.06.018}, pmid = {34752334}, issn = {0091-679X}, mesh = {*Biosensing Techniques ; Energy Transfer ; HEK293 Cells ; Humans ; *Plasmodium falciparum/metabolism ; Receptors, G-Protein-Coupled/genetics/metabolism ; }, abstract = {Throughout evolution the need for unicellular organisms to associate and form a single cluster of cells had several evolutionary advantages. G protein coupled receptors (GPCRs) are responsible for a large part of the senses that allow this clustering to succeed, playing a fundamental role in the perception of cell's external environment, enabling the interaction and coordinated development between each cell of a multicellular organism. GPCRs are not exclusive to complex multicellular organisms. In single-celled organisms, GPCRs are also present and have a similar function of detecting changes in the external environment and transforming them into a biological response. There are no reports of GPCRs in parasitic protozoa, such as the Plasmodium genus, and the identification of a protein of this family in P. falciparum would have a significant impact both on the understanding of the basic biology of the parasite and on the history of the evolution of GPCRs. The protocol described here was successfully applied to study a GPCR candidate in P. falciparum for the first time, and we hope that it helps other groups to use the same approach to study this deadly parasite.}, } @article {pmid34740967, year = {2021}, author = {Krespach, MKC and Stroe, MC and Flak, M and Komor, AJ and Nietzsche, S and Sasso, S and Hertweck, C and Brakhage, AA}, title = {Bacterial marginolactones trigger formation of algal gloeocapsoids, protective aggregates on the verge of multicellularity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {118}, number = {45}, pages = {}, pmid = {34740967}, issn = {1091-6490}, mesh = {*Cell Aggregation ; Chlamydomonas reinhardtii/*physiology/ultrastructure ; Macrolides/metabolism ; Microbial Interactions ; Streptomyces/metabolism ; }, abstract = {Photosynthetic microorganisms including the green alga Chlamydomonas reinhardtii are essential to terrestrial habitats as they start the carbon cycle by conversion of CO2 to energy-rich organic carbohydrates. Terrestrial habitats are densely populated, and hence, microbial interactions mediated by natural products are inevitable. We previously discovered such an interaction between Streptomyces iranensis releasing the marginolactone azalomycin F in the presence of C. reinhardtii Whether the alga senses and reacts to azalomycin F remained unknown. Here, we report that sublethal concentrations of azalomycin F trigger the formation of a protective multicellular structure by C. reinhardtii, which we named gloeocapsoid. Gloeocapsoids contain several cells which share multiple cell membranes and cell walls and are surrounded by a spacious matrix consisting of acidic polysaccharides. After azalomycin F removal, gloeocapsoid aggregates readily disassemble, and single cells are released. The presence of marginolactone biosynthesis gene clusters in numerous streptomycetes, their ubiquity in soil, and our observation that other marginolactones such as desertomycin A and monazomycin also trigger the formation of gloeocapsoids suggests a cross-kingdom competition with ecological relevance. Furthermore, gloeocapsoids allow for the survival of C. reinhardtii at alkaline pH and otherwise lethal concentrations of azalomycin F. Their structure and polysaccharide matrix may be ancestral to the complex mucilage formed by multicellular members of the Chlamydomonadales such as Eudorina and Volvox Our finding suggests that multicellularity may have evolved to endure the presence of harmful competing bacteria. Additionally, it underlines the importance of natural products as microbial cues, which initiate interesting ecological scenarios of attack and counter defense.}, } @article {pmid34740727, year = {2022}, author = {Quan, X and Kato, D and Daria, V and Matoba, O and Wake, H}, title = {Holographic microscope and its biological application.}, journal = {Neuroscience research}, volume = {179}, number = {}, pages = {57-64}, doi = {10.1016/j.neures.2021.10.012}, pmid = {34740727}, issn = {1872-8111}, mesh = {Animals ; *Holography/methods ; Mice ; Neurons/physiology ; Optogenetics/methods ; Photic Stimulation/methods ; Photons ; }, abstract = {Holographic structured illumination combined with optogenetics enables patterned stimulation of neurons and glial cells in an intact living brain. Moreover, in vivo functional imaging of cellular activity with recent advanced microscope technologies allows for visualization of the cellular responses during learning, emotion and cognition. Integrating these techniques can be used to verify the link between cell function and behavior output. However, there are technical limitations to stimulate multiple cells with high spatial and temporal resolution with available techniques of optogenetic stimulation. Here, we summarized a two-photon microscope combined with holographic system to stimulate multiple cells with high spatial and temporal resolution for living mice and their biological application.}, } @article {pmid34725037, year = {2021}, author = {Hakala, SM and Meurville, MP and Stumpe, M and LeBoeuf, AC}, title = {Biomarkers in a socially exchanged /fluid reflect colony maturity, behavior, and distributed metabolism.}, journal = {eLife}, volume = {10}, number = {}, pages = {}, pmid = {34725037}, issn = {2050-084X}, mesh = {Animals ; Ants/metabolism/*physiology ; Biomarkers/*metabolism ; Social Behavior ; }, abstract = {In cooperative systems exhibiting division of labor, such as microbial communities, multicellular organisms, and social insect colonies, individual units share costs and benefits through both task specialization and exchanged materials. Socially exchanged fluids, like seminal fluid and milk, allow individuals to molecularly influence conspecifics. Many social insects have a social circulatory system, where food and endogenously produced molecules are transferred mouth-to-mouth (stomodeal trophallaxis), connecting all the individuals in the society. To understand how these endogenous molecules relate to colony life, we used quantitative proteomics to investigate the trophallactic fluid within colonies of the carpenter ant Camponotus floridanus. We show that different stages of the colony life cycle circulate different types of proteins: young colonies prioritize direct carbohydrate processing; mature colonies prioritize accumulation and transmission of stored resources. Further, colonies circulate proteins implicated in oxidative stress, ageing, and social insect caste determination, potentially acting as superorganismal hormones. Brood-caring individuals that are also closer to the queen in the social network (nurses) showed higher abundance of oxidative stress-related proteins. Thus, trophallaxis behavior could provide a mechanism for distributed metabolism in social insect societies. The ability to thoroughly analyze the materials exchanged between cooperative units makes social insect colonies useful models to understand the evolution and consequences of metabolic division of labor at other scales.}, } @article {pmid34716269, year = {2021}, author = {Yang, H and Pegoraro, AF and Han, Y and Tang, W and Abeyaratne, R and Bi, D and Guo, M}, title = {Configurational fingerprints of multicellular living systems.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {118}, number = {44}, pages = {}, pmid = {34716269}, issn = {1091-6490}, support = {R01 GM140108/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Biophysical Phenomena/*physiology ; Cell Cycle ; Cell Movement ; Cell Proliferation ; Epithelial Cells/cytology ; Humans ; Image Processing, Computer-Assisted/*methods ; Morphogenesis ; Neoplasms ; Organ Specificity/*physiology ; *Phase Transition ; Spheroids, Cellular/cytology ; Wound Healing ; }, abstract = {Cells cooperate as groups to achieve structure and function at the tissue level, during which specific material characteristics emerge. Analogous to phase transitions in classical physics, transformations in the material characteristics of multicellular assemblies are essential for a variety of vital processes including morphogenesis, wound healing, and cancer. In this work, we develop configurational fingerprints of particulate and multicellular assemblies and extract volumetric and shear order parameters based on this fingerprint to quantify the system disorder. Theoretically, these two parameters form a complete and unique pair of signatures for the structural disorder of a multicellular system. The evolution of these two order parameters offers a robust and experimentally accessible way to map the phase transitions in expanding cell monolayers and during embryogenesis and invasion of epithelial spheroids.}, } @article {pmid34716098, year = {2022}, author = {Bogaert, KA and Blomme, J and Beeckman, T and De Clerck, O}, title = {Auxin's origin: do PILS hold the key?.}, journal = {Trends in plant science}, volume = {27}, number = {3}, pages = {227-236}, doi = {10.1016/j.tplants.2021.09.008}, pmid = {34716098}, issn = {1878-4372}, mesh = {Biological Transport ; *Indoleacetic Acids/metabolism ; *Membrane Transport Proteins/genetics/metabolism ; Plants/genetics/metabolism ; }, abstract = {Auxin is a key regulator of many developmental processes in land plants and plays a strikingly similar role in the phylogenetically distant brown seaweeds. Emerging evidence shows that the PIN and PIN-like (PILS) auxin transporter families have preceded the evolution of the canonical auxin response pathway. A wide conservation of PILS-mediated auxin transport, together with reports of auxin function in unicellular algae, would suggest that auxin function preceded the advent of multicellularity. We find that PIN and PILS transporters form two eukaryotic subfamilies within a larger bacterial family. We argue that future functional characterisation of algal PIN and PILS transporters can shed light on a common origin of an auxin function followed by independent co-option in a multicellular context.}, } @article {pmid34714532, year = {2022}, author = {Cao, Y}, title = {Neural is Fundamental: Neural Stemness as the Ground State of Cell Tumorigenicity and Differentiation Potential.}, journal = {Stem cell reviews and reports}, volume = {18}, number = {1}, pages = {37-55}, pmid = {34714532}, issn = {2629-3277}, mesh = {Carcinogenesis/genetics ; Cell Differentiation/genetics ; *Germ Layers ; Humans ; *Neural Stem Cells ; }, abstract = {Tumorigenic cells are similar to neural stem cells or embryonic neural cells in regulatory networks, tumorigenicity and pluripotent differentiation potential. By integrating the evidence from developmental biology, tumor biology and evolution, I will make a detailed discussion on the observations and propose that neural stemness underlies two coupled cell properties, tumorigenicity and pluripotent differentiation potential. Neural stemness property of tumorigenic cells can hopefully integrate different observations/concepts underlying tumorigenesis. Neural stem cells and tumorigenic cells share regulatory networks; both exhibit neural stemness, tumorigenicity and pluripotent differentiation potential; both depend on expression or activation of ancestral genes; both rely primarily on aerobic glycolytic metabolism; both can differentiate into various cells/tissues that are derived from three germ layers, leading to tumor formation resembling severely disorganized or more degenerated process of embryonic tissue differentiation; both are enriched in long genes with more splice variants that provide more plastic scaffolds for cell differentiation, etc. Neural regulatory networks, which include higher levels of basic machineries of cell physiological functions and developmental programs, work concertedly to define a basic state with fast cell cycle and proliferation. This is predestined by the evolutionary advantage of neural state, the ground or initial state for multicellularity with adaptation to an ancient environment. Tumorigenesis might represent a process of restoration of neural ground state, thereby restoring a state with fast proliferation and pluripotent differentiation potential in somatic cells. Tumorigenesis and pluripotent differentiation potential might be better understood from understanding neural stemness, and cancer therapy should benefit more from targeting neural stemness.}, } @article {pmid34711923, year = {2021}, author = {Wan, X and Saito, JA and Hou, S and Geib, SM and Yuryev, A and Higa, LM and Womersley, CZ and Alam, M}, title = {The Aphelenchus avenae genome highlights evolutionary adaptation to desiccation.}, journal = {Communications biology}, volume = {4}, number = {1}, pages = {1232}, pmid = {34711923}, issn = {2399-3642}, mesh = {Adaptation, Biological/*physiology ; Animals ; Biological Evolution ; *Desiccation ; Gene Duplication/physiology ; Gene Expression Profiling ; Helminth Proteins/*genetics/metabolism ; Humidity ; Phosphotransferases/*genetics/metabolism ; Tylenchida/enzymology/*genetics ; Water/*metabolism ; }, abstract = {Some organisms can withstand complete body water loss (losing up to 99% of body water) and stay in ametabolic state for decades until rehydration, which is known as anhydrobiosis. Few multicellular eukaryotes on their adult stage can withstand life without water. We still have an incomplete understanding of the mechanism for metazoan survival of anhydrobiosis. Here we report the 255-Mb genome of Aphelenchus avenae, which can endure relative zero humidity for years. Gene duplications arose genome-wide and contributed to the expansion and diversification of 763 kinases, which represents the second largest metazoan kinome to date. Transcriptome analyses of ametabolic state of A. avenae indicate the elevation of ATP level for global recycling of macromolecules and enhancement of autophagy in the early stage of anhydrobiosis. We catalogue 74 species-specific intrinsically disordered proteins, which may facilitate A. avenae to survive through desiccation stress. Our findings refine a molecular basis evolving for survival in extreme water loss and open the way for discovering new anti-desiccation strategies.}, } @article {pmid34699573, year = {2021}, author = {Tanno, A and Tokutsu, R and Arakaki, Y and Ueki, N and Minagawa, J and Yoshimura, K and Hisabori, T and Nozaki, H and Wakabayashi, KI}, title = {The four-celled Volvocales green alga Tetrabaena socialis exhibits weak photobehavior and high-photoprotection ability.}, journal = {PloS one}, volume = {16}, number = {10}, pages = {e0259138}, pmid = {34699573}, issn = {1932-6203}, mesh = {Chlorophyta/*physiology ; Photic Stimulation ; Phototropism/*physiology ; Volvox/*physiology ; }, abstract = {Photo-induced behavioral responses (photobehaviors) are crucial to the survival of motile phototrophic organisms in changing light conditions. Volvocine green algae are excellent model organisms for studying the regulatory mechanisms of photobehavior. We recently reported that unicellular Chlamydomonas reinhardtii and multicellular Volvox rousseletii exhibit similar photobehaviors, such as phototactic and photoshock responses, via different ciliary regulations. To clarify how the regulatory systems have changed during the evolution of multicellularity, we investigated the photobehaviors of four-celled Tetrabaena socialis. Surprisingly, unlike C. reinhardtii and V. rousseletii, T. socialis did not exhibit immediate photobehaviors after light illumination. Electrophysiological analysis revealed that the T. socialis eyespot does not function as a photoreceptor. Instead, T. socialis exhibited slow accumulation toward the light source in a photosynthesis-dependent manner. Our assessment of photosynthetic activities showed that T. socialis chloroplasts possess higher photoprotection abilities against strong light than C. reinhardtii. These data suggest that C. reinhardtii and T. socialis employ different strategies to avoid high-light stress (moving away rapidly and gaining photoprotection, respectively) despite their close phylogenetic relationship.}, } @article {pmid34695730, year = {2021}, author = {Grochau-Wright, ZI and Ferris, PJ and Tumberger, J and Jiménez-Marin, B and Olson, BJSC and Michod, RE}, title = {Characterization and Transformation of reg Cluster Genes in Volvox powersii Enable Investigation of Convergent Evolution of Cellular Differentiation in Volvox.}, journal = {Protist}, volume = {172}, number = {5-6}, pages = {125834}, doi = {10.1016/j.protis.2021.125834}, pmid = {34695730}, issn = {1618-0941}, support = {GT11065/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Base Sequence ; Cell Differentiation ; *Chlorophyta ; *Volvox/genetics ; }, abstract = {The evolution of germ-soma cellular differentiation represents a key step in the evolution of multicellular individuality. Volvox carteri and its relatives, the volvocine green algae, provide a model system for studying the evolution of cellular differentiation. In V. carteri, the regA gene controls somatic cell differentiation and is found in a group of paralogs called the reg cluster, along with rlsA, rlsB, and rlsC. However, the developmental program of V. carteri is derived compared to other volvocine algae. Here we examine Volvox powersii which possesses an ancestral developmental program and independent evolution of the Volvox body plan. We sequenced the reg cluster from V. powersii wild-type and a mutant with fewer cells and altered germ-soma ratio. We found that the mutant strain's rlsB gene has a deletion predicted to cause a truncated protein product. We developed a genetic transformation procedure to insert wild-type rlsB into the mutant strain. Transformation did not result in phenotypic rescue, suggesting the rlsB mutation is insufficient for generating the mutant phenotype. The transformation techniques and sequences described here provide essential tools to study V. powersii, a species well suited for studying the evolution of cellular differentiation and convergent evolution of Volvox morphology.}, } @article {pmid34685730, year = {2021}, author = {Ni, Z and Cheng, X}, title = {Origin and Isoform Specific Functions of Exchange Proteins Directly Activated by cAMP: A Phylogenetic Analysis.}, journal = {Cells}, volume = {10}, number = {10}, pages = {}, pmid = {34685730}, issn = {2073-4409}, support = {R35 GM122536/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Conserved Sequence ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Evolution, Molecular ; Guanine Nucleotide Exchange Factors/chemistry/*metabolism ; Humans ; *Phylogeny ; Protein Domains ; Protein Isoforms/chemistry/metabolism ; }, abstract = {Exchange proteins directly activated by cAMP (EPAC1 and EPAC2) are one of the several families of cellular effectors of the prototypical second messenger cAMP. To understand the origin and molecular evolution of EPAC proteins, we performed a comprehensive phylogenetic analysis of EPAC1 and EPAC2. Our study demonstrates that unlike its cousin PKA, EPAC proteins are only present in multicellular Metazoa. Within the EPAC family, EPAC1 is only associated with chordates, while EPAC2 spans the entire animal kingdom. Despite a much more contemporary origin, EPAC1 proteins show much more sequence diversity among species, suggesting that EPAC1 has undergone more selection and evolved faster than EPAC2. Phylogenetic analyses of the individual cAMP binding domain (CBD) and guanine nucleotide exchange (GEF) domain of EPACs, two most conserved regions between the two isoforms, further reveal that EPAC1 and EPAC2 are closely clustered together within both the larger cyclic nucleotide receptor and RAPGEF families. These results support the notion that EPAC1 and EPAC2 share a common ancestor resulting from a fusion between the CBD of PKA and the GEF from RAPGEF1. On the other hand, the two terminal extremities and the RAS-association (RA) domains show the most sequence diversity between the two isoforms. Sequence diversities within these regions contribute significantly to the isoform-specific functions of EPACs. Importantly, unique isoform-specific sequence motifs within the RA domain have been identified.}, } @article {pmid34681022, year = {2021}, author = {Luna, SK and Chain, FJJ}, title = {Lineage-Specific Genes and Family Expansions in Dictyostelid Genomes Display Expression Bias and Evolutionary Diversification during Development.}, journal = {Genes}, volume = {12}, number = {10}, pages = {}, pmid = {34681022}, issn = {2073-4425}, support = {R15 GM134498/GM/NIGMS NIH HHS/United States ; }, mesh = {Dictyostelium/*genetics/growth & development ; *Evolution, Molecular ; Gene Duplication/genetics ; Gene Expression Regulation, Developmental/genetics ; Genome/genetics ; *Phylogeny ; Species Specificity ; }, abstract = {Gene duplications generate new genes that can contribute to expression changes and the evolution of new functions. Genomes often consist of gene families that undergo expansions, some of which occur in specific lineages that reflect recent adaptive diversification. In this study, lineage-specific genes and gene family expansions were studied across five dictyostelid species to determine when and how they are expressed during multicellular development. Lineage-specific genes were found to be enriched among genes with biased expression (predominant expression in one developmental stage) in each species and at most developmental time points, suggesting independent functional innovations of new genes throughout the phylogeny. Biased duplicate genes had greater expression divergence than their orthologs and paralogs, consistent with subfunctionalization or neofunctionalization. Lineage-specific expansions in particular had biased genes with both molecular signals of positive selection and high expression, suggesting adaptive genetic and transcriptional diversification following duplication. Our results present insights into the potential contributions of lineage-specific genes and families in generating species-specific phenotypes during multicellular development in dictyostelids.}, } @article {pmid34680926, year = {2021}, author = {Cock, JM}, title = {Evolution of Multicellularity.}, journal = {Genes}, volume = {12}, number = {10}, pages = {}, pmid = {34680926}, issn = {2073-4425}, mesh = {Eukaryota/classification/cytology/genetics ; *Evolution, Molecular ; Phylogeny ; }, abstract = {The emergence of multicellular organisms was, perhaps, the most spectacular of the major transitions during the evolutionary history of life on this planet [...].}, } @article {pmid34671319, year = {2021}, author = {Quinting, T and Heymann, AK and Bicker, A and Nauth, T and Bernardini, A and Hankeln, T and Fandrey, J and Schreiber, T}, title = {Myoglobin Protects Breast Cancer Cells Due to Its ROS and NO Scavenging Properties.}, journal = {Frontiers in endocrinology}, volume = {12}, number = {}, pages = {732190}, pmid = {34671319}, issn = {1664-2392}, mesh = {Breast Neoplasms/genetics/metabolism/*pathology ; Cell Survival/drug effects/genetics ; Female ; Free Radical Scavengers/metabolism ; Gene Expression Regulation, Neoplastic/drug effects ; Gene Knockdown Techniques ; Humans ; Myoglobin/genetics/metabolism/*physiology ; Nitric Oxide/*metabolism ; Protective Agents/metabolism ; RNA, Small Interfering/pharmacology ; Reactive Oxygen Species/*metabolism ; Signal Transduction/drug effects/genetics ; Tumor Cells, Cultured ; }, abstract = {Myoglobin (MB) is an oxygen-binding protein usually found in cardiac myocytes and skeletal muscle fibers. It may function as a temporary storage and transport protein for O2 but could also have scavenging capacity for reactive oxygen and nitrogen species. In addition, MB has recently been identified as a hallmark in luminal breast cancer and was shown to be robustly induced under hypoxia. Cellular responses to hypoxia are regulated by the transcription factor hypoxia-inducible factor (HIF). For exploring the function of MB in breast cancer, we employed the human cell line MDA-MB-468. Cells were grown in monolayer or as 3D multicellular spheroids, which mimic the in vivo avascular tumor architecture and physiology with a heterogeneous cell population of proliferating cells in the rim and non-cycling or necrotic cells in the core region. This central necrosis was increased after MB knockdown, indicating a role for MB in hypoxic tumor regions. In addition, MB knockdown caused higher levels of HIF-1α protein after treatment with NO, which also plays an important role in cancer cell survival. MB knockdown also led to higher reactive oxygen species (ROS) levels in the cells after treatment with H2O2. To further explore the role of MB in cell survival, we performed RNA-Seq after MB knockdown and NO treatment. 1029 differentially expressed genes (DEGs), including 45 potential HIF-1 target genes, were annotated in regulatory pathways that modulate cellular function and maintenance, cell death and survival, and carbohydrate metabolism. Of these target genes, TMEFF1, TREX2, GLUT-1, MKNK-1, and RAB8B were significantly altered. Consistently, a decreased expression of GLUT-1, MKNK-1, and RAB8B after MB knockdown was confirmed by qPCR. All three genes of interest are often up regulated in cancer and correlate with a poor clinical outcome. Thus, our data indicate that myoglobin might influence the survival of breast cancer cells, possibly due to its ROS and NO scavenging properties and could be a valuable target for cancer therapy.}, } @article {pmid34665225, year = {2021}, author = {Zagoskin, MV and Wang, J}, title = {Programmed DNA elimination: silencing genes and repetitive sequences in somatic cells.}, journal = {Biochemical Society transactions}, volume = {49}, number = {5}, pages = {1891-1903}, pmid = {34665225}, issn = {1470-8752}, support = {R01 AI155588/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Chromosomes/genetics ; DNA Transposable Elements/*genetics ; Embryonic Development/genetics ; Evolution, Molecular ; Gene Expression ; Gene Expression Regulation ; *Gene Silencing ; Germ Cells ; Humans ; }, abstract = {In a multicellular organism, the genomes of all cells are in general the same. Programmed DNA elimination is a notable exception to this genome constancy rule. DNA elimination removes genes and repetitive elements in the germline genome to form a reduced somatic genome in various organisms. The process of DNA elimination within an organism is highly accurate and reproducible; it typically occurs during early embryogenesis, coincident with germline-soma differentiation. DNA elimination provides a mechanism to silence selected genes and repeats in somatic cells. Recent studies in nematodes suggest that DNA elimination removes all chromosome ends, resolves sex chromosome fusions, and may also promote the birth of novel genes. Programmed DNA elimination processes are diverse among species, suggesting DNA elimination likely has evolved multiple times in different taxa. The growing list of organisms that undergo DNA elimination indicates that DNA elimination may be more widespread than previously appreciated. These various organisms will serve as complementary and comparative models to study the function, mechanism, and evolution of programmed DNA elimination in metazoans.}, } @article {pmid34661335, year = {2022}, author = {Stüeken, EE and Viehmann, S and Hohl, SV}, title = {Contrasting nutrient availability between marine and brackish waters in the late Mesoproterozoic: Evidence from the Paranoá Group, Brazil.}, journal = {Geobiology}, volume = {20}, number = {2}, pages = {159-174}, doi = {10.1111/gbi.12478}, pmid = {34661335}, issn = {1472-4669}, mesh = {Brazil ; *Ecosystem ; Eukaryota ; Nutrients ; *Seawater ; }, abstract = {Understanding the delayed rise of eukaryotic life on Earth is one of the most fundamental questions about biological evolution. Numerous studies have presented evidence for oxygen and nutrient limitations in seawater during the Mesoproterozoic era, indicating that open marine settings may not have been able to sustain a eukaryotic biosphere with complex, multicellular organisms. However, many of these data sets represent restricted marine basins, which may bias our view of habitability. Furthermore, it remains untested whether rivers could have supplied significant nutrient fluxes to coastal habitats. To better characterize the sources of the major nutrients nitrogen and phosphorus, we turned to the late Mesoproterozoic Paranoá Group in Brazil (~1.1 Ga), which was deposited on a passive margin of the São Francisco craton. We present carbon, nitrogen and sulphur isotope data from an open shelf setting (Fazenda Funil) and from a brackish-water environment with significant riverine input (São Gabriel). Our results show that waters were well-oxygenated and nitrate was bioavailable in the open ocean setting at Fazenda Funil; the redoxcline appears to have been deeper and further offshore compared to restricted marine basins elsewhere in the Mesoproterozoic. In contrast, the brackish site at São Gabriel received only limited input of marine nitrate and sulphate. Nevertheless, previous reports of acritarchs reveal that this brackish-water setting was habitable to eukaryotic life. Paired with previously published cadmium isotope data, which can be used as a proxy for phosphorus cycling, our results suggest that complex organisms were perhaps not strictly dependent on marine nutrient supplies. Riverine influxes of P and possibly other nutrients likely rendered coastal waters perhaps equally habitable to the Mesoproterozoic open ocean. This conclusion supports the notion that eukaryotic organisms may have thrived in brackish or perhaps even freshwater environments.}, } @article {pmid34661162, year = {2021}, author = {Koya, J and Saito, Y and Kameda, T and Kogure, Y and Yuasa, M and Nagasaki, J and McClure, MB and Shingaki, S and Tabata, M and Tahira, Y and Akizuki, K and Kamiunten, A and Sekine, M and Shide, K and Kubuki, Y and Hidaka, T and Kitanaka, A and Nakano, N and Utsunomiya, A and Togashi, Y and Ogawa, S and Shimoda, K and Kataoka, K}, title = {Single-Cell Analysis of the Multicellular Ecosystem in Viral Carcinogenesis by HTLV-1.}, journal = {Blood cancer discovery}, volume = {2}, number = {5}, pages = {450-467}, pmid = {34661162}, issn = {2643-3249}, mesh = {Animals ; Carcinogenesis/genetics ; Ecosystem ; *Human T-lymphotropic virus 1/genetics ; *Leukemia-Lymphoma, Adult T-Cell/genetics ; Mice ; Single-Cell Analysis ; }, abstract = {UNLABELLED: Premalignant clonal expansion of human T-cell leukemia virus type-1 (HTLV-1)-infected cells occurs before viral carcinogenesis. Here we characterize premalignant cells and the multicellular ecosystem in HTLV-1 infection with and without adult T-cell leukemia/lymphoma (ATL) by genome sequencing and single-cell simultaneous transcriptome and T/B-cell receptor sequencing with surface protein analysis. We distinguish malignant phenotypes caused by HTLV-1 infection and leukemogenesis and dissect clonal evolution of malignant cells with different clinical behavior. Within HTLV-1-infected cells, a regulatory T-cell phenotype associates with premalignant clonal expansion. We also delineate differences between virus- and tumor-related changes in the nonmalignant hematopoietic pool, including tumor-specific myeloid propagation. In a newly generated conditional knockout mouse model recapitulating T-cell-restricted CD274 (encoding PD-L1) gene lesions found in ATL, we demonstrate that PD-L1 overexpressed by T cells is transferred to surrounding cells, leading to their PD-L1 upregulation. Our findings provide insights into clonal evolution and immune landscape of multistep virus carcinogenesis.

SIGNIFICANCE: Our multimodal single-cell analyses comprehensively dissect the cellular and molecular alterations of the peripheral blood in HTLV-1 infection, with and without progression to leukemia. This study not only sheds light on premalignant clonal expansion in viral carcinogenesis, but also helps to devise novel diagnostic and therapeutic strategies for HTLV-1-related disorders.}, } @article {pmid34648394, year = {2021}, author = {Simpson, C}, title = {Adaptation to a Viscous Snowball Earth Ocean as a Path to Complex Multicellularity.}, journal = {The American naturalist}, volume = {198}, number = {5}, pages = {590-609}, doi = {10.1086/716634}, pmid = {34648394}, issn = {1537-5323}, mesh = {Acclimatization ; Fungi ; *Ice Cover ; *Seawater ; Viscosity ; }, abstract = {AbstractAnimals, fungi, and algae with complex multicellular bodies all evolved independently from unicellular ancestors. The early history of these major eukaryotic multicellular clades, if not their origins, co-occur with an extreme phase of global glaciations known as the Snowball Earth. Here, I propose that the long-term loss of low-viscosity environments due to several rounds global glaciation drove the multiple origins of complex multicellularity in eukaryotes and the subsequent radiation of complex multicellular groups into previously unoccupied niches. In this scenario, life adapts to Snowball Earth oceans by evolving large size and faster speeds through multicellularity, which acts to compensate for high-viscosity seawater and achieve fluid flow at sufficient levels to satisfy metabolic needs. Warm, low-viscosity seawater returned with the melting of the Snowball glaciers, and with it, by virtue of large and fast multicellular bodies, new ways of life were unveiled.}, } @article {pmid34643506, year = {2021}, author = {Gao, Y and Park, HJ and Traulsen, A and Pichugin, Y}, title = {Evolution of irreversible somatic differentiation.}, journal = {eLife}, volume = {10}, number = {}, pages = {}, pmid = {34643506}, issn = {2050-084X}, mesh = {Animals ; *Biological Evolution ; *Cell Differentiation ; *Cell Division ; *Cell Lineage ; Gene Expression Regulation ; Germ Cells/*physiology ; *Models, Biological ; Phenotype ; }, abstract = {A key innovation emerging in complex animals is irreversible somatic differentiation: daughters of a vegetative cell perform a vegetative function as well, thus, forming a somatic lineage that can no longer be directly involved in reproduction. Primitive species use a different strategy: vegetative and reproductive tasks are separated in time rather than in space. Starting from such a strategy, how is it possible to evolve life forms which use some of their cells exclusively for vegetative functions? Here, we develop an evolutionary model of development of a simple multicellular organism and find that three components are necessary for the evolution of irreversible somatic differentiation: (i) costly cell differentiation, (ii) vegetative cells that significantly improve the organism's performance even if present in small numbers, and (iii) large enough organism size. Our findings demonstrate how an egalitarian development typical for loose cell colonies can evolve into germ-soma differentiation dominating metazoans.}, } @article {pmid34641578, year = {2021}, author = {Wofford, HA and Myers-Dean, J and Vogel, BA and Alamo, KAE and Longshore-Neate, FA and Jagodzinski, F and Amacher, JF}, title = {Domain Analysis and Motif Matcher (DAMM): A Program to Predict Selectivity Determinants in Monosiga brevicollis PDZ Domains Using Human PDZ Data.}, journal = {Molecules (Basel, Switzerland)}, volume = {26}, number = {19}, pages = {}, pmid = {34641578}, issn = {1420-3049}, mesh = {Amino Acid Sequence ; Choanoflagellata/*chemistry/*metabolism ; Computational Biology/*methods ; Evolution, Molecular ; Humans ; *PDZ Domains ; Phylogeny ; *Protein Binding ; Protein Conformation ; Signal Transduction ; Software ; Substrate Specificity ; }, abstract = {Choanoflagellates are single-celled eukaryotes with complex signaling pathways. They are considered the closest non-metazoan ancestors to mammals and other metazoans and form multicellular-like states called rosettes. The choanoflagellate Monosiga brevicollis contains over 150 PDZ domains, an important peptide-binding domain in all three domains of life (Archaea, Bacteria, and Eukarya). Therefore, an understanding of PDZ domain signaling pathways in choanoflagellates may provide insight into the origins of multicellularity. PDZ domains recognize the C-terminus of target proteins and regulate signaling and trafficking pathways, as well as cellular adhesion. Here, we developed a computational software suite, Domain Analysis and Motif Matcher (DAMM), that analyzes peptide-binding cleft sequence identity as compared with human PDZ domains and that can be used in combination with literature searches of known human PDZ-interacting sequences to predict target specificity in choanoflagellate PDZ domains. We used this program, protein biochemistry, fluorescence polarization, and structural analyses to characterize the specificity of A9UPE9_MONBE, a M. brevicollis PDZ domain-containing protein with no homology to any metazoan protein, finding that its PDZ domain is most similar to those of the DLG family. We then identified two endogenous sequences that bind A9UPE9 PDZ with <100 μM affinity, a value commonly considered the threshold for cellular PDZ-peptide interactions. Taken together, this approach can be used to predict cellular targets of previously uncharacterized PDZ domains in choanoflagellates and other organisms. Our data contribute to investigations into choanoflagellate signaling and how it informs metazoan evolution.}, } @article {pmid34639193, year = {2021}, author = {Siletsky, SA and Borisov, VB}, title = {Proton Pumping and Non-Pumping Terminal Respiratory Oxidases: Active Sites Intermediates of These Molecular Machines and Their Derivatives.}, journal = {International journal of molecular sciences}, volume = {22}, number = {19}, pages = {}, pmid = {34639193}, issn = {1422-0067}, mesh = {Catalysis ; Catalytic Domain ; Electron Transport ; Oxidoreductases/chemistry/*metabolism ; Proton Pumps/chemistry/*metabolism ; *Protons ; }, abstract = {Terminal respiratory oxidases are highly efficient molecular machines. These most important bioenergetic membrane enzymes transform the energy of chemical bonds released during the transfer of electrons along the respiratory chains of eukaryotes and prokaryotes from cytochromes or quinols to molecular oxygen into a transmembrane proton gradient. They participate in regulatory cascades and physiological anti-stress reactions in multicellular organisms. They also allow microorganisms to adapt to low-oxygen conditions, survive in chemically aggressive environments and acquire antibiotic resistance. To date, three-dimensional structures with atomic resolution of members of all major groups of terminal respiratory oxidases, heme-copper oxidases, and bd-type cytochromes, have been obtained. These groups of enzymes have different origins and a wide range of functional significance in cells. At the same time, all of them are united by a catalytic reaction of four-electron reduction in oxygen into water which proceeds without the formation and release of potentially dangerous ROS from active sites. The review analyzes recent structural and functional studies of oxygen reduction intermediates in the active sites of terminal respiratory oxidases, the features of catalytic cycles, and the properties of the active sites of these enzymes.}, } @article {pmid34635955, year = {2021}, author = {Schneider, C}, title = {Tuft cell integration of luminal states and interaction modules in tissues.}, journal = {Pflugers Archiv : European journal of physiology}, volume = {473}, number = {11}, pages = {1713-1722}, pmid = {34635955}, issn = {1432-2013}, mesh = {Animals ; Chemoreceptor Cells/*physiology ; Epithelial Cells/*physiology ; Humans ; Immunity, Innate/physiology ; }, abstract = {Chemosensory processes are integral to the physiology of most organisms. This function is typically performed by specialized cells that are able to detect input signals and to convert them to an output dedicated to a particular group of target cells. Tuft cells are cholinergic chemosensory epithelial cells capable of producing immunologically relevant effector molecules. They are scattered throughout endoderm-derived hollow organs and function as sensors of luminal stimuli, which has been best studied in mucosal barrier epithelia. Given their epithelial origin and broad distribution, and based on their interplay with immune pathways, tuft cells can be considered a prototypical example of how complex multicellular organisms engage innate immune mechanisms to modulate and optimize organ physiology. In this review, I provide a concise overview of tuft cells and discuss how these cells influence organ adaptation to dynamic luminal conditions.}, } @article {pmid34628994, year = {2021}, author = {Caetano-Anollés, G and Aziz, MF and Mughal, F and Caetano-Anollés, D}, title = {Tracing protein and proteome history with chronologies and networks: folding recapitulates evolution.}, journal = {Expert review of proteomics}, volume = {18}, number = {10}, pages = {863-880}, doi = {10.1080/14789450.2021.1992277}, pmid = {34628994}, issn = {1744-8387}, mesh = {*Evolution, Molecular ; Genomics ; Humans ; Phylogeny ; Protein Folding ; *Proteome/genetics ; }, abstract = {INTRODUCTION: While the origin and evolution of proteins remain mysterious, advances in evolutionary genomics and systems biology are facilitating the historical exploration of the structure, function and organization of proteins and proteomes. Molecular chronologies are series of time events describing the history of biological systems and subsystems and the rise of biological innovations. Together with time-varying networks, these chronologies provide a window into the past.

AREAS COVERED: Here, we review molecular chronologies and networks built with modern methods of phylogeny reconstruction. We discuss how chronologies of structural domain families uncover the explosive emergence of metabolism, the late rise of translation, the co-evolution of ribosomal proteins and rRNA, and the late development of the ribosomal exit tunnel; events that coincided with a tendency to shorten folding time. Evolving networks described the early emergence of domains and a late 'big bang' of domain combinations.

EXPERT OPINION: Two processes, folding and recruitment appear central to the evolutionary progression. The former increases protein persistence. The later fosters diversity. Chronologically, protein evolution mirrors folding by combining supersecondary structures into domains, developing translation machinery to facilitate folding speed and stability, and enhancing structural complexity by establishing long-distance interactions in novel structural and architectural designs.}, } @article {pmid34596678, year = {2021}, author = {Schiller, EA and Bergstralh, DT}, title = {Interaction between Discs large and Pins/LGN/GPSM2: a comparison across species.}, journal = {Biology open}, volume = {10}, number = {11}, pages = {}, pmid = {34596678}, issn = {2046-6390}, support = {R01 GM125839/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Batrachoidiformes/genetics ; Caenorhabditis elegans/genetics ; Caenorhabditis elegans Proteins/metabolism ; Carrier Proteins/*metabolism ; Cell Cycle Proteins/*metabolism ; Cell Division/*genetics ; Cnidaria/genetics ; Drosophila Proteins/metabolism ; Guanylate Kinases/metabolism ; Phylogeny ; Spindle Apparatus/*metabolism ; }, abstract = {The orientation of the mitotic spindle determines the direction of cell division, and therefore contributes to tissue shape and cell fate. Interaction between the multifunctional scaffolding protein Discs large (Dlg) and the canonical spindle orienting factor GPSM2 (called Pins in Drosophila and LGN in vertebrates) has been established in bilaterian models, but its function remains unclear. We used a phylogenetic approach to test whether the interaction is obligate in animals, and in particular whether Pins/LGN/GPSM2 evolved in multicellular organisms as a Dlg-binding protein. We show that Dlg diverged in C. elegans and the syncytial sponge Opsacas minuta and propose that this divergence may correspond with differences in spindle orientation requirements between these organisms and the canonical pathways described in bilaterians. We also demonstrate that Pins/LGN/GPSM2 is present in basal animals, but the established Dlg-interaction site cannot be found in either Placozoa or Porifera. Our results suggest that the interaction between Pins/LGN/GPSM2 and Dlg appeared in Cnidaria, and we therefore speculate that it may have evolved to promote accurate division orientation in the nervous system. This work reveals the evolutionary history of the Pins/LGN/GPSM2-Dlg interaction and suggests new possibilities for its importance in spindle orientation during epithelial and neural tissue development.}, } @article {pmid34592312, year = {2021}, author = {Shrestha, S and Clark, AC}, title = {Evolution of the folding landscape of effector caspases.}, journal = {The Journal of biological chemistry}, volume = {297}, number = {5}, pages = {101249}, pmid = {34592312}, issn = {1083-351X}, support = {R01 GM127654/GM/NIGMS NIH HHS/United States ; }, mesh = {Caspases, Effector/*chemistry/genetics/metabolism ; *Evolution, Molecular ; Humans ; *Models, Molecular ; *Protein Folding ; *Protein Multimerization ; }, abstract = {Caspases are a family of cysteinyl proteases that control programmed cell death and maintain homeostasis in multicellular organisms. The caspase family is an excellent model to study protein evolution because all caspases are produced as zymogens (procaspases [PCPs]) that must be activated to gain full activity; the protein structures are conserved through hundreds of millions of years of evolution; and some allosteric features arose with the early ancestor, whereas others are more recent evolutionary events. The apoptotic caspases evolved from a common ancestor (CA) into two distinct subfamilies: monomers (initiator caspases) or dimers (effector caspases). Differences in activation mechanisms of the two subfamilies, and their oligomeric forms, play a central role in the regulation of apoptosis. Here, we examine changes in the folding landscape by characterizing human effector caspases and their CA. The results show that the effector caspases unfold by a minimum three-state equilibrium model at pH 7.5, where the native dimer is in equilibrium with a partially folded monomeric (PCP-7, CA) or dimeric (PCP-6) intermediate. In comparison, the unfolding pathway of PCP-3 contains both oligomeric forms of the intermediate. Overall, the data show that the folding landscape was first established with the CA and was retained for >650 million years. Partially folded monomeric or dimeric intermediates in the ancestral ensemble provide mechanisms for evolutionary changes that affect stability of extant caspases. The conserved folding landscape allows for the fine-tuning of enzyme stability in a species-dependent manner while retaining the overall caspase-hemoglobinase fold.}, } @article {pmid34592264, year = {2022}, author = {Sego, TJ and Mochan, ED and Ermentrout, GB and Glazier, JA}, title = {A multiscale multicellular spatiotemporal model of local influenza infection and immune response.}, journal = {Journal of theoretical biology}, volume = {532}, number = {}, pages = {110918}, pmid = {34592264}, issn = {1095-8541}, support = {U24 EB028887/EB/NIBIB NIH HHS/United States ; R01 GM122424/GM/NIGMS NIH HHS/United States ; }, mesh = {*COVID-19 ; Humans ; Immunity, Innate ; *Influenza, Human ; SARS-CoV-2 ; *Virus Diseases ; }, abstract = {Respiratory viral infections pose a serious public health concern, from mild seasonal influenza to pandemics like those of SARS-CoV-2. Spatiotemporal dynamics of viral infection impact nearly all aspects of the progression of a viral infection, like the dependence of viral replication rates on the type of cell and pathogen, the strength of the immune response and localization of infection. Mathematical modeling is often used to describe respiratory viral infections and the immune response to them using ordinary differential equation (ODE) models. However, ODE models neglect spatially-resolved biophysical mechanisms like lesion shape and the details of viral transport, and so cannot model spatial effects of a viral infection and immune response. In this work, we develop a multiscale, multicellular spatiotemporal model of influenza infection and immune response by combining non-spatial ODE modeling and spatial, cell-based modeling. We employ cellularization, a recently developed method for generating spatial, cell-based, stochastic models from non-spatial ODE models, to generate much of our model from a calibrated ODE model that describes infection, death and recovery of susceptible cells and innate and adaptive responses during influenza infection, and develop models of cell migration and other mechanisms not explicitly described by the ODE model. We determine new model parameters to generate agreement between the spatial and original ODE models under certain conditions, where simulation replicas using our model serve as microconfigurations of the ODE model, and compare results between the models to investigate the nature of viral exposure and impact of heterogeneous infection on the time-evolution of the viral infection. We found that using spatially homogeneous initial exposure conditions consistently with those employed during calibration of the ODE model generates far less severe infection, and that local exposure to virus must be multiple orders of magnitude greater than a uniformly applied exposure to all available susceptible cells. This strongly suggests a prominent role of localization of exposure in influenza A infection. We propose that the particularities of the microenvironment to which a virus is introduced plays a dominant role in disease onset and progression, and that spatially resolved models like ours may be important to better understand and more reliably predict future health states based on susceptibility of potential lesion sites using spatially resolved patient data of the state of an infection. We can readily integrate the immune response components of our model into other modeling and simulation frameworks of viral infection dynamics that do detailed modeling of other mechanisms like viral internalization and intracellular viral replication dynamics, which are not explicitly represented in the ODE model. We can also combine our model with available experimental data and modeling of exposure scenarios and spatiotemporal aspects of mechanisms like mucociliary clearance that are only implicitly described by the ODE model, which would significantly improve the ability of our model to present spatially resolved predictions about the progression of influenza infection and immune response.}, } @article {pmid34571874, year = {2021}, author = {Buravkova, L and Larina, I and Andreeva, E and Grigoriev, A}, title = {Microgravity Effects on the Matrisome.}, journal = {Cells}, volume = {10}, number = {9}, pages = {}, pmid = {34571874}, issn = {2073-4409}, mesh = {Animals ; Extracellular Matrix/*physiology ; Gravity, Altered ; Humans ; Space Flight/methods ; Weightlessness ; }, abstract = {Gravity is fundamental factor determining all processes of development and vital activity on Earth. During evolution, a complex mechanism of response to gravity alterations was formed in multicellular organisms. It includes the "gravisensors" in extracellular and intracellular spaces. Inside the cells, the cytoskeleton molecules are the principal gravity-sensitive structures, and outside the cells these are extracellular matrix (ECM) components. The cooperation between the intracellular and extracellular compartments is implemented through specialized protein structures, integrins. The gravity-sensitive complex is a kind of molecular hub that coordinates the functions of various tissues and organs in the gravitational environment. The functioning of this system is of particular importance under extremal conditions, such as spaceflight microgravity. This review covers the current understanding of ECM and associated molecules as the matrisome, the features of the above components in connective tissues, and the role of the latter in the cell and tissue responses to the gravity alterations. Special attention is paid to contemporary methodological approaches to the matrisome composition analysis under real space flights and ground-based simulation of its effects on Earth.}, } @article {pmid34564856, year = {2021}, author = {Charles Campbell, F}, title = {Untangling the complexities of micropapillary cancer[†].}, journal = {The Journal of pathology}, volume = {255}, number = {4}, pages = {343-345}, doi = {10.1002/path.5809}, pmid = {34564856}, issn = {1096-9896}, support = {C9136/A15342/CRUK_/Cancer Research UK/United Kingdom ; MR/L015110/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*Adenocarcinoma of Lung ; *Carcinoma, Papillary ; Cell Polarity ; *Colorectal Neoplasms ; Humans ; *Lung Neoplasms ; }, abstract = {Distinct morphological subtypes of colorectal cancer (CRC) confer a bleak clinical outlook. In a recent issue of The Journal of Pathology, Onuma et al investigated morphological evolution of a highly fatal CRC subtype known as micropapillary cancer (MPC). This study enhances understanding of MPC biology including essential regulatory signals, cellular and multicellular phenotypes, as well as cancer behaviour. Iterative modelling in three-dimensional (3D) patient-derived CRC tissue-originated spheroids (CTOSs) revealed spatiotemporal oscillations of Rho-ROCK hyperactivity underlying reversal of membrane polarity and suppression of lumen formation during development of multicellular MPC morphology. Corroborative studies in CTOSs, xenografts, and archival human CRCs confirm human disease relevance. Although cancer morphology has previously been considered irreversible, targeted inhibition of Rho-ROCK activity restored membrane polarity, lumenized multicellular assembly, and suppressed MPC morphology in 3D CTOS cultures and xenografts. Collectively, the study identifies molecular, biophysical, and multicellular mechanisms implicated in morphological evolution of micropapillary CRC. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.}, } @article {pmid34556094, year = {2021}, author = {Krishna, A and Gardiner, J and Donner, TJ and Scarpella, E}, title = {Control of vein-forming, striped gene expression by auxin signaling.}, journal = {BMC biology}, volume = {19}, number = {1}, pages = {213}, pmid = {34556094}, issn = {1741-7007}, mesh = {*Arabidopsis/genetics/metabolism ; Arabidopsis Proteins/genetics/metabolism ; Gene Expression ; Gene Expression Regulation, Plant ; Indoleacetic Acids ; Transcription Factors/genetics/metabolism ; }, abstract = {BACKGROUND: Activation of gene expression in striped domains is a key building block of biological patterning, from the recursive formation of veins in plant leaves to that of ribs and vertebrae in our bodies. In animals, gene expression is activated in striped domains by the differential affinity of broadly expressed transcription factors for their target genes and the combinatorial interaction between such target genes. In plants, how gene expression is activated in striped domains is instead unknown. We address this question for the broadly expressed MONOPTEROS (MP) transcription factor and its target gene ARABIDOPSIS THALIANA HOMEOBOX FACTOR8 (ATHB8).

RESULTS: We find that ATHB8 promotes vein formation and that such vein-forming function depends on both levels of ATHB8 expression and width of ATHB8 expression domains. We further find that ATHB8 expression is activated in striped domains by a combination of (1) activation of ATHB8 expression through binding of peak levels of MP to a low-affinity MP-binding site in the ATHB8 promoter and (2) repression of ATHB8 expression by MP target genes of the AUXIN/INDOLE-3-ACETIC-ACID-INDUCIBLE family.

CONCLUSIONS: Our findings suggest that a common regulatory logic controls activation of gene expression in striped domains in both plants and animals despite the independent evolution of their multicellularity.}, } @article {pmid34547424, year = {2021}, author = {Kun, Á}, title = {The major evolutionary transitions and codes of life.}, journal = {Bio Systems}, volume = {210}, number = {}, pages = {104548}, doi = {10.1016/j.biosystems.2021.104548}, pmid = {34547424}, issn = {1872-8324}, mesh = {Animals ; *Biological Evolution ; Genetic Code/*genetics ; Humans ; Organelles/*physiology ; *Origin of Life ; Spheroids, Cellular/physiology ; }, abstract = {Major evolutionary transitions as well as the evolution of codes of life are key elements in macroevolution which are characterized by increase in complexity Major evolutionary transitions ensues by a transition in individuality and by the evolution of a novel mode of using, transmitting or storing information. Here is where codes of life enter the picture: they are arbitrary mappings between different (mostly) molecular species. This flexibility allows information to be employed in a variety of ways, which can fuel evolutionary innovation. The collation of the list of major evolutionary transitions and the list of codes of life show a clear pattern: codes evolved prior to a major evolutionary transition and then played roles in the transition and/or in the transformation of the new individual. The evolution of a new code of life is in itself not a major evolutionary transition but allow major evolutionary transitions to happen. This could help us to identify new organic codes.}, } @article {pmid34546795, year = {2021}, author = {Umen, J and Herron, MD}, title = {Green Algal Models for Multicellularity.}, journal = {Annual review of genetics}, volume = {55}, number = {}, pages = {603-632}, doi = {10.1146/annurev-genet-032321-091533}, pmid = {34546795}, issn = {1545-2948}, support = {R01 GM126557/GM/NIGMS NIH HHS/United States ; }, mesh = {Biological Evolution ; *Chlorophyta/genetics ; Genome ; Phylogeny ; *Volvox/genetics ; }, abstract = {The repeated evolution of multicellularity across the tree of life has profoundly affected the ecology and evolution of nearly all life on Earth. Many of these origins were in different groups of photosynthetic eukaryotes, or algae. Here, we review the evolution and genetics of multicellularity in several groups of green algae, which include the closest relatives of land plants. These include millimeter-scale, motile spheroids of up to 50,000 cells in the volvocine algae; decimeter-scale seaweeds in the genus Ulva (sea lettuce); and very plantlike, meter-scale freshwater algae in the genus Chara (stoneworts). We also describe algae in the genus Caulerpa, which are giant, multinucleate, morphologically complex single cells. In each case, we review the life cycle, phylogeny, and genetics of traits relevant to the evolution of multicellularity, and genetic and genomic resources available for the group in question. Finally, we suggest routes toward developing these groups as model organisms for the evolution of multicellularity.}, } @article {pmid34545570, year = {2021}, author = {Maryenti, T and Ishii, T and Okamoto, T}, title = {Development and regeneration of wheat-rice hybrid zygotes produced by in vitro fertilization system.}, journal = {The New phytologist}, volume = {232}, number = {6}, pages = {2369-2383}, pmid = {34545570}, issn = {1469-8137}, mesh = {Fertilization in Vitro ; *Oryza/genetics ; Seeds/genetics ; Triticum/genetics ; *Zygote ; }, abstract = {Hybridization plays a decisive role in the evolution and diversification of angiosperms. However, the mechanisms of wide hybridization remain open because pre- and post-fertilization barriers limit the production and development of inter-subfamily/intergeneric zygotes, respectively. We examined hybridization between wheat and rice using an in vitro fertilization (IVF) system to bypass these barriers. Several gamete combinations of allopolyploid wheat-rice hybrid zygotes were successfully produced, and the developmental profiles of hybrid zygotes were analyzed. Hybrid zygotes derived from one rice egg cell and one wheat sperm cell ceased at the multicellular embryo-like structure stage. This developmental barrier was overcome by adding one wheat egg cell to the wheat-rice hybrid zygote. In the reciprocal combination, one wheat egg and one rice sperm cell, the resulting hybrid zygotes failed to divide. However, doubling the dosage of rice sperm cell allowed the hybrid zygotes to develop into plantlets. Rice chromosomes appeared to be progressively eliminated during the early developmental stage of these hybrid embryos, and c. 20% of regenerated plants showed abnormal morphology. These results suggest that hybrid breakdown can be overcome through optimization of gamete combinations, and the present hybrid will provide a new horizon for utilization of inter-subfamily genetic resources.}, } @article {pmid34529461, year = {2021}, author = {Leslie, AB and Simpson, C and Mander, L}, title = {Reproductive innovations and pulsed rise in plant complexity.}, journal = {Science (New York, N.Y.)}, volume = {373}, number = {6561}, pages = {1368-1372}, doi = {10.1126/science.abi6984}, pmid = {34529461}, issn = {1095-9203}, mesh = {*Biological Evolution ; Cycadopsida/anatomy & histology/genetics/growth & development ; Embryophyta/*anatomy & histology/growth & development/physiology ; Flowers/*anatomy & histology ; Fossils ; Magnoliopsida/anatomy & histology/genetics/growth & development/physiology ; Plant Structures/*anatomy & histology/growth & development ; Pollination ; Reproduction ; *Seeds ; Sporangia/anatomy & histology ; }, abstract = {Morphological complexity is a notable feature of multicellular life, although whether it evolves gradually or in early bursts is unclear. Vascular plant reproductive structures, such as flowers, are familiar examples of complex morphology. In this study, we use a simple approach based on the number of part types to analyze changes in complexity over time. We find that reproductive complexity increased in two pulses separated by ~250 million years of stasis, including an initial rise in the Devonian with the radiation of vascular plants and a pronounced increase in the Late Cretaceous that reflects flowering plant diversification. These pulses are associated with innovations that increased functional diversity, suggesting that shifts in complexity are linked to changes in function regardless of whether they occur early or late in the history of vascular plants.}, } @article {pmid34525330, year = {2021}, author = {Martinez-Miguel, VE and Lujan, C and Espie-Caullet, T and Martinez-Martinez, D and Moore, S and Backes, C and Gonzalez, S and Galimov, ER and Brown, AEX and Halic, M and Tomita, K and Rallis, C and von der Haar, T and Cabreiro, F and Bjedov, I}, title = {Increased fidelity of protein synthesis extends lifespan.}, journal = {Cell metabolism}, volume = {33}, number = {11}, pages = {2288-2300.e12}, pmid = {34525330}, issn = {1932-7420}, support = {R01 GM135599/GM/NIGMS NIH HHS/United States ; C416/A25145/CRUK_/Cancer Research UK/United Kingdom ; C7893/A28990/CRUK_/Cancer Research UK/United Kingdom ; MC_UP_1605/6/MRC_/Medical Research Council/United Kingdom ; 201487/WT_/Wellcome Trust/United Kingdom ; 102532/Z/12/Z/WT_/Wellcome Trust/United Kingdom ; BB/V006916/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; 102531/Z/13/A/WT_/Wellcome Trust/United Kingdom ; MR/M02492X/1/MRC_/Medical Research Council/United Kingdom ; MC-A654-5QC80/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; }, mesh = {*Longevity/genetics ; Phylogeny ; Protein Biosynthesis ; *Proteostasis/genetics ; Saccharomyces cerevisiae/genetics ; }, abstract = {Loss of proteostasis is a fundamental process driving aging. Proteostasis is affected by the accuracy of translation, yet the physiological consequence of having fewer protein synthesis errors during multi-cellular organismal aging is poorly understood. Our phylogenetic analysis of RPS23, a key protein in the ribosomal decoding center, uncovered a lysine residue almost universally conserved across all domains of life, which is replaced by an arginine in a small number of hyperthermophilic archaea. When introduced into eukaryotic RPS23 homologs, this mutation leads to accurate translation, as well as heat shock resistance and longer life, in yeast, worms, and flies. Furthermore, we show that anti-aging drugs such as rapamycin, Torin1, and trametinib reduce translation errors, and that rapamycin extends further organismal longevity in RPS23 hyperaccuracy mutants. This implies a unified mode of action for diverse pharmacological anti-aging therapies. These findings pave the way for identifying novel translation accuracy interventions to improve aging.}, } @article {pmid34521896, year = {2021}, author = {Elsner, D and Hartfelder, K and Korb, J}, title = {Molecular underpinnings of division of labour among workers in a socially complex termite.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {18269}, pmid = {34521896}, issn = {2045-2322}, mesh = {Animals ; Biological Evolution ; *Evolution, Molecular ; Female ; Gene Expression ; Gene Expression Profiling ; Genes, Insect/genetics ; Isoptera/*genetics/physiology ; Male ; *Social Behavior ; Transcriptome/genetics ; }, abstract = {Division of labour characterizes all major evolutionary transitions, such as the evolution of eukaryotic cells or multicellular organisms. Social insects are characterized by reproductive division of labour, with one or a few reproducing individuals (queens) and many non-reproducing nestmates (workers) forming a colony. Among the workers, further division of labour can occur with different individuals performing different tasks such as foraging, brood care or building. While mechanisms underlying task division are intensively studied in social Hymenoptera, less is known for termites, which independently evolved eusociality. We investigated molecular mechanisms underlying task division in termite workers to test for communality with social Hymenoptera. We compared similar-aged foraging workers with builders of the fungus-growing termite Macrotermes bellicosus using transcriptomes, endocrine measures and estimators of physiological condition. Based on results for social Hymenoptera and theory, we tested the hypotheses that (i) foragers are in worse physiological conditions than builders, (ii) builders are more similar in their gene expression profile to queens than foragers are, and (iii) builders invest more in anti-ageing mechanism than foragers. Our results support all three hypotheses. We found storage proteins to underlie task division of these similar-aged termite workers and these genes also characterize reproductive division of labour between queens and workers. This implies a co-option of nutrient-based pathways to regulate division of labour across lineages of termites and social Hymenoptera, which are separated by more than 133 million years.}, } @article {pmid34520764, year = {2021}, author = {Steventon, B and Busby, L and Arias, AM}, title = {Establishment of the vertebrate body plan: Rethinking gastrulation through stem cell models of early embryogenesis.}, journal = {Developmental cell}, volume = {56}, number = {17}, pages = {2405-2418}, doi = {10.1016/j.devcel.2021.08.012}, pmid = {34520764}, issn = {1878-1551}, support = {109408/Z/15/Z/WT_/Wellcome Trust/United Kingdom ; /BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Embryonic Development/genetics/*physiology ; Gastrulation/*physiology ; Gene Expression Regulation, Developmental/genetics/physiology ; Humans ; Morphogenesis/*physiology ; Stem Cells/*cytology ; Vertebrates/genetics ; }, abstract = {A striking property of vertebrate embryos is the emergence of a conserved body plan across a wide range of organisms through the process of gastrulation. As the body plan unfolds, gene regulatory networks (GRNs) and multicellular interactions (cell regulatory networks, CRNs) combine to generate a conserved set of morphogenetic events that lead to the phylotypic stage. Interrogation of these multilevel interactions requires manipulation of the mechanical environment, which is difficult in vivo. We review recent studies of stem cell models of early embryogenesis from different species showing that, independent of species origin, cells in culture form similar structures. The main difference between embryos and in vitro models is the boundary conditions of the multicellular ensembles. We discuss these observations and suggest that the mechanical and geometric boundary conditions of different embryos before gastrulation hide a morphogenetic ground state that is revealed in the stem-cell-based models of embryo development.}, } @article {pmid34516543, year = {2021}, author = {Henriques, GJB and van Vliet, S and Doebeli, M}, title = {Multilevel selection favors fragmentation modes that maintain cooperative interactions in multispecies communities.}, journal = {PLoS computational biology}, volume = {17}, number = {9}, pages = {e1008896}, pmid = {34516543}, issn = {1553-7358}, mesh = {*Models, Biological ; Mutation ; Plants/classification/genetics ; Reproduction/genetics ; *Selection, Genetic ; Species Specificity ; }, abstract = {Reproduction is one of the requirements for evolution and a defining feature of life. Yet, across the tree of life, organisms reproduce in many different ways. Groups of cells (e.g., multicellular organisms, colonial microbes, or multispecies biofilms) divide by releasing propagules that can be single-celled or multicellular. What conditions determine the number and size of reproductive propagules? In multicellular organisms, existing theory suggests that single-cell propagules prevent the accumulation of deleterious mutations (e.g., cheaters). However, groups of cells, such as biofilms, sometimes contain multiple metabolically interdependent species. This creates a reproductive dilemma: small daughter groups, which prevent the accumulation of cheaters, are also unlikely to contain the species diversity that is required for ecological success. Here, we developed an individual-based, multilevel selection model to investigate how such multi-species groups can resolve this dilemma. By tracking the dynamics of groups of cells that reproduce by fragmenting into smaller groups, we identified fragmentation modes that can maintain cooperative interactions. We systematically varied the fragmentation mode and calculated the maximum mutation rate that communities can withstand before being driven to extinction by the accumulation of cheaters. We find that for groups consisting of a single species, the optimal fragmentation mode consists of releasing single-cell propagules. For multi-species groups we find various optimal strategies. With migration between groups, single-cell propagules are favored. Without migration, larger propagules sizes are optimal; in this case, group-size dependent fissioning rates can prevent the accumulation of cheaters. Our work shows that multi-species groups can evolve reproductive strategies that allow them to maintain cooperative interactions.}, } @article {pmid34486115, year = {2021}, author = {Roy, SW}, title = {Digest: Three sexes from two loci in one genome: A haploid alga expands the diversity of trioecious species.}, journal = {Evolution; international journal of organic evolution}, volume = {75}, number = {11}, pages = {3002-3003}, doi = {10.1111/evo.14345}, pmid = {34486115}, issn = {1558-5646}, mesh = {Female ; *Genome ; Haploidy ; Humans ; Male ; }, abstract = {Multicellular eukaryotes exhibit a remarkable diversity of sexual systems; however, trioecy, the coexistence of male, female, and cosexual or hermaphrodite individuals in a single species, is remarkably rare. Takahashi et al. (2021) report the first known instance of trioecy in a haploid organism. In contrast to other known cases of trioecy, the authors report evidence for genetic control of all three sexes by two loci. These results complicate models for sexual system turnover and expand the known diversity of trioecy species in several ways.}, } @article {pmid34477897, year = {2021}, author = {Swiatczak, B}, title = {Struggle within: evolution and ecology of somatic cell populations.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {78}, number = {21-22}, pages = {6797-6806}, pmid = {34477897}, issn = {1420-9071}, mesh = {Adaptive Immunity/genetics ; Animals ; Biological Evolution ; DNA/genetics ; Ecology ; Humans ; Mutation/*genetics ; Selection, Genetic/genetics ; }, abstract = {The extent to which normal (nonmalignant) cells of the body can evolve through mutation and selection during the lifetime of the organism has been a major unresolved issue in evolutionary and developmental studies. On the one hand, stable multicellular individuality seems to depend on genetic homogeneity and suppression of evolutionary conflicts at the cellular level. On the other hand, the example of clonal selection of lymphocytes indicates that certain forms of somatic mutation and selection are concordant with the organism-level fitness. Recent DNA sequencing and tissue physiology studies suggest that in addition to adaptive immune cells also neurons, epithelial cells, epidermal cells, hematopoietic stem cells and functional cells in solid bodily organs are subject to evolutionary forces during the lifetime of an organism. Here we refer to these recent studies and suggest that the expanding list of somatically evolving cells modifies idealized views of biological individuals as radically different from collectives.}, } @article {pmid34476388, year = {2021}, author = {Boedicker, JQ and Gangan, M and Naughton, K and Zhao, F and Gralnick, JA and El-Naggar, MY}, title = {Engineering Biological Electron Transfer and Redox Pathways for Nanoparticle Synthesis.}, journal = {Bioelectricity}, volume = {3}, number = {2}, pages = {126-135}, pmid = {34476388}, issn = {2576-3113}, abstract = {Many species of bacteria are naturally capable of types of electron transport not observed in eukaryotic cells. Some species live in environments containing heavy metals not typically encountered by cells of multicellular organisms, such as arsenic, cadmium, and mercury, leading to the evolution of enzymes to deal with these environmental toxins. Bacteria also inhabit a variety of extreme environments, and are capable of respiration even in the absence of oxygen as a terminal electron acceptor. Over the years, several of these exotic redox and electron transport pathways have been discovered and characterized in molecular-level detail, and more recently synthetic biology has begun to utilize these pathways to engineer cells capable of detecting and processing a variety of metals and semimetals. One such application is the biologically controlled synthesis of nanoparticles. This review will introduce the basic concepts of bacterial metal reduction, summarize recent work in engineering bacteria for nanoparticle production, and highlight the most cutting-edge work in the characterization and application of bacterial electron transport pathways.}, } @article {pmid34467433, year = {2021}, author = {Wang, X and Dong, F and Liu, J and Tan, Y and Hu, S and Zhao, H}, title = {The self-healing of Bacillus subtilis biofilms.}, journal = {Archives of microbiology}, volume = {203}, number = {9}, pages = {5635-5645}, pmid = {34467433}, issn = {1432-072X}, mesh = {*Bacillus subtilis ; *Biofilms ; Humans ; }, abstract = {Self-healing is an intrinsic ability that exists widely in every multicellular biological organism. Our recent experiments have shown that bacterial biofilms also have the ability to self-heal after man-make cuts, but the mechanism of biofilm self-healing have not been studied. We find that the healing process of cuts on the biofilm depends on cut geometries like its location or direction, the biofilm itself like the biofilm age, the growing substrate properties like its hardness, and also the environments such as the competitive growth of multiple biofilms. What is more, the healing rate along the cut is heterogeneous, and the maximum healing rate can reach 260 μm/h, which is three times the undestroyed biofilm expansion rate. The cut does not change the rounded shape growth of biofilms. Further study of phenotypic evolution shows that the cut delays bacterial differentiation; motile cells perceive the cut and move to the cut area, while the cut only heals when there are enough matrix-producing cells in the cut area. Our work suggests new ideas for developing self-healing materials.}, } @article {pmid34465312, year = {2021}, author = {Lindsey, CR and Rosenzweig, F and Herron, MD}, title = {Phylotranscriptomics points to multiple independent origins of multicellularity and cellular differentiation in the volvocine algae.}, journal = {BMC biology}, volume = {19}, number = {1}, pages = {182}, pmid = {34465312}, issn = {1741-7007}, mesh = {Bayes Theorem ; Biological Evolution ; Cell Differentiation ; Chlamydomonas reinhardtii ; *Phylogeny ; Transcriptome ; Volvox/genetics ; }, abstract = {BACKGROUND: The volvocine algae, which include the single-celled species Chlamydomonas reinhardtii and the colonial species Volvox carteri, serve as a model in which to study the evolution of multicellularity and cellular differentiation. Studies reconstructing the history of this group have by and large relied on datasets of one to a few genes for phylogenetic inference and ancestral character state reconstruction. As a result, volvocine phylogenies lack concordance depending on the number and/or type of genes (i.e., chloroplast vs nuclear) chosen for phylogenetic inference. While multiple studies suggest that multicellularity evolved only once in the volvocine algae, that each of its three colonial families is monophyletic, and that there have been at least three independent origins of cellular differentiation in the group, other studies call into question one or more of these conclusions. An accurate assessment of the evolutionary history of the volvocine algae requires inference of a more robust phylogeny.

RESULTS: We performed RNA sequencing (RNA-seq) on 55 strains representing 47 volvocine algal species and obtained similar data from curated databases on 13 additional strains. We then compiled a dataset consisting of transcripts for 40 single-copy, protein-coding, nuclear genes and subjected the predicted amino acid sequences of these genes to maximum likelihood, Bayesian inference, and coalescent-based analyses. These analyses show that multicellularity independently evolved at least twice in the volvocine algae and that the colonial family Goniaceae is not monophyletic. Our data further indicate that cellular differentiation arose independently at least four, and possibly as many as six times, within the volvocine algae.

CONCLUSIONS: Altogether, our results demonstrate that multicellularity and cellular differentiation are evolutionarily labile in the volvocine algae, affirming the importance of this group as a model system for the study of major transitions in the history of life.}, } @article {pmid34463760, year = {2021}, author = {Diegmiller, R and Doherty, CA and Stern, T and Imran Alsous, J and Shvartsman, SY}, title = {Size scaling in collective cell growth.}, journal = {Development (Cambridge, England)}, volume = {148}, number = {18}, pages = {}, pmid = {34463760}, issn = {1477-9129}, support = {R01 GM134204/GM/NIGMS NIH HHS/United States ; F31 HD098835/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; Cell Proliferation/*physiology ; Developmental Biology/methods ; Diptera/physiology ; Germ Cells/physiology ; Oogenesis/physiology ; Organelles/physiology ; }, abstract = {Size is a fundamental feature of living entities and is intimately tied to their function. Scaling laws, which can be traced to D'Arcy Thompson and Julian Huxley, have emerged as a powerful tool for studying regulation of the growth dynamics of organisms and their constituent parts. Yet, throughout the 20th century, as scaling laws were established for single cells, quantitative studies of the coordinated growth of multicellular structures have lagged, largely owing to technical challenges associated with imaging and image processing. Here, we present a supervised learning approach for quantifying the growth dynamics of germline cysts during oogenesis. Our analysis uncovers growth patterns induced by the groupwise developmental dynamics among connected cells, and differential growth rates of their organelles. We also identify inter-organelle volumetric scaling laws, finding that nurse cell growth is linear over several orders of magnitude. Our approach leverages the ever-increasing quantity and quality of imaging data, and is readily amenable for studies of collective cell growth in other developmental contexts, including early mammalian embryogenesis and germline development.}, } @article {pmid34462837, year = {2021}, author = {Mikhalevich, VI}, title = {Aromorphoses in the Evolution of Unicellular Eukaryotes (as Exemplified by Foraminifera D'orbigny, 1826).}, journal = {Doklady biological sciences : proceedings of the Academy of Sciences of the USSR, Biological sciences sections}, volume = {499}, number = {1}, pages = {105-108}, pmid = {34462837}, issn = {1608-3105}, mesh = {Eukaryota ; *Foraminifera/genetics ; }, abstract = {Aromorphoses of unicellular organisms are almost unexplored. Foraminifera provide a unique opportunity of such studies, having the most complex structure and being most fully represented in the geological record. In their development, more than 10 aromorphoses (key advances) have first been discovered, which arose in different classes of Foraminifera independently and in parallel. Of these, the key ones are the emergence of an agglutinated and then secreted calcareous shell, a bifontinal (bilamellar) wall, multichamberedness, differentiation of chambers, an integrating system of channels and nuclear dualism. They represent peculiar ways of evolution at the unicellular level. Multicameredness can be compared with multicellularity; differentiation of chambers, with differentiation of tissues; a system of channels, striking in its complexity and carrying O2, with the Metazoa circulatory system.}, } @article {pmid34455760, year = {2021}, author = {Louka, A and Takan, I and Pavlopoulou, A and Georgakilas, AG}, title = {Bioinformatic approaches to the investigation of the atavistic genes implicated in cancer.}, journal = {Frontiers in bioscience (Landmark edition)}, volume = {26}, number = {8}, pages = {279-311}, doi = {10.52586/4944}, pmid = {34455760}, issn = {2768-6698}, mesh = {Biological Evolution ; *Computational Biology ; Gene Regulatory Networks ; Humans ; *Neoplasms/genetics ; Phylogeny ; }, abstract = {Introduction: Cancer is a widespread phenomenon occurring across multicellular organisms and represents a condition of atavism, wherein cells follow a path of reverse evolution that unlocks a toolkit of ancient pre-existing adaptations by disturbing hub genes of the human gene network. This results to a primitive cellular phenotype which resembles a unicellular life form. Methods: In the present study, we have employed bioinformatic approaches for the in-depth investigation of twelve atavistic hub genes (ACTG1, CTNNA1, CTNND1, CTTN, DSP, ILK, PKN2, PKP3, PLEC, RCC2, TLN1 and VASP), which exhibit highly disrupted interactions in diverse types of cancer and are associated with the formation of metastasis. To this end, phylogenetic analyses were conducted towards unravelling the evolutionary history of those hubs and tracing the origin of cancer in the Tree of Life. Results: Based on our results, most of those genes are of unicellular origin, and some of them can be traced back to the emergence of cellular life itself (atavistic theory). Our findings indicate how deep the evolutionary roots of cancer actually are, and may be exploited in the clinical setting for the design of novel therapeutic approaches and, particularly, in overcoming resistance to antineoplastic treatment.}, } @article {pmid34440622, year = {2021}, author = {Mandujano-Tinoco, EA and Sultan, E and Ottolenghi, A and Gershoni-Yahalom, O and Rosental, B}, title = {Evolution of Cellular Immunity Effector Cells; Perspective on Cytotoxic and Phagocytic Cellular Lineages.}, journal = {Cells}, volume = {10}, number = {8}, pages = {}, pmid = {34440622}, issn = {2073-4409}, mesh = {Animals ; Bacteria/immunology/pathogenicity ; *Cell Lineage ; Communicable Diseases/*immunology/metabolism ; *Cytotoxicity, Immunologic ; Host-Pathogen Interactions ; Humans ; *Immunity, Cellular ; *Immunity, Innate ; Parasites/immunology/pathogenicity ; Phagocytes/*immunology/metabolism ; *Phagocytosis ; Signal Transduction ; Viruses/immunology/pathogenicity ; }, abstract = {The immune system has evolved to protect organisms from infections caused by bacteria, viruses, and parasitic pathogens. In addition, it provides regenerative capacities, tissue maintenance, and self/non-self recognition of foreign tissues. Phagocytosis and cytotoxicity are two prominent cellular immune activities positioned at the base of immune effector function in mammals. Although these immune mechanisms have diversified into a wide heterogeneous repertoire of effector cells, it appears that they share some common cellular and molecular features in all animals, but also some interesting convergent mechanisms. In this review, we will explore the current knowledge about the evolution of phagocytic and cytotoxic immune lineages against pathogens, in the clearance of damaged cells, for regeneration, for histocompatibility recognition, and in killing virally infected cells. To this end, we give different immune examples of multicellular organism models, ranging from the roots of bilateral organisms to chordate invertebrates, comparing to vertebrates' lineages. In this review, we compare cellular lineage homologies at the cellular and molecular levels. We aim to highlight and discuss the diverse function plasticity within the evolved immune effector cells, and even suggest the costs and benefits that it may imply for organisms with the meaning of greater defense against pathogens but less ability to regenerate damaged tissues and organs.}, } @article {pmid34430989, year = {2021}, author = {Suthar, J and Al-Jufaili, S and Bray, RA and Frank, M and Theisen, S and Palm, HW}, title = {Redescription of Aspidogaster limacoides Diesing, 1834 (Aspidogastrea: Aspidogastridae) from freshwater fishes of northern Germany.}, journal = {Parasitology research}, volume = {120}, number = {10}, pages = {3405-3416}, pmid = {34430989}, issn = {1432-1955}, mesh = {Animals ; *Cyprinidae ; Fishes ; Fresh Water ; Germany ; Phylogeny ; *Trematoda ; }, abstract = {Aspidogaster limacoides Diesing, 1834 (Aspidogastridae) is redescribed based on light and scanning electron microscopy of specimens from the stomach and intestine of Abramis brama, Rutilus rutilus and Scardinius erythrophthalmus (Actinopterygii: Cyprinidae). The fishes were sampled during 2018 and 2019 at Lake Tollense in Mecklenburg-Western Pomerania, Germany. The prevalence of A. limacoides was highest in R. rutilus (61.7%) followed by Scardinius erythrophthalmus (7.7%) and A. brama (2.9%), while it was absent in Perca fluviatilis from the same lake. The following structures of A. limacoides are described for the first time: a depression on the ventral side of the neck, variations in the number and the arrangement of alveoli, numerous pits scattered all over the body surface, the presence of a few papillae-like structures posterior lateral to the mouth, the number of marginal organs represented by openings of exocrine multicellular glands as shown in histology and the subterminal position of the excretory pore. These characters can be used to distinguish three species of Aspidogaster, namely, A. ijimai, A. conchicola and A. limacoides, suggesting that SEM is a useful and promising tool in differentiating Aspidogaster species. Comparison of molecular data of the ITS1-5.8S-ITS2 regions showed a 94% similarity to A. limacoides from the European part of Russia. Phylogenetic analysis showed that the present specimens clustered in the same clade with A. limacoides sensu stricto, forming a distinct group to the exclusion of congeners.}, } @article {pmid34411089, year = {2021}, author = {Leray, M and Wilkins, LGE and Apprill, A and Bik, HM and Clever, F and Connolly, SR and De León, ME and Duffy, JE and Ezzat, L and Gignoux-Wolfsohn, S and Herre, EA and Kaye, JZ and Kline, DI and Kueneman, JG and McCormick, MK and McMillan, WO and O'Dea, A and Pereira, TJ and Petersen, JM and Petticord, DF and Torchin, ME and Vega Thurber, R and Videvall, E and Wcislo, WT and Yuen, B and Eisen, JA}, title = {Natural experiments and long-term monitoring are critical to understand and predict marine host-microbe ecology and evolution.}, journal = {PLoS biology}, volume = {19}, number = {8}, pages = {e3001322}, pmid = {34411089}, issn = {1545-7885}, mesh = {*Acclimatization ; Animals ; Aquatic Organisms/*microbiology ; *Biological Evolution ; *Ecology ; Ecosystem ; Humans ; *Microbiota ; Symbiosis ; }, abstract = {Marine multicellular organisms host a diverse collection of bacteria, archaea, microbial eukaryotes, and viruses that form their microbiome. Such host-associated microbes can significantly influence the host's physiological capacities; however, the identity and functional role(s) of key members of the microbiome ("core microbiome") in most marine hosts coexisting in natural settings remain obscure. Also unclear is how dynamic interactions between hosts and the immense standing pool of microbial genetic variation will affect marine ecosystems' capacity to adjust to environmental changes. Here, we argue that significantly advancing our understanding of how host-associated microbes shape marine hosts' plastic and adaptive responses to environmental change requires (i) recognizing that individual host-microbe systems do not exist in an ecological or evolutionary vacuum and (ii) expanding the field toward long-term, multidisciplinary research on entire communities of hosts and microbes. Natural experiments, such as time-calibrated geological events associated with well-characterized environmental gradients, provide unique ecological and evolutionary contexts to address this challenge. We focus here particularly on mutualistic interactions between hosts and microbes, but note that many of the same lessons and approaches would apply to other types of interactions.}, } @article {pmid34404788, year = {2021}, author = {Galindo, LJ and López-García, P and Torruella, G and Karpov, S and Moreira, D}, title = {Phylogenomics of a new fungal phylum reveals multiple waves of reductive evolution across Holomycota.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {4973}, pmid = {34404788}, issn = {2041-1723}, mesh = {Basal Bodies ; Blastocladiomycota ; Chytridiomycota/classification ; Flagella ; Fungi/*classification/cytology/genetics/metabolism ; Genomics ; Hepatophyta/*classification ; Hyphae ; Phenotype ; *Phylogeny ; Specimen Handling ; Transcriptome ; }, abstract = {Compared to multicellular fungi and unicellular yeasts, unicellular fungi with free-living flagellated stages (zoospores) remain poorly known and their phylogenetic position is often unresolved. Recently, rRNA gene phylogenetic analyses of two atypical parasitic fungi with amoeboid zoospores and long kinetosomes, the sanchytrids Amoeboradix gromovi and Sanchytrium tribonematis, showed that they formed a monophyletic group without close affinity with known fungal clades. Here, we sequence single-cell genomes for both species to assess their phylogenetic position and evolution. Phylogenomic analyses using different protein datasets and a comprehensive taxon sampling result in an almost fully-resolved fungal tree, with Chytridiomycota as sister to all other fungi, and sanchytrids forming a well-supported, fast-evolving clade sister to Blastocladiomycota. Comparative genomic analyses across fungi and their allies (Holomycota) reveal an atypically reduced metabolic repertoire for sanchytrids. We infer three main independent flagellum losses from the distribution of over 60 flagellum-specific proteins across Holomycota. Based on sanchytrids' phylogenetic position and unique traits, we propose the designation of a novel phylum, Sanchytriomycota. In addition, our results indicate that most of the hyphal morphogenesis gene repertoire of multicellular fungi had already evolved in early holomycotan lineages.}, } @article {pmid34394122, year = {2021}, author = {Sun, V and Sharpley, M and Kaczor-Urbanowicz, KE and Chang, P and Montel-Hagen, A and Lopez, S and Zampieri, A and Zhu, Y and de Barros, SC and Parekh, C and Casero, D and Banerjee, U and Crooks, GM}, title = {The Metabolic Landscape of Thymic T Cell Development In Vivo and In Vitro.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {716661}, pmid = {34394122}, issn = {1664-3224}, support = {P30 AG028748/AG/NIA NIH HHS/United States ; P30 CA016042/CA/NCI NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; T32 GM008042/GM/NIGMS NIH HHS/United States ; UL1 TR000124/TR/NCATS NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; Biomarkers ; *Cell Differentiation ; Cell Line ; Computational Biology/methods ; *Energy Metabolism ; Gene Expression Profiling ; Hematopoietic Stem Cells/cytology/immunology/metabolism ; Humans ; Lymphopoiesis ; Metabolome ; Metabolomics/methods ; Mice ; Organoids ; T-Lymphocytes/*cytology/*metabolism ; Thymocytes/*cytology/immunology/*metabolism ; Tissue Culture Techniques ; }, abstract = {Although metabolic pathways have been shown to control differentiation and activation in peripheral T cells, metabolic studies on thymic T cell development are still lacking, especially in human tissue. In this study, we use transcriptomics and extracellular flux analyses to investigate the metabolic profiles of primary thymic and in vitro-derived mouse and human thymocytes. Core metabolic pathways, specifically glycolysis and oxidative phosphorylation, undergo dramatic changes between the double-negative (DN), double-positive (DP), and mature single-positive (SP) stages in murine and human thymus. Remarkably, despite the absence of the complex multicellular thymic microenvironment, in vitro murine and human T cell development recapitulated the coordinated decrease in glycolytic and oxidative phosphorylation activity between the DN and DP stages seen in primary thymus. Moreover, by inducing in vitro T cell differentiation from Rag1[-/-] mouse bone marrow, we show that reduced metabolic activity at the DP stage is independent of TCR rearrangement. Thus, our findings suggest that highly conserved metabolic transitions are critical for thymic T cell development.}, } @article {pmid34384851, year = {2021}, author = {Cisbani, G and Metherel, AH and Smith, ME and Bazinet, RP}, title = {Murine and human microglial cells are relatively enriched with eicosapentaenoic acid compared to the whole brain.}, journal = {Neurochemistry international}, volume = {150}, number = {}, pages = {105154}, doi = {10.1016/j.neuint.2021.105154}, pmid = {34384851}, issn = {1872-9754}, support = {//CIHR/Canada ; }, mesh = {Animals ; Brain/cytology/*metabolism ; Brain Chemistry/*physiology ; Eicosapentaenoic Acid/analysis/*metabolism ; Female ; Fetus ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Microglia/chemistry/*metabolism ; }, abstract = {The brain is a multicellular organ enriched with lipids. While the fatty acid composition of gross cerebral tissue is well characterized, the fatty acid composition of specific brain cells, particularly microglia cells, is less well characterized. Microglia cells are the innate immune cells of the brain, and a paucity of studies measuring their fatty acid composition using either immortalized or primary microglia cells report a higher ratio of eicosapentaenoic acid (EPA) to docosahexaenoic acid (DHA) than widely observed in whole brain tissue. Here we further characterize the fatty acid composition of murine microglia cells from young male and female mice as well as of human origin and compared it with a myelin-enriched fraction from the same mice. Our results show that saturated and monounsaturated fatty acids are the most abundant followed by polyunsaturated fatty acids (PUFA), with no statistical differences between sexes. Regarding PUFA, although DHA levels did not differ between human and murine cells, EPA was statistically higher in murine microglia. Notably, the DHA to EPA ratio was about 400 times lower in microglial cells compared to the myelin-enriched fraction. Thus, our results suggest that as compared to whole brain tissue EPA is relatively abundant in microglia cells, particularly in comparison to other n-3 PUFA such as DHA. Since the fatty acid composition of microglia can influence their functionality, a better understanding of EPA and DHA metabolism in microglia and the brain could identify new targets to modify microglial activity.}, } @article {pmid34374500, year = {2021}, author = {Dzik, J}, title = {Metabolic evolutionary roots of the macrophage immune response in amoeba-bacteria interactions: The conserved role of hypoxia-induced Factor and AMP kinase.}, journal = {Acta biochimica Polonica}, volume = {68}, number = {3}, pages = {457-476}, doi = {10.18388/abp.2020_5683}, pmid = {34374500}, issn = {1734-154X}, mesh = {Adenylate Kinase/*metabolism ; Amoeba/immunology/*metabolism ; Animals ; Bacteria/immunology/*metabolism ; Cytokines/metabolism ; Glycolysis ; Humans ; Hypoxia/metabolism ; Hypoxia-Inducible Factor 1/*metabolism ; Immunity/immunology ; Legionella/immunology/metabolism ; Macrophages/*immunology ; NF-kappa B/metabolism ; Phagocytosis ; Toll-Like Receptors/metabolism ; }, abstract = {The bacteria Legionella, being able to infect both macrophages and protozoans, reduce oxidative phosphorylation and induce glycolysis, which allows pathogens to grow and replicate in these cells. In amoeba-like inflammatory macrophages (M1), the phagocytizing cells of the primary immune defense, an increase in the rate of glycolysis is followed by a decrease of oxidative phosphorylation. The opposite takes place in anti-inflammatory macrophages (M2). They change from glycolysis to oxidative metabolism when AMP-dependent kinase (AMPK) is activated by a high ratio of AMP/ATP. Stimulation of macrophages with anti-inflammatory cytokines causes activation of AMPK. Infection of macrophages with the parasitic flagellate Leishmania infantum induces a switch from an initial glycolytic phase to oxidative phase with the essential role of AMPK in this change. Activated AMPK induces catabolic pathways effectively producing ATP as well as processes requiring the energy supply. AMPK regulates the migration of cells and enhances the phagocytic activity of macrophages. In macrophages, bacterial products activate TLRs and NF-κB signaling, causing an increase of transcription of hypoxia-induced factor HIF-1α (a subunit of HIF-1). This brings about induction of the enzyme and transporter expression essential for glycolysis and the pentose phosphate pathway to proceed and makes biosynthetic processes and ROS production in macrophages possible. Hypoxia augments macrophage phagocytosis in a HIF-1α-dependent manner. Multicellular parasites experience changes in the availability of oxygen in their life cycle. In the nematode Ascaris suum, HIF participates in the pre-adaptation to hypoxic conditions after infection of their hosts. Also, the freshwater and marine invertebrates meet changes of oxygen concentrations. In the anaerobic branch of the respiratory chain of these invertebrates, fumarate serves as the terminal electron acceptor that is reduced to succinate in complex II of the ETC. In mammalian cells, accumulation of succinate under hypoxic conditions suggests that the mammalian complex II may reduce fumarate to succinate, too. The data reviewed here show that the ability to shift the cell metabolism towards glycolysis observed in activated macrophages can be traced back in evolution to metabolic changes characterizing protozoans infected with bacteria. Anabolic needs of multiplying bacteria direct host metabolism to glycolysis that produces, aside from ATP, precursors of the amino acids used by the pathogen for its protein synthesis. M1-activated mammalian macrophages behave in the same way. Regulation of metabolism in M1 and M2 macrophages is further enhanced by HIF-1 and AMPK, respectively. These archaic functions of AMPK and HIF, important also to control phagocytosis and cell migration were extended to embryonic development in multicellular organisms.}, } @article {pmid34371024, year = {2021}, author = {Bussey, KJ and Davies, PCW}, title = {Reverting to single-cell biology: The predictions of the atavism theory of cancer.}, journal = {Progress in biophysics and molecular biology}, volume = {165}, number = {}, pages = {49-55}, pmid = {34371024}, issn = {1873-1732}, support = {U54 CA217376/CA/NCI NIH HHS/United States ; }, mesh = {Bacteria/genetics ; Biological Evolution ; Gene Regulatory Networks ; Humans ; *Neoplasms/genetics ; Phenotype ; }, abstract = {Cancer or cancer-like phenomena pervade multicellular life, implying deep evolutionary roots. Many of the hallmarks of cancer recapitulate unicellular modalities, suggesting that cancer initiation and progression represent a systematic reversion to simpler ancestral phenotypes in response to a stress or insult. This so-called atavism theory may be tested using phylostratigraphy, which can be used to assign ages to genes. Several research groups have confirmed that cancer cells tend to over-express evolutionary older genes, and rewire the architecture linking unicellular and multicellular gene networks. In addition, some of the elevated mutation rate - a well-known hallmark of cancer - is actually self-inflicted, driven by genes found to be homologs of the ancient SOS genes activated in stressed bacteria, and employed to evolve biological workarounds. These findings have obvious implications for therapy.}, } @article {pmid34359962, year = {2021}, author = {Van Goor, J and Shakes, DC and Haag, ES}, title = {Fisher vs. the Worms: Extraordinary Sex Ratios in Nematodes and the Mechanisms that Produce Them.}, journal = {Cells}, volume = {10}, number = {7}, pages = {}, pmid = {34359962}, issn = {2073-4409}, mesh = {Animals ; Fertility/*physiology ; Humans ; Male ; Nematoda/*metabolism ; Reproduction/*physiology ; Selection, Genetic ; *Sex Ratio ; Spermatozoa/cytology ; }, abstract = {Parker, Baker, and Smith provided the first robust theory explaining why anisogamy evolves in parallel in multicellular organisms. Anisogamy sets the stage for the emergence of separate sexes, and for another phenomenon with which Parker is associated: sperm competition. In outcrossing taxa with separate sexes, Fisher proposed that the sex ratio will tend towards unity in large, randomly mating populations due to a fitness advantage that accrues in individuals of the rarer sex. This creates a vast excess of sperm over that required to fertilize all available eggs, and intense competition as a result. However, small, inbred populations can experience selection for skewed sex ratios. This is widely appreciated in haplodiploid organisms, in which females can control the sex ratio behaviorally. In this review, we discuss recent research in nematodes that has characterized the mechanisms underlying highly skewed sex ratios in fully diploid systems. These include self-fertile hermaphroditism and the adaptive elimination of sperm competition factors, facultative parthenogenesis, non-Mendelian meiotic oddities involving the sex chromosomes, and environmental sex determination. By connecting sex ratio evolution and sperm biology in surprising ways, these phenomena link two "seminal" contributions of G. A. Parker.}, } @article {pmid34356075, year = {2021}, author = {Kloareg, B and Badis, Y and Cock, JM and Michel, G}, title = {Role and Evolution of the Extracellular Matrix in the Acquisition of Complex Multicellularity in Eukaryotes: A Macroalgal Perspective.}, journal = {Genes}, volume = {12}, number = {7}, pages = {}, pmid = {34356075}, issn = {2073-4425}, mesh = {Animals ; *Biological Evolution ; Eukaryota/classification/*physiology ; Extracellular Matrix/*physiology ; Seaweed/classification/*physiology ; }, abstract = {Multicellular eukaryotes are characterized by an expanded extracellular matrix (ECM) with a diversified composition. The ECM is involved in determining tissue texture, screening cells from the outside medium, development, and innate immunity, all of which are essential features in the biology of multicellular eukaryotes. This review addresses the origin and evolution of the ECM, with a focus on multicellular marine algae. We show that in these lineages the expansion of extracellular matrix played a major role in the acquisition of complex multicellularity through its capacity to connect, position, shield, and defend the cells. Multiple innovations were necessary during these evolutionary processes, leading to striking convergences in the structures and functions of the ECMs of algae, animals, and plants.}, } @article {pmid34356071, year = {2021}, author = {Petroll, R and Schreiber, M and Finke, H and Cock, JM and Gould, SB and Rensing, SA}, title = {Signatures of Transcription Factor Evolution and the Secondary Gain of Red Algae Complexity.}, journal = {Genes}, volume = {12}, number = {7}, pages = {}, pmid = {34356071}, issn = {2073-4425}, mesh = {*Evolution, Molecular ; *Genetic Variation ; *Genome ; *Phylogeny ; Rhodophyta/chemistry/*classification/*genetics/metabolism ; Transcription Factors/genetics/*metabolism ; }, abstract = {Red algae (Rhodophyta) belong to the superphylum Archaeplastida, and are a species-rich group exhibiting diverse morphologies. Theory has it that the unicellular red algal ancestor went through a phase of genome contraction caused by adaptation to extreme environments. More recently, the classes Porphyridiophyceae, Bangiophyceae, and Florideophyceae experienced genome expansions, coinciding with an increase in morphological complexity. Transcription-associated proteins (TAPs) regulate transcription, show lineage-specific patterns, and are related to organismal complexity. To better understand red algal TAP complexity and evolution, we investigated the TAP family complement of uni- and multi-cellular red algae. We found that the TAP family complement correlates with gain of morphological complexity in the multicellular Bangiophyceae and Florideophyceae, and that abundance of the C2H2 zinc finger transcription factor family may be associated with the acquisition of morphological complexity. An expansion of heat shock transcription factors (HSF) occurred within the unicellular Cyanidiales, potentially as an adaption to extreme environmental conditions.}, } @article {pmid34343611, year = {2021}, author = {Moroz, LL and Nikitin, MA and Poličar, PG and Kohn, AB and Romanova, DY}, title = {Evolution of glutamatergic signaling and synapses.}, journal = {Neuropharmacology}, volume = {199}, number = {}, pages = {108740}, pmid = {34343611}, issn = {1873-7064}, support = {R01 NS114491/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; Glutamic Acid/*physiology ; Receptors, Glutamate/*physiology ; Signal Transduction/*physiology ; Synapses/*physiology ; }, abstract = {Glutamate (Glu) is the primary excitatory transmitter in the mammalian brain. But, we know little about the evolutionary history of this adaptation, including the selection of l-glutamate as a signaling molecule in the first place. Here, we used comparative metabolomics and genomic data to reconstruct the genealogy of glutamatergic signaling. The origin of Glu-mediated communications might be traced to primordial nitrogen and carbon metabolic pathways. The versatile chemistry of L-Glu placed this molecule at the crossroad of cellular biochemistry as one of the most abundant metabolites. From there, innovations multiplied. Many stress factors or injuries could increase extracellular glutamate concentration, which led to the development of modular molecular systems for its rapid sensing in bacteria and archaea. More than 20 evolutionarily distinct families of ionotropic glutamate receptors (iGluRs) have been identified in eukaryotes. The domain compositions of iGluRs correlate with the origins of multicellularity in eukaryotes. Although L-Glu was recruited as a neuro-muscular transmitter in the early-branching metazoans, it was predominantly a non-neuronal messenger, with a possibility that glutamatergic synapses evolved more than once. Furthermore, the molecular secretory complexity of glutamatergic synapses in invertebrates (e.g., Aplysia) can exceed their vertebrate counterparts. Comparative genomics also revealed 15+ subfamilies of iGluRs across Metazoa. However, most of this ancestral diversity had been lost in the vertebrate lineage, preserving AMPA, Kainate, Delta, and NMDA receptors. The widespread expansion of glutamate synapses in the cortical areas might be associated with the enhanced metabolic demands of the complex brain and compartmentalization of Glu signaling within modular neuronal ensembles.}, } @article {pmid34343465, year = {2021}, author = {Anda, S and Boye, E and Schink, KO and Grallert, B}, title = {Cosegregation of asymmetric features during cell division.}, journal = {Open biology}, volume = {11}, number = {8}, pages = {210116}, pmid = {34343465}, issn = {2046-2441}, mesh = {*Cell Division ; Centrosome/*physiology ; *Chromosome Segregation ; Chromosomes, Fungal/*genetics ; *Mitosis ; Schizosaccharomyces/*physiology ; Spindle Apparatus/*physiology ; }, abstract = {Cellular asymmetry plays a major role in the ageing and evolution of multicellular organisms. However, it remains unknown how the cell distinguishes 'old' from 'new' and whether asymmetry is an attribute of highly specialized cells or a feature inherent in all cells. Here, we investigate the segregation of three asymmetric features: old and new DNA, the spindle pole body (SPB, the centrosome analogue) and the old and new cell ends, using a simple unicellular eukaryote, Schizosaccharomyces pombe. To our knowledge, this is the first study exploring three asymmetric features in the same cells. We show that of the three chromosomes of S. pombe, chromosome I containing the new parental strand, preferentially segregated to the cells inheriting the old cell end. Furthermore, the new SPB also preferentially segregated to the cells inheriting the old end. Our results suggest that the ability to distinguish 'old' from 'new' and to segregate DNA asymmetrically are inherent features even in simple unicellular eukaryotes.}, } @article {pmid34338785, year = {2022}, author = {Ramalho, JJ and Jones, VAS and Mutte, S and Weijers, D}, title = {Pole position: How plant cells polarize along the axes.}, journal = {The Plant cell}, volume = {34}, number = {1}, pages = {174-192}, pmid = {34338785}, issn = {1532-298X}, mesh = {Biological Evolution ; *Cell Polarity ; *Phylogeny ; Plant Cells/*physiology ; *Plant Physiological Phenomena ; Plant Proteins/*classification ; }, abstract = {Having a sense of direction is a fundamental cellular trait that can determine cell shape, division orientation, or function, and ultimately the formation of a functional, multicellular body. Cells acquire and integrate directional information by establishing discrete subcellular domains along an axis with distinct molecular profiles, a process known as cell polarization. Insight into the principles and mechanisms underlying cell polarity has been propelled by decades of extensive research mostly in yeast and animal models. Our understanding of cell polarity establishment in plants, which lack most of the regulatory molecules identified in other eukaryotes, is more limited, but significant progress has been made in recent years. In this review, we explore how plant cells coordinately establish stable polarity axes aligned with the organ axes, highlighting similarities in the molecular logic used to polarize both plant and animal cells. We propose a classification system for plant cell polarity events and nomenclature guidelines. Finally, we provide a deep phylogenetic analysis of polar proteins and discuss the evolution of polarity machineries in plants.}, } @article {pmid34302147, year = {2021}, author = {Zhao, YG and Codogno, P and Zhang, H}, title = {Machinery, regulation and pathophysiological implications of autophagosome maturation.}, journal = {Nature reviews. Molecular cell biology}, volume = {22}, number = {11}, pages = {733-750}, pmid = {34302147}, issn = {1471-0080}, mesh = {Autophagosomes/*genetics ; Autophagy/*genetics ; Endosomes/genetics ; Humans ; Lysosomes/genetics ; Neurodegenerative Diseases/*genetics/pathology ; Phagosomes/genetics ; Protein Processing, Post-Translational/genetics ; SNARE Proteins/genetics ; Transport Vesicles/*genetics ; rab GTP-Binding Proteins/genetics ; }, abstract = {Autophagy is a versatile degradation system for maintaining cellular homeostasis whereby cytosolic materials are sequestered in a double-membrane autophagosome and subsequently delivered to lysosomes, where they are broken down. In multicellular organisms, newly formed autophagosomes undergo a process called 'maturation', in which they fuse with vesicles originating from endolysosomal compartments, including early/late endosomes and lysosomes, to form amphisomes, which eventually become degradative autolysosomes. This fusion process requires the concerted actions of multiple regulators of membrane dynamics, including SNAREs, tethering proteins and RAB GTPases, and also transport of autophagosomes and late endosomes/lysosomes towards each other. Multiple mechanisms modulate autophagosome maturation, including post-translational modification of key components, spatial distribution of phosphoinositide lipid species on membranes, RAB protein dynamics, and biogenesis and function of lysosomes. Nutrient status and various stresses integrate into the autophagosome maturation machinery to coordinate the progression of autophagic flux. Impaired autophagosome maturation is linked to the pathogenesis of various human diseases, including neurodegenerative disorders, cancer and myopathies. Furthermore, invading pathogens exploit various strategies to block autophagosome maturation, thus evading destruction and even subverting autophagic vacuoles (autophagosomes, amphisomes and autolysosomes) for survival, growth and/or release. Here, we discuss the recent progress in our understanding of the machinery and regulation of autophagosome maturation, the relevance of these mechanisms to human pathophysiology and how they are harnessed by pathogens for their benefit. We also provide perspectives on targeting autophagosome maturation therapeutically.}, } @article {pmid34293333, year = {2021}, author = {Kożyczkowska, A and Najle, SR and Ocaña-Pallarès, E and Aresté, C and Shabardina, V and Ara, PS and Ruiz-Trillo, I and Casacuberta, E}, title = {Stable transfection in protist Corallochytrium limacisporum identifies novel cellular features among unicellular animals relatives.}, journal = {Current biology : CB}, volume = {31}, number = {18}, pages = {4104-4110.e5}, doi = {10.1016/j.cub.2021.06.061}, pmid = {34293333}, issn = {1879-0445}, mesh = {Animals ; Cell Nucleus Division ; *Eukaryota/genetics ; *Fungi/genetics ; Phylogeny ; Transfection ; }, abstract = {The evolutionary path from protists to multicellular animals remains a mystery. Recent work on the genomes of several unicellular relatives of animals has shaped our understanding of the genetic changes that may have occurred in this transition.[1-3] However, the specific cellular modifications that took place to accommodate these changes remain unclear. To address this, we need to compare metazoan cells with those of their extant relatives, which are choanoflagellates, filastereans, ichthyosporeans, and corallochytreans/pluriformeans. Interestingly, these lineages display a range of developmental patterns potentially homologous to animal ones. Genetic tools have already been established in three of those lineages.[4-7] However, there are no genetic tools available for Corallochytrea. We here report the development of stable transfection in the corallochytrean Corallochytrium limacisporum. Using these tools, we discern previously unknown biological features of C. limacisporum. In particular, we identify two different paths for cell division-binary fission and coenocytic growth-that reveal a non-linear life cycle. Additionally, we found that C. limacisporum is binucleate for most of its life cycle, and that, contrary to what happens in most eukaryotes, nuclear division is decoupled from cellular division. Moreover, its actin cytoskeleton shares characteristics with both fungal and animal cells. The establishment of these tools in C. limacisporum fills an important gap in the unicellular relatives of animals, opening up new avenues of research to elucidate the specific cellular changes that occurred in the evolution of animals.}, } @article {pmid34279742, year = {2021}, author = {de Souza, ID and Reis, CF and Morais, DAA and Fernandes, VGS and Cavalcante, JVF and Dalmolin, RJS}, title = {Ancestry analysis indicates two different sets of essential genes in eukaryotic model species.}, journal = {Functional & integrative genomics}, volume = {21}, number = {3-4}, pages = {523-531}, pmid = {34279742}, issn = {1438-7948}, mesh = {Animals ; *Caenorhabditis elegans/genetics ; *Drosophila melanogaster/genetics ; *Evolution, Molecular ; *Genes, Essential ; Mice ; *Saccharomyces cerevisiae/genetics ; *Schizosaccharomyces/genetics ; }, abstract = {Essential genes are so-called because they are crucial for organism perpetuation. Those genes are usually related to essential functions to cellular metabolism or multicellular homeostasis. Deleterious alterations on essential genes produce a spectrum of phenotypes in multicellular organisms. The effects range from the impairment of the fertilization process, disruption of fetal development, to loss of reproductive capacity. Essential genes are described as more evolutionarily conserved than non-essential genes. However, there is no consensus about the relationship between gene essentiality and gene age. Here, we identified essential genes in five model eukaryotic species (Saccharomyces cerevisiae, Schizosaccharomyces pombe, Drosophila melanogaster, Caenorhabditis elegans, and Mus musculus) and estimate their evolutionary ancestry and their network properties. We observed that essential genes, on average, are older than other genes in all species investigated. The relationship of network properties and gene essentiality convey with previous findings, showing essential genes as important nodes in biological networks. As expected, we also observed that essential orthologs shared by the five species evaluated here are old. However, all the species evaluated here have a specific set of young essential genes not shared among them. Additionally, these two groups of essential genes are involved with distinct biological functions, suggesting two sets of essential genes: (i) a set of old essential genes common to all the evaluated species, regulating basic cellular functions, and (ii) a set of young essential genes exclusive to each species, which perform specific essential functions in each species.}, } @article {pmid34275698, year = {2022}, author = {Verdonck, R and Legrand, D and Jacob, S and Philippe, H}, title = {Phenotypic plasticity through disposable genetic adaptation in ciliates.}, journal = {Trends in microbiology}, volume = {30}, number = {2}, pages = {120-130}, doi = {10.1016/j.tim.2021.06.007}, pmid = {34275698}, issn = {1878-4380}, mesh = {Adaptation, Physiological/genetics ; Biological Evolution ; *Ciliophora/genetics ; *Paramecium/genetics ; }, abstract = {Ciliates have an extraordinary genetic system in which each cell harbors two distinct kinds of nucleus, a transcriptionally active somatic nucleus and a quiescent germline nucleus. The latter undergoes classical, heritable genetic adaptation, while adaptation of the somatic nucleus is only short-term and thus disposable. The ecological and evolutionary relevance of this nuclear dimorphism have never been well formalized, which is surprising given the long history of using ciliates such as Tetrahymena and Paramecium as model organisms. We present a novel, alternative explanation for ciliate nuclear dimorphism which, we argue, should be considered an instrument of phenotypic plasticity by somatic selection on the level of the ciliate clone, as if it were a diffuse multicellular organism. This viewpoint helps to put some enigmatic aspects of ciliate biology into perspective and presents the diversity of ciliates as a large natural experiment that we can exploit to study phenotypic plasticity and organismality.}, } @article {pmid34268901, year = {2021}, author = {Bik, HM}, title = {Just keep it simple? Benchmarking the accuracy of taxonomy assignment software in metabarcoding studies.}, journal = {Molecular ecology resources}, volume = {21}, number = {7}, pages = {2187-2189}, doi = {10.1111/1755-0998.13473}, pmid = {34268901}, issn = {1755-0998}, mesh = {Animals ; *Benchmarking ; Biodiversity ; *DNA Barcoding, Taxonomic ; Humans ; Phylogeny ; RNA, Ribosomal, 16S ; Software ; }, abstract = {How do you put a name on an unknown piece of DNA? From microbes to mammals, high-throughput metabarcoding studies provide a more objective view of natural communities, overcoming many of the inherent limitations of traditional field surveys and microscopy-based observations (Deiner et al., 2017). Taxonomy assignment is one of the most critical aspects of any metabarcoding study, yet this important bioinformatics task is routinely overlooked. Biodiversity surveys and conservation efforts often depend on formal species inventories: the presence (or absence) of species, and the number of individuals reported across space and time. However, computational workflows applied in eukaryotic metabarcoding studies were originally developed for use with bacterial/archaeal data sets, where microbial researchers rely on one conserved locus (nuclear 16S rRNA) and have access to vast databases with good coverage across most prokaryotic lineages - a situation not mirrored in most multicellular taxa. In this issue of Molecular Ecology Resources, Hleap et al. (2021) carry out an extensive benchmarking exercise focused on taxonomy assignment strategies for eukaryotic metabarcoding studies utilizing the mitochondrial Cytochrome C oxidase I marker gene (COI). They assess the performance and accuracy of software tools representing diverse methodological approaches: from "simple" strategies based on sequence similarity and composition, to model-based phylogenetic and probabilistic classification tools. Contrary to popular assumptions, less complex approaches (BLAST and the QIIME2 feature classifier) consistently outperformed more sophisticated mathematical algorithms and were highly accurate for assigning taxonomy at higher levels (e.g. family). Lower-level assignments at the genus and species level still pose significant challenge for most existing algorithms, and sparse eukaryotic reference databases further limit software performance. This study illuminates current best practices for metabarcoding taxonomy assignments, and underscores the need for community-driven efforts to expand taxonomic and geographic representation in reference DNA barcode databases.}, } @article {pmid34264933, year = {2021}, author = {Loidl, J}, title = {Tetrahymena meiosis: Simple yet ingenious.}, journal = {PLoS genetics}, volume = {17}, number = {7}, pages = {e1009627}, pmid = {34264933}, issn = {1553-7404}, support = {P 31606/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Chromosome Painting ; *Epigenesis, Genetic ; *Meiosis ; Reproduction/*physiology ; Tetrahymena thermophila/*genetics ; }, abstract = {The presence of meiosis, which is a conserved component of sexual reproduction, across organisms from all eukaryotic kingdoms, strongly argues that sex is a primordial feature of eukaryotes. However, extant meiotic structures and processes can vary considerably between organisms. The ciliated protist Tetrahymena thermophila, which diverged from animals, plants, and fungi early in evolution, provides one example of a rather unconventional meiosis. Tetrahymena has a simpler meiosis compared with most other organisms: It lacks both a synaptonemal complex (SC) and specialized meiotic machinery for chromosome cohesion and has a reduced capacity to regulate meiotic recombination. Despite this, it also features several unique mechanisms, including elongation of the nucleus to twice the cell length to promote homologous pairing and prevent recombination between sister chromatids. Comparison of the meiotic programs of Tetrahymena and higher multicellular organisms may reveal how extant meiosis evolved from proto-meiosis.}, } @article {pmid34257365, year = {2021}, author = {Bestová, H and Segrestin, J and von Schwartzenberg, K and Škaloud, P and Lenormand, T and Violle, C}, title = {Biological scaling in green algae: the role of cell size and geometry.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {14425}, pmid = {34257365}, issn = {2045-2322}, mesh = {*Cell Size ; *Chlorophyta ; Models, Biological ; }, abstract = {The Metabolic Scaling Theory (MST), hypothesizes limitations of resource-transport networks in organisms and predicts their optimization into fractal-like structures. As a result, the relationship between population growth rate and body size should follow a cross-species universal quarter-power scaling. However, the universality of metabolic scaling has been challenged, particularly across transitions from bacteria to protists to multicellulars. The population growth rate of unicellulars should be constrained by external diffusion, ruling nutrient uptake, and internal diffusion, operating nutrient distribution. Both constraints intensify with increasing size possibly leading to shifting in the scaling exponent. We focused on unicellular algae Micrasterias. Large size and fractal-like morphology make this species a transitional group between unicellular and multicellular organisms in the evolution of allometry. We tested MST predictions using measurements of growth rate, size, and morphology-related traits. We showed that growth scaling of Micrasterias follows MST predictions, reflecting constraints by internal diffusion transport. Cell fractality and density decrease led to a proportional increase in surface area with body mass relaxing external constraints. Complex allometric optimization enables to maintain quarter-power scaling of population growth rate even with a large unicellular plan. Overall, our findings support fractality as a key factor in the evolution of biological scaling.}, } @article {pmid34244514, year = {2021}, author = {Bernardes, JP and John, U and Woltermann, N and Valiadi, M and Hermann, RJ and Becks, L}, title = {The evolution of convex trade-offs enables the transition towards multicellularity.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {4222}, pmid = {34244514}, issn = {2041-1723}, mesh = {Animals ; *Biological Evolution ; Cell Survival/physiology ; Chlamydomonas reinhardtii/*physiology ; *Models, Biological ; Predatory Behavior ; Rotifera/physiology ; }, abstract = {The evolutionary transition towards multicellular life often involves growth in groups of undifferentiated cells followed by differentiation into soma and germ-like cells. Theory predicts that germ soma differentiation is facilitated by a convex trade-off between survival and reproduction. However, this has never been tested and these transitions remain poorly understood at the ecological and genetic level. Here, we study the evolution of cell groups in ten isogenic lines of the unicellular green algae Chlamydomonas reinhardtii with prolonged exposure to a rotifer predator. We confirm that growth in cell groups is heritable and characterized by a convex trade-off curve between reproduction and survival. Identical mutations evolve in all cell group isolates; these are linked to survival and reducing associated cell costs. Overall, we show that just 500 generations of predator selection were sufficient to lead to a convex trade-off and incorporate evolved changes into the prey genome.}, } @article {pmid34236522, year = {2021}, author = {Vigneau, J and Borg, M}, title = {The epigenetic origin of life history transitions in plants and algae.}, journal = {Plant reproduction}, volume = {34}, number = {4}, pages = {267-285}, pmid = {34236522}, issn = {2194-7961}, mesh = {Animals ; Biological Evolution ; *Chlorophyta ; Epigenesis, Genetic ; Germ Cells, Plant ; *Magnoliopsida/genetics ; Phylogeny ; Plants/genetics ; }, abstract = {Plants and algae have a complex life history that transitions between distinct life forms called the sporophyte and the gametophyte. This phenomenon-called the alternation of generations-has fascinated botanists and phycologists for over 170 years. Despite the mesmerizing array of life histories described in plants and algae, we are only now beginning to learn about the molecular mechanisms controlling them and how they evolved. Epigenetic silencing plays an essential role in regulating gene expression during multicellular development in eukaryotes, raising questions about its impact on the life history strategy of plants and algae. Here, we trace the origin and function of epigenetic mechanisms across the plant kingdom, from unicellular green algae through to angiosperms, and attempt to reconstruct the evolutionary steps that influenced life history transitions during plant evolution. Central to this evolutionary scenario is the adaption of epigenetic silencing from a mechanism of genome defense to the repression and control of alternating generations. We extend our discussion beyond the green lineage and highlight the peculiar case of the brown algae. Unlike their unicellular diatom relatives, brown algae lack epigenetic silencing pathways common to animals and plants yet display complex life histories, hinting at the emergence of novel life history controls during stramenopile evolution.}, } @article {pmid34215938, year = {2021}, author = {Machado, SR and Rodrigues, TM}, title = {Apoplasmic barrier in the extrafloral nectary of Citharexylum myrianthum (Verbenaceae).}, journal = {Planta}, volume = {254}, number = {2}, pages = {19}, pmid = {34215938}, issn = {1432-2048}, mesh = {Biological Transport ; Cell Wall ; Plant Nectar ; Trichomes ; *Verbenaceae ; }, abstract = {The cytological changes underlying the formation of an apoplasmic barrier in the multi-layered extrafloral nectaries of Citharexylum myrianthum are compatible with the synthesis, transport and deposition of suberin. In terms of ontogenesis and function, the intermediate layers of these nectaries are homologous with the stalks of nectar-secreting trichomes. Anticlinal cell wall impregnations are common in trichomatic nectaries and their functions as endodermis-like barriers have been discussed because of possible direct effects on the nectary physiology, mainly in the nectar secretion and resorption. However, the cytological events linked to nectary wall impregnations remain little explored. This study documents the ontogenesis and the fine structure of the EFN cells, and cytological events linked to the wall impregnations of multi-layered extrafloral nectaries (EFNs) in Citharexylum myrianthum Cham. (Verbenaceae). EFNs are patelliform, and differentiated into (a) a multicellular foot, which is compound in structure and vascularised with phloem strands, (b) a bi-layered intermediate region with thickened cell walls and (c) a single-layered secretory region with palisade-like cells. EFNs are protodermal in origin, starting with a single protodermal cell and ending with the complex, multi-layered structure. The cell wall impregnations first appear in the very young EFN and increase towards maturity. Lipid patches (assumed to be suberin) are deposited on the inner faces of the primary walls, first along the anticlinal walls and then extend to the periclinal walls. On both walls, plasmodesmata remain apparently intact during the maturation of the EFNs. In the peripheral cytoplasm there are abundant polymorphic plastids, well-developed Golgi bodies often close to rough endoplasmic reticulum profiles, mitochondria and polyribosomes. Cytological events linked to the wall impregnations are consistent with suberin synthesis, transport and deposition. Our findings offer new insights into the structure-properties of specialised nectary cell walls and so should contribute to our knowledge of the physiological and protective roles of this structure in nectar glands.}, } @article {pmid34204452, year = {2021}, author = {Cricrì, G and Bellucci, L and Montini, G and Collino, F}, title = {Urinary Extracellular Vesicles: Uncovering the Basis of the Pathological Processes in Kidney-Related Diseases.}, journal = {International journal of molecular sciences}, volume = {22}, number = {12}, pages = {}, pmid = {34204452}, issn = {1422-0067}, mesh = {Animals ; Biomarkers/*urine ; Cell Communication ; Cell-Derived Microparticles/metabolism ; Chemical Fractionation ; Disease Management ; Disease Susceptibility ; Exosomes/metabolism ; Extracellular Vesicles/*metabolism ; Humans ; Kidney Diseases/diagnosis/etiology/*metabolism/urine ; Liquid Biopsy/methods ; Precision Medicine/methods ; Urinalysis/methods ; }, abstract = {Intercellular communication governs multicellular interactions in complex organisms. A variety of mechanisms exist through which cells can communicate, e.g., cell-cell contact, the release of paracrine/autocrine soluble molecules, or the transfer of extracellular vesicles (EVs). EVs are membrane-surrounded structures released by almost all cell types, acting both nearby and distant from their tissue/organ of origin. In the kidney, EVs are potent intercellular messengers released by all urinary system cells and are involved in cell crosstalk, contributing to physiology and pathogenesis. Moreover, urine is a reservoir of EVs coming from the circulation after crossing the glomerular filtration barrier-or originating in the kidney. Thus, urine represents an alternative source for biomarkers in kidney-related diseases, potentially replacing standard diagnostic techniques, including kidney biopsy. This review will present an overview of EV biogenesis and classification and the leading procedures for isolating EVs from body fluids. Furthermore, their role in intra-nephron communication and their use as a diagnostic tool for precision medicine in kidney-related disorders will be discussed.}, } @article {pmid34199921, year = {2021}, author = {Mikuła, A and Tomaszewicz, W and Dziurka, M and Kaźmierczak, A and Grzyb, M and Sobczak, M and Zdańkowski, P and Rybczyński, J}, title = {The Origin of the Cyathea delgadii Sternb. Somatic Embryos Is Determined by the Developmental State of Donor Tissue and Mutual Balance of Selected Metabolites.}, journal = {Cells}, volume = {10}, number = {6}, pages = {}, pmid = {34199921}, issn = {2073-4409}, mesh = {Cytokinins/*pharmacology ; Ferns/cytology/*metabolism ; *Plant Somatic Embryogenesis Techniques ; }, abstract = {Somatic embryogenesis is the formation of a plant embryo from a cell other than the product of gametic fusion. The need to recognize the determinants of somatic cell fate has prompted investigations on how endogenous factors of donor tissues can determine the pattern of somatic embryo origin. The undertaking of this study was enabled by the newly developed experimental system of somatic embryogenesis of the tree fern Cyathea delgadii Sternb., in which the embryos are produced in hormone-free medium. The contents of 89 endogenous compounds (such as sugars, auxins, cytokinins, gibberellins, stress-related hormones, phenolic acids, polyamines, and amino acids) and cytomorphological features were compared between two types of explants giving rise to somatic embryos of unicellular or multicellular origin. We found that a large content of maltose, 1-kestose, abscisic acid, biologically active gibberellins, and phenolic acids was characteristic for single-cell somatic embryo formation pattern. In contrast, high levels of starch, callose, kinetin riboside, arginine, and ethylene promoted their multicellular origin. Networks for visualization of the relations between studied compounds were constructed based on the data obtained from analyses of a Pearson correlation coefficient heatmap. Our findings present for the first time detailed features of donor tissue that can play an important role in the somatic-to-embryogenic transition and the somatic embryo origin.}, } @article {pmid34181730, year = {2021}, author = {Wu, X and Yan, A and McAdam, SAM and Banks, JA and Zhang, S and Zhou, Y}, title = {Timing of meristem initiation and maintenance determines the morphology of fern gametophytes.}, journal = {Journal of experimental botany}, volume = {72}, number = {20}, pages = {6990-7001}, doi = {10.1093/jxb/erab307}, pmid = {34181730}, issn = {1460-2431}, mesh = {Biological Evolution ; *Ferns ; Germ Cells, Plant ; Meristem ; *Pteridaceae ; }, abstract = {The alternation of generations in land plants occurs between the sporophyte phase and the gametophyte phase. The sporophytes of seed plants develop self-maintained, multicellular meristems, and these meristems determine plant architecture. The gametophytes of seed plants lack meristems and are heterotrophic. In contrast, the gametophytes of seed-free vascular plants, including ferns, are autotrophic and free-living, developing meristems to sustain their independent growth and proliferation. Compared with meristems in the sporophytes of seed plants, the cellular mechanisms underlying meristem development in fern gametophytes remain largely unknown. Here, using confocal time-lapse live imaging and computational segmentation and quantification, we determined different patterns of cell divisions associated with the initiation and proliferation of two distinct types of meristems in gametophytes of two closely related Pteridaceae ferns, Pteris vittata and Ceratopteris richardii. Our results reveal how the simple timing of a switch between two meristems has considerable consequences for the divergent gametophyte morphologies of the two ferns. They further provide evolutionary insight into the function and regulation of gametophyte meristems in seed-free vascular plants.}, } @article {pmid34161405, year = {2021}, author = {Tan, A and Liu, Q and Septiadi, D and Chu, S and Liu, T and Richards, SJ and Rothen-Rutishauser, B and Petri-Fink, A and Gibson, MI and Boyd, BJ}, title = {Understanding selectivity of metabolic labelling and click-targeting in multicellular environments as a route to tissue selective drug delivery.}, journal = {Journal of materials chemistry. B}, volume = {9}, number = {26}, pages = {5365-5373}, doi = {10.1039/d1tb00721a}, pmid = {34161405}, issn = {2050-7518}, support = {BB/M02878X/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Cell Line ; Click Chemistry ; Cyclooctanes/chemistry/*metabolism ; *Drug Delivery Systems ; Epithelial Cells/chemistry/metabolism ; Fibroblasts/chemistry/metabolism ; Gold/chemistry/*metabolism ; Hexosamines/chemistry/*metabolism ; Humans ; Metal Nanoparticles/*chemistry ; Molecular Structure ; Particle Size ; Polysaccharides/chemistry/*metabolism ; Surface Properties ; }, abstract = {Cancer cells generally exhibit higher metabolic demands relative to that of normal tissue cells. This offers great possibilities to exploit metabolic glycoengineering in combination with bio-orthogonal chemistry reactions to achieve tumour site-targeted therapeutic delivery. This work addresses the selectivity of metabolic glycan labelling in diseased (i.e., cancer) versus normal cells grown in a multicellular environment. Dibenzocylooctyne (DBCO)-bearing acetylated-d-mannosamine (Ac4ManNDBCO) was synthesised to metabolically label three different types of cell lines originating from the human lung tissues: A549 adenocarcinomic alveolar basal epithelial cells, MeT5A non-cancerous mesothelial cells, and MRC5 non-cancerous fibroblasts. These cell lines displayed different labelling sensitivity, which trended with their doubling time in the following order: A549 ≈ MeT5A > MRC5. The higher metabolic labelling efficiency inherently led to a higher extent of specific binding and accumulation of the clickable N3-conjugated gold nanoparticles (N3-AuNps, core diameter = 30 nm) in the DBCO-glycan modified A549 and MeT5A cells, but to a less prominent effect in MRC5 cells. These findings demonstrate that relative rates of cell metabolism can be exploited using metabolic labelling to recruit nanotherapeutics whilst minimising non-specific targeting of surrounding tissues.}, } @article {pmid34147614, year = {2021}, author = {Shang-Guan, XY and Cai, YJ and Xu, HZ and Cheng, X and Zhang, RF and Liu, HX}, title = {A C-type lectin with a single CRD from Onychostoma macrolepis mediates immune recognition against bacterial challenge.}, journal = {Fish & shellfish immunology}, volume = {115}, number = {}, pages = {160-170}, doi = {10.1016/j.fsi.2021.06.007}, pmid = {34147614}, issn = {1095-9947}, mesh = {Aeromonas hydrophila/physiology ; Amino Acid Sequence ; Animals ; Base Sequence ; Cyprinidae/*genetics/*immunology ; Fish Diseases/*immunology ; Fish Proteins/chemistry/genetics/immunology ; Gene Expression Profiling/veterinary ; Gene Expression Regulation/*immunology ; Gram-Negative Bacterial Infections/immunology/veterinary ; Immunity, Innate/*genetics ; Lectins, C-Type/chemistry/*genetics/*immunology ; Phylogeny ; Sequence Alignment/veterinary ; }, abstract = {C-type lectins (CTL) are a large group of pattern-recognition proteins and to play important roles in glycoprotein metabolism, multicellular integration, and immunity. Based on their overall domain structure, they can be classified as different groups that possess different physiological functions. A typical C-type lectin (named as OmLec1) was identified from the fish, Onychostoma macrolepis, an important cultured fish in China. Open reading frame of OmLec1 contains a 570 bp, encoding a protein of 189 amino acids that includes a signal peptide and a single carbohydrate-recognition domain. The phylogenetic analysis showed that OmLec1 could be grouped with C-type lectin from other fish. OmLec1 was expressed in all the tissues in our study, and the expression level was highest in liver. And its relative expression levels were significantly upregulated following infection with Aeromonas hydrophila. The recombinant OmLec1 protein (rOmLec1) could agglutinate some Gram-negative bacteria and Gram-positive bacteria in vitro in the presence of Ca[2+], showing a typical Ca[2+]-dependent carbohydrate-binding protein. Furthermore, rOmLec1 purified from E. coli BL21 (DE3), strongly bound to LPS and PGN, as well as all tested bacteria in a Ca[2+]-dependent manner. These results indicate that OmLec1 plays a central role in the innate immune response and as a pattern recognition receptor that recognizes diverse pathogens among O. macrolepis.}, } @article {pmid34147034, year = {2022}, author = {Caipa Garcia, AL and Arlt, VM and Phillips, DH}, title = {Organoids for toxicology and genetic toxicology: applications with drugs and prospects for environmental carcinogenesis.}, journal = {Mutagenesis}, volume = {37}, number = {2}, pages = {143-154}, pmid = {34147034}, issn = {1464-3804}, support = {MR/N013700/1/MRC_/Medical Research Council/United Kingdom ; /DH_/Department of Health/United Kingdom ; C98/A24032/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Animals ; Carcinogenesis ; Cell Culture Techniques ; Humans ; Mammals ; Models, Biological ; *Organoids ; *Pluripotent Stem Cells ; }, abstract = {Advances in three-dimensional (3D) cell culture technology have led to the development of more biologically and physiologically relevant models to study organ development, disease, toxicology and drug screening. Organoids have been derived from many mammalian tissues, both normal and tumour, from adult stem cells and from pluripotent stem cells. Tissue organoids can retain many of the cell types and much of the structure and function of the organ of origin. Organoids derived from pluripotent stem cells display increased complexity compared with organoids derived from adult stem cells. It has been shown that organoids express many functional xenobiotic-metabolising enzymes including cytochrome P450s (CYPs). This has benefitted the drug development field in facilitating pre-clinical testing of more personalised treatments and in developing large toxicity and efficacy screens for a range of compounds. In the field of environmental and genetic toxicology, treatment of organoids with various compounds has generated responses that are close to those obtained in primary tissues and in vivo models, demonstrating the biological relevance of these in vitro multicellular 3D systems. Toxicological investigations of compounds in different tissue organoids have produced promising results indicating that organoids will refine future studies on the effects of environmental exposures and carcinogenic risk to humans. With further development and standardised procedures, advancing our understanding on the metabolic capabilities of organoids will help to validate their use to investigate the modes of action of environmental carcinogens.}, } @article {pmid34133948, year = {2021}, author = {Puzakov, MV and Puzakova, LV and Cheresiz, SV and Sang, Y}, title = {The IS630/Tc1/mariner transposons in three ctenophore genomes.}, journal = {Molecular phylogenetics and evolution}, volume = {163}, number = {}, pages = {107231}, doi = {10.1016/j.ympev.2021.107231}, pmid = {34133948}, issn = {1095-9513}, mesh = {Animals ; *Ctenophora/genetics ; *Culicidae ; DNA Transposable Elements/genetics ; Phylogeny ; Transposases/genetics ; }, abstract = {Transposable elements (TEs) exert a significant effect on the structure and functioning of the genomes and also serve as a source of the new genes. The study of the TE diversity and evolution in different taxa is indispensable for the fundamental understanding of their roles in the genomes. IS630/Tc1/mariner (ITm) transposable elements represent the most prevalent and diverse group of DNA transposons. In this work, we studied the diversity, evolutionary dynamics and the phylogenetic relationships of the ITm transposons found in three ctenophore species: Mnemiopsis leidyi, Pleurobrachia bachei, Beroe ovata. We identified 29 ITm transposons, seven of which possess the terminal inverted repeats (TIRs) and an intact transposase, and, thus, are, presumably, active. Four other ITm transposons have the features of domesticated TEs. According to the results of the phylogenetic analysis, the ITm transposons of the ctenophores represent five groups - MLE/DD34D, TLE/DD34-38E, mosquito/DD37E, Visiror/DD41D and pogo/DDxD. Pogo/DDxD superfamily turnes out to be the most diverse and prevalent, since it accounts for more than 40% of the TEs identified. The data obtained in this research will fill the gap of knowledge of the diversity and evolution of the ITm transposons in the multicellular genomes and will lay the ground for the study of the TE effects on the evolution of the ctenophores.}, } @article {pmid34127736, year = {2021}, author = {Opazo, JC and Vandewege, MW and Gutierrez, J and Zavala, K and Vargas-Chacoff, L and Morera, FJ and Mardones, GA}, title = {Independent duplications of the Golgi phosphoprotein 3 oncogene in birds.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {12483}, pmid = {34127736}, issn = {2045-2322}, mesh = {Amino Acid Sequence/genetics ; Animals ; Birds/*genetics ; Carcinogenesis/genetics ; *Evolution, Molecular ; Gene Duplication ; Golgi Apparatus/*genetics ; Humans ; Membrane Proteins/*genetics ; Neoplasms/genetics ; Oncogene Proteins/*genetics ; Phosphoproteins/genetics ; Sequence Alignment ; }, abstract = {Golgi phosphoprotein 3 (GOLPH3) was the first reported oncoprotein of the Golgi apparatus. It was identified as an evolutionarily conserved protein upon its discovery about 20 years ago, but its function remains puzzling in normal and cancer cells. The GOLPH3 gene is part of a group of genes that also includes the GOLPH3L gene. Because cancer has deep roots in multicellular evolution, studying the evolution of the GOLPH3 gene family in non-model species represents an opportunity to identify new model systems that could help better understand the biology behind this group of genes. The main goal of this study is to explore the evolution of the GOLPH3 gene family in birds as a starting point to understand the evolutionary history of this oncoprotein. We identified a repertoire of three GOLPH3 genes in birds. We found duplicated copies of the GOLPH3 gene in all main groups of birds other than paleognaths, and a single copy of the GOLPH3L gene. We suggest there were at least three independent origins for GOLPH3 duplicates. Amino acid divergence estimates show that most of the variation is located in the N-terminal region of the protein. Our transcript abundance estimations show that one paralog is highly and ubiquitously expressed, and the others were variable. Our results are an example of the significance of understanding the evolution of the GOLPH3 gene family, especially for unraveling its structural and functional attributes.}, } @article {pmid34120565, year = {2021}, author = {Miguel-Tomé, S and Llinás, RR}, title = {Broadening the definition of a nervous system to better understand the evolution of plants and animals.}, journal = {Plant signaling & behavior}, volume = {16}, number = {10}, pages = {1927562}, pmid = {34120565}, issn = {1559-2324}, mesh = {Animals ; *Biological Evolution ; Electrophysiological Phenomena ; *Nervous System Physiological Phenomena ; *Plant Physiological Phenomena ; Signal Transduction ; Terminology as Topic ; }, abstract = {Most textbook definitions recognize only animals as having nervous systems. However, for the past couple decades, botanists have been meticulously studying long-distance signaling systems in plants, and some researchers have stated that plants have a simple nervous system. Thus, an academic conflict has emerged between those who defend and those who deny the existence of a nervous system in plants. This article analyses that debate, and we propose an alternative to answering yes or no: broadening the definition of a nervous system to include plants. We claim that a definition broader than the current one, which is based only on a phylogenetic viewpoint, would be helpful in obtaining a deeper understanding of how evolution has driven the features of signal generation, transmission and processing in multicellular beings. Also, we propose two possible definitions and exemplify how broader a definition allows for new viewpoints on the evolution of plants, animals and the nervous system.}, } @article {pmid34114051, year = {2021}, author = {Márquez-Zacarías, P and Conlin, PL and Tong, K and Pentz, JT and Ratcliff, WC}, title = {Why have aggregative multicellular organisms stayed simple?.}, journal = {Current genetics}, volume = {67}, number = {6}, pages = {871-876}, pmid = {34114051}, issn = {1432-0983}, mesh = {*Biological Evolution ; Clonal Evolution ; Eukaryota/cytology/*physiology ; }, abstract = {Multicellularity has evolved numerous times across the tree of life. One of the most fundamental distinctions among multicellular organisms is their developmental mode: whether they stay together during growth and develop clonally, or form a group through the aggregation of free-living cells. The five eukaryotic lineages to independently evolve complex multicellularity (animals, plants, red algae, brown algae, and fungi) all develop clonally. This fact has largely been explained through social evolutionary theory's lens of cooperation and conflict, where cheating within non-clonal groups has the potential to undermine multicellular adaptation. Multicellular organisms that form groups via aggregation could mitigate the costs of cheating by evolving kin recognition systems that prevent the formation of chimeric groups. However, recent work suggests that selection for the ability to aggregate quickly may constrain the evolution of highly specific kin recognition, sowing the seeds for persistent evolutionary conflict. Importantly, other features of aggregative multicellular life cycles may independently act to constrain the evolution of complex multicellularity. All known aggregative multicellular organisms are facultatively multicellular (as opposed to obligately multicellular), allowing unicellular-level adaptation to environmental selection. Because they primarily exist in a unicellular state, it may be difficult for aggregative multicellular organisms to evolve multicellular traits that carry pleiotropic cell-level fitness costs. Thus, even in the absence of social conflict, aggregative multicellular organisms may have limited potential for the evolution of complex multicellularity.}, } @article {pmid34102596, year = {2021}, author = {Amaral-Zettler, LA and Zettler, ER and Mincer, TJ and Klaassen, MA and Gallager, SM}, title = {Biofouling impacts on polyethylene density and sinking in coastal waters: A macro/micro tipping point?.}, journal = {Water research}, volume = {201}, number = {}, pages = {117289}, doi = {10.1016/j.watres.2021.117289}, pmid = {34102596}, issn = {1879-2448}, mesh = {Animals ; *Biofouling ; Environmental Monitoring ; North Sea ; Plastics ; Polyethylene ; *Water Pollutants, Chemical/analysis ; }, abstract = {Biofouling causing an increase in plastic density and sinking is one of the hypotheses to account for the unexpectedly low amount of buoyant plastic debris encountered at the ocean surface. Field surveys show that polyethylene and polypropylene, the two most abundant buoyant plastics, both occur below the surface and in sediments, and experimental studies confirm that biofouling can cause both of these plastics to sink. However, studies quantifying the actual density of fouled plastics are rare, despite the fact that density will determine the transport and eventual fate of plastic in the ocean. Here we investigated the role of microbial biofilms in sinking of polyethylene microplastic and quantified the density changes natural biofouling communities cause in the coastal waters of the North Sea. Molecular data confirmed the variety of bacteria and eukaryotes (including animals and other multicellular organisms) colonizing the plastic over time. Fouling communities increased the density of plastic and caused sinking, and the plastic remained negatively buoyant even during the winter with lower growth rates. Relative surface area alone, however, did not predict whether a plastic piece sank. Due to patchy colonization, fragmentation of sinking pieces may result in smaller pieces regaining buoyancy and returning to the surface. Our results suggest that primarily multicellular organisms cause sinking of plastic pieces with surface area to volume ratios (SA:V) below 100 (generally pieces above a couple hundred micrometers in size), and that this is a "tipping point" at which microbial biofilms become the key players causing sinking of smaller pieces with higher SA:V ratios, including most fibers that are too small for larger (multicellular) organisms to colonize.}, } @article {pmid34102232, year = {2021}, author = {Torday, JS}, title = {Cellular evolution of language.}, journal = {Progress in biophysics and molecular biology}, volume = {167}, number = {}, pages = {140-146}, doi = {10.1016/j.pbiomolbio.2021.05.009}, pmid = {34102232}, issn = {1873-1732}, mesh = {Animals ; *Biological Evolution ; Humans ; *Language ; Phenotype ; }, abstract = {The evolutionary origin of language remains unknown despite many efforts to determine the origin of this signature human trait. Based on epigenetic inheritance, the current article hypothesizes that language evolved from cell-cell communication as the basis for generating structure and function embryologically and phylogenetically, as did all physiologic traits. Beginning with lipids forming the first micelle, a vertical integration of the evolved properties of the cell, from multicellular organisms to the introduction of cholesterol into the cell membrane, to the evolution of the peroxisome, the water-land transition and duplication of the βAdrenergic Receptor, the evolution of endothermy, leading to bipedalism, freeing the forelimbs for toolmaking and language, selection pressure for myelinization of the central nervous system to facilitate calcium flux, bespeaks human expression, culminating in the evolution of civilization. This process is epitomized by the Area of Broca as the structural-functional site for both motor control and language formation. The mechanistic interrelationship between motor control and language formation is underscored by the role of FoxP2 gene expression in both bipedalism and language. The effect of endothermy on bipedalism, freeing the forelimbs for toolmaking and language as the vertical integration from Cosmology to Physiology as the basis for language bespeaks human expression.}, } @article {pmid34097041, year = {2021}, author = {Li, Y and Shen, XX and Evans, B and Dunn, CW and Rokas, A}, title = {Rooting the Animal Tree of Life.}, journal = {Molecular biology and evolution}, volume = {38}, number = {10}, pages = {4322-4333}, pmid = {34097041}, issn = {1537-1719}, support = {R56 AI146096/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; *Ctenophora ; Phylogeny ; }, abstract = {Identifying our most distant animal relatives has emerged as one of the most challenging problems in phylogenetics. This debate has major implications for our understanding of the origin of multicellular animals and of the earliest events in animal evolution, including the origin of the nervous system. Some analyses identify sponges as our most distant animal relatives (Porifera-sister hypothesis), and others identify comb jellies (Ctenophora-sister hypothesis). These analyses vary in many respects, making it difficult to interpret previous tests of these hypotheses. To gain insight into why different studies yield different results, an important next step in the ongoing debate, we systematically test these hypotheses by synthesizing 15 previous phylogenomic studies and performing new standardized analyses under consistent conditions with additional models. We find that Ctenophora-sister is recovered across the full range of examined conditions, and Porifera-sister is recovered in some analyses under narrow conditions when most outgroups are excluded and site-heterogeneous CAT models are used. We additionally find that the number of categories in site-heterogeneous models is sufficient to explain the Porifera-sister results. Furthermore, our cross-validation analyses show CAT models that recover Porifera-sister have hundreds of additional categories and fail to fit significantly better than site-heterogenuous models with far fewer categories. Systematic and standardized testing of diverse phylogenetic models suggests that we should be skeptical of Porifera-sister results both because they are recovered under such narrow conditions and because the models in these conditions fit the data no better than other models that recover Ctenophora-sister.}, } @article {pmid34077702, year = {2021}, author = {Kang, S and Tice, AK and Stairs, CW and Jones, RE and Lahr, DJG and Brown, MW}, title = {The integrin-mediated adhesive complex in the ancestor of animals, fungi, and amoebae.}, journal = {Current biology : CB}, volume = {31}, number = {14}, pages = {3073-3085.e3}, doi = {10.1016/j.cub.2021.04.076}, pmid = {34077702}, issn = {1879-0445}, support = {MOP-142349//CIHR/Canada ; }, mesh = {Amoeba ; Animals ; *Cell Adhesion ; *Eukaryota ; Evolution, Molecular ; Fungi ; *Integrins ; Phylogeny ; }, abstract = {Integrins are transmembrane receptors that activate signal transduction pathways upon extracellular matrix binding. The integrin-mediated adhesive complex (IMAC) mediates various cell physiological processes. Although the IMAC was thought to be specific to animals, in the past ten years these complexes were discovered in other lineages of Obazoa, the group containing animals, fungi, and several microbial eukaryotes. Very recently, many genomes and transcriptomes from Amoebozoa (the eukaryotic supergroup sister to Obazoa), other obazoans, orphan protist lineages, and the eukaryotes' closest prokaryotic relatives, have become available. To increase the resolution of where and when IMAC proteins exist and have emerged, we surveyed these newly available genomes and transcriptomes for the presence of IMAC proteins. Our results highlight that many of these proteins appear to have evolved earlier in eukaryote evolution than previously thought and that co-option of this apparently ancient protein complex was key to the emergence of animal-type multicellularity. The role of the IMACs in amoebozoans is unknown, but they play critical adhesive roles in at least some unicellular organisms.}, } @article {pmid34076889, year = {2021}, author = {Badis, Y and Scornet, D and Harada, M and Caillard, C and Godfroy, O and Raphalen, M and Gachon, CMM and Coelho, SM and Motomura, T and Nagasato, C and Cock, JM}, title = {Targeted CRISPR-Cas9-based gene knockouts in the model brown alga Ectocarpus.}, journal = {The New phytologist}, volume = {231}, number = {5}, pages = {2077-2091}, doi = {10.1111/nph.17525}, pmid = {34076889}, issn = {1469-8137}, mesh = {Animals ; *CRISPR-Cas Systems/genetics ; Clustered Regularly Interspaced Short Palindromic Repeats ; Eukaryota ; Gene Knockout Techniques ; *Phaeophyta/genetics ; }, abstract = {Brown algae are an important group of multicellular eukaryotes, phylogenetically distinct from both the animal and land plant lineages. Ectocarpus has emerged as a model organism to study diverse aspects of brown algal biology, but this system currently lacks an effective reverse genetics methodology to analyse the functions of selected target genes. Here, we report that mutations at specific target sites are generated following the introduction of CRISPR-Cas9 ribonucleoproteins into Ectocarpus cells, using either biolistics or microinjection as the delivery method. Individuals with mutations affecting the ADENINE PHOSPHORIBOSYL TRANSFERASE (APT) gene were isolated following treatment with 2-fluoroadenine, and this selection system was used to isolate individuals in which mutations had been introduced simultaneously at APT and at a second gene. This double mutation approach could potentially be used to isolate mutants affecting any Ectocarpus gene, providing an effective reverse genetics tool for this model organism. The availability of this tool will significantly enhance the utility of Ectocarpus as a model organism for this ecologically and economically important group of marine organisms. Moreover, the methodology described here should be readily transferable to other brown algal species.}, } @article {pmid34066959, year = {2021}, author = {Miller, WB and Enguita, FJ and Leitão, AL}, title = {Non-Random Genome Editing and Natural Cellular Engineering in Cognition-Based Evolution.}, journal = {Cells}, volume = {10}, number = {5}, pages = {}, pmid = {34066959}, issn = {2073-4409}, mesh = {Animals ; *Biological Evolution ; *Cell Engineering ; Cognition/*physiology ; *Gene Editing ; *Homeostasis ; Humans ; *Selection, Genetic ; }, abstract = {Neo-Darwinism presumes that biological variation is a product of random genetic replication errors and natural selection. Cognition-Based Evolution (CBE) asserts a comprehensive alternative approach to phenotypic variation and the generation of biological novelty. In CBE, evolutionary variation is the product of natural cellular engineering that permits purposive genetic adjustments as cellular problem-solving. CBE upholds that the cornerstone of biology is the intelligent measuring cell. Since all biological information that is available to cells is ambiguous, multicellularity arises from the cellular requirement to maximize the validity of available environmental information. This is best accomplished through collective measurement purposed towards maintaining and optimizing individual cellular states of homeorhesis as dynamic flux that sustains cellular equipoise. The collective action of the multicellular measurement and assessment of information and its collaborative communication is natural cellular engineering. Its yield is linked cellular ecologies and mutualized niche constructions that comprise biofilms and holobionts. In this context, biological variation is the product of collective differential assessment of ambiguous environmental cues by networking intelligent cells. Such concerted action is enabled by non-random natural genomic editing in response to epigenetic impacts and environmental stresses. Random genetic activity can be either constrained or deployed as a 'harnessing of stochasticity'. Therefore, genes are cellular tools. Selection filters cellular solutions to environmental stresses to assure continuous cellular-organismal-environmental complementarity. Since all multicellular eukaryotes are holobionts as vast assemblages of participants of each of the three cellular domains (Prokaryota, Archaea, Eukaryota) and the virome, multicellular variation is necessarily a product of co-engineering among them.}, } @article {pmid34063320, year = {2021}, author = {Mahajan, D and Kancharla, S and Kolli, P and Sharma, AK and Singh, S and Kumar, S and Mohanty, AK and Jena, MK}, title = {Role of Fibulins in Embryonic Stage Development and Their Involvement in Various Diseases.}, journal = {Biomolecules}, volume = {11}, number = {5}, pages = {}, pmid = {34063320}, issn = {2218-273X}, mesh = {Animals ; Calcium-Binding Proteins/genetics/*metabolism ; *Embryonic Development ; Extracellular Matrix/metabolism ; Gene Expression Regulation, Developmental ; Humans ; Neoplasms/*genetics/metabolism ; Protein Isoforms/metabolism ; }, abstract = {The extracellular matrix (ECM) plays an important role in the evolution of early metazoans, as it provides structural and biochemical support to the surrounding cells through the cell-cell and cell-matrix interactions. In multi-cellular organisms, ECM plays a pivotal role in the differentiation of tissues and in the development of organs. Fibulins are ECM glycoproteins, found in a variety of tissues associated with basement membranes, elastic fibers, proteoglycan aggregates, and fibronectin microfibrils. The expression profile of fibulins reveals their role in various developmental processes such as elastogenesis, development of organs during the embryonic stage, tissue remodeling, maintenance of the structural integrity of basement membrane, and elastic fibers, as well as other cellular processes. Apart from this, fibulins are also involved in the progression of human diseases such as cancer, cardiac diseases, congenital disorders, and chronic fibrotic disorders. Different isoforms of fibulins show a dual role of tumor-suppressive and tumor-promoting activities, depending on the cell type and cellular microenvironment in the body. Knockout animal models have provided deep insight into their role in development and diseases. The present review covers details of the structural and expression patterns, along with the role of fibulins in embryonic development and disease progression, with more emphasis on their involvement in the modulation of cancer diseases.}, } @article {pmid34061031, year = {2021}, author = {Kaur, G and Iyer, LM and Burroughs, AM and Aravind, L}, title = {Bacterial death and TRADD-N domains help define novel apoptosis and immunity mechanisms shared by prokaryotes and metazoans.}, journal = {eLife}, volume = {10}, number = {}, pages = {}, pmid = {34061031}, issn = {2050-084X}, support = {F38 LM000084/LM/NLM NIH HHS/United States ; Z01 LM000084/ImNIH/Intramural NIH HHS/United States ; }, mesh = {*Apoptosis ; Bacteria/genetics/immunology/*metabolism ; Bacterial Proteins/genetics/immunology/*metabolism ; *Death Domain Superfamily ; Evolution, Molecular ; Genomics ; Host-Pathogen Interactions ; Microbial Viability ; Phylogeny ; Prokaryotic Cells/immunology/*metabolism ; Signal Transduction ; Symbiosis ; TNF Receptor-Associated Death Domain Protein/genetics/immunology/*metabolism ; }, abstract = {Several homologous domains are shared by eukaryotic immunity and programmed cell-death systems and poorly understood bacterial proteins. Recent studies show these to be components of a network of highly regulated systems connecting apoptotic processes to counter-invader immunity, in prokaryotes with a multicellular habit. However, the provenance of key adaptor domains, namely those of the Death-like and TRADD-N superfamilies, a quintessential feature of metazoan apoptotic systems, remained murky. Here, we use sensitive sequence analysis and comparative genomics methods to identify unambiguous bacterial homologs of the Death-like and TRADD-N superfamilies. We show the former to have arisen as part of a radiation of effector-associated α-helical adaptor domains that likely mediate homotypic interactions bringing together diverse effector and signaling domains in predicted bacterial apoptosis- and counter-invader systems. Similarly, we show that the TRADD-N domain defines a key, widespread signaling bridge that links effector deployment to invader-sensing in multicellular bacterial and metazoan counter-invader systems. TRADD-N domains are expanded in aggregating marine invertebrates and point to distinctive diversifying immune strategies probably directed both at RNA and retroviruses and cellular pathogens that might infect such communities. These TRADD-N and Death-like domains helped identify several new bacterial and metazoan counter-invader systems featuring underappreciated, common functional principles: the use of intracellular invader-sensing lectin-like (NPCBM and FGS), transcription elongation GreA/B-C, glycosyltransferase-4 family, inactive NTPase (serving as nucleic acid receptors), and invader-sensing GTPase switch domains. Finally, these findings point to the possibility of multicellular bacteria-stem metazoan symbiosis in the emergence of the immune/apoptotic systems of the latter.}, } @article {pmid34052880, year = {2022}, author = {Fernández, LD and Seppey, CVW and Singer, D and Fournier, B and Tatti, D and Mitchell, EAD and Lara, E}, title = {Niche Conservatism Drives the Elevational Diversity Gradient in Major Groups of Free-Living Soil Unicellular Eukaryotes.}, journal = {Microbial ecology}, volume = {83}, number = {2}, pages = {459-469}, pmid = {34052880}, issn = {1432-184X}, mesh = {Biodiversity ; *Ciliophora/genetics ; Ecosystem ; Phylogeny ; *Soil ; }, abstract = {Ancestral adaptations to tropical-like climates drive most multicellular biogeography and macroecology. Observational studies suggest that this niche conservatism could also be shaping unicellular biogeography and macroecology, although evidence is limited to Acidobacteria and testate amoebae. We tracked the phylogenetic signal of this niche conservatism in far related and functionally contrasted groups of common soil protists (Bacillariophyta, Cercomonadida, Ciliophora, Euglyphida and Kinetoplastida) along a humid but increasingly cold elevational gradient in Switzerland. Protist diversity decreased, and the size of the geographic ranges of taxa increased with elevation and associated decreasing temperature (climate), which is consistent with a macroecological pattern known as the Rapoport effect. Bacillariophyta exhibited phylogenetically overdispersed communities assembled by competitive exclusion of closely related taxa with shared (conserved) niches. By contrast, Cercomonadida, Ciliophora, Euglyphida and Kinetoplastida exhibited phylogenetically clustered communities assembled by habitat filtering, revealing the coexistence of closely related taxa with shared (conserved) adaptations to cope with the humid but temperate to cold climate of the study site. Phylobetadiversity revealed that soil protists exhibit a strong phylogenetic turnover among elevational sites, suggesting that most taxa have evolutionary constraints that prevent them from colonizing the colder and higher sites of the elevation gradient. Our results suggest that evolutionary constraints determine how soil protists colonize climates departing from warm and humid conditions. We posit that these evolutionary constraints are linked to an ancestral adaptation to tropical-like climates, which limits their survival in exceedingly cold sites. This niche conservatism possibly drives their biogeography and macroecology along latitudinal and altitudinal climatic gradients.}, } @article {pmid34050941, year = {2021}, author = {Grandhi, TSP and To, J and Romero, A and Luna, F and Barnes, W and Walker, J and Moran, R and Newlin, R and Miraglia, L and Orth, AP and Horman, SR}, title = {High-throughput CRISPR-mediated 3D enrichment platform for functional interrogation of chemotherapeutic resistance.}, journal = {Biotechnology and bioengineering}, volume = {118}, number = {8}, pages = {3187-3199}, doi = {10.1002/bit.27844}, pmid = {34050941}, issn = {1097-0290}, mesh = {Antineoplastic Agents/*pharmacology ; *Breast Neoplasms/drug therapy/genetics/metabolism ; *CRISPR-Cas Systems ; *Cell Culture Techniques ; Cell Line, Tumor ; *Drug Resistance, Neoplasm ; Drug Screening Assays, Antitumor ; Female ; Humans ; Spheroids, Cellular/*metabolism ; *Tumor Microenvironment ; }, abstract = {Cancer is a disease of somatic mutations. These cellular mutations compete to dominate their microenvironment and dictate the disease outcome. While a therapeutic approach to target-specific oncogenic driver mutations helps to manage the disease, subsequent molecular evolution of tumor cells threatens to overtake therapeutic progress. There is a need for rapid, high-throughput, unbiased in vitro discovery screening platforms that capture the native complexities of the tumor and rapidly identify mutations that confer chemotherapeutic drug resistance. Taking the example of the CDK4/6 inhibitor (CDK4/6i) class of drugs, we show that the pooled in vitro CRISPR screening platform enables rapid discovery of drug resistance mutations in a three-dimensional (3D) setting. Gene-edited cancer cell clones assembled into an organotypic multicellular tumor spheroid (MCTS), exposed to CDK4/6i caused selection and enrichment of the most drug-resistant phenotypes, detectable by next-gen sequencing after a span of 28 days. The platform was sufficiently sensitive to enrich for even a single drug-resistant cell within a large, drug-responsive complex 3D tumor spheroid. The genome-wide 3D CRISPR-mediated knockout screen (>18,000 genes) identified several genes whose disruptions conferred resistance to CDK4/6i. Furthermore, multiple novel candidate genes were identified as top hits only in the microphysiological 3D enrichment assay platform and not the conventional 2D assays. Taken together, these findings suggest that including phenotypic 3D resistance profiling in decision trees could improve discovery and reconfirmation of drug resistance mechanisms and afford a platform for exploring noncell autonomous interactions, selection pressures, and clonal competition.}, } @article {pmid34047647, year = {2021}, author = {Sheng, Y and Pan, B and Wei, F and Wang, Y and Gao, S}, title = {Case Study of the Response of N[6]-Methyladenine DNA Modification to Environmental Stressors in the Unicellular Eukaryote Tetrahymena thermophila.}, journal = {mSphere}, volume = {6}, number = {3}, pages = {e0120820}, pmid = {34047647}, issn = {2379-5042}, mesh = {Adenine/*analogs & derivatives/pharmacology ; Epigenesis, Genetic ; Genome, Protozoan ; Methylation ; Protein Processing, Post-Translational ; Stress, Physiological/*drug effects/genetics ; Tetrahymena thermophila/*drug effects/*genetics/metabolism ; }, abstract = {Rediscovered as a potential epigenetic mark, N[6]-methyladenine DNA modification (6mA) was recently reported to be sensitive to environmental stressors in several multicellular eukaryotes. As 6mA distribution and function differ significantly in multicellular and unicellular organisms, whether and how 6mA in unicellular eukaryotes responds to environmental stress remains elusive. Here, we characterized the dynamic changes of 6mA under starvation in the unicellular model organism Tetrahymena thermophila. Single-molecule, real-time (SMRT) sequencing reveals that DNA 6mA levels in starved cells are significantly reduced, especially symmetric 6mA, compared to those in vegetatively growing cells. Despite a global 6mA reduction, the fraction of asymmetric 6mA with a high methylation level was increased, which might be the driving force for stronger nucleosome positioning in starved cells. Starvation affects expression of many metabolism-related genes, the expression level change of which is associated with the amount of 6mA change, thereby linking 6mA with global transcription and starvation adaptation. The reduction of symmetric 6mA and the increase of asymmetric 6mA coincide with the downregulation of AMT1 and upregulation of AMT2 and AMT5, which are supposedly the MT-A70 methyltransferases required for symmetric and asymmetric 6mA, respectively. These results demonstrated that a regulated 6mA response to environmental cues is evolutionarily conserved in eukaryotes. IMPORTANCE Increasing evidence indicated that 6mA could respond to environmental stressors in multicellular eukaryotes. As 6mA distribution and function differ significantly in multicellular and unicellular organisms, whether and how 6mA in unicellular eukaryotes responds to environmental stress remains elusive. In the present work, we characterized the dynamic changes of 6mA under starvation in the unicellular model organism Tetrahymena thermophila. Our results provide insights into how Tetrahymena fine-tunes its 6mA level and composition upon starvation, suggesting that a regulated 6mA response to environmental cues is evolutionarily conserved in eukaryotes.}, } @article {pmid34031540, year = {2021}, author = {Kumari, P and Dahiya, P and Livanos, P and Zergiebel, L and Kölling, M and Poeschl, Y and Stamm, G and Hermann, A and Abel, S and Müller, S and Bürstenbinder, K}, title = {IQ67 DOMAIN proteins facilitate preprophase band formation and division-plane orientation.}, journal = {Nature plants}, volume = {7}, number = {6}, pages = {739-747}, pmid = {34031540}, issn = {2055-0278}, mesh = {Arabidopsis/*cytology/genetics ; Arabidopsis Proteins/genetics/*metabolism ; Dinitrobenzenes ; Gene Expression Regulation, Plant ; Green Fluorescent Proteins/genetics/metabolism ; Microtubules/drug effects/metabolism ; Mutation ; Phylogeny ; Plant Cells/drug effects/metabolism ; Plants, Genetically Modified ; Prophase ; Protein Domains ; Sulfanilamides ; Tobacco/genetics ; Vesicular Transport Proteins/metabolism ; }, abstract = {Spatiotemporal control of cell division is essential for the growth and development of multicellular organisms. In plant cells, proper cell plate insertion during cytokinesis relies on the premitotic establishment of the division plane at the cell cortex. Two plant-specific cytoskeleton arrays, the preprophase band (PPB) and the phragmoplast, play important roles in division-plane orientation and cell plate formation, respectively[1]. Microtubule organization and dynamics and their communication with membranes at the cortex and cell plate are coordinated by multiple, mostly distinct microtubule-associated proteins[2]. How division-plane selection and establishment are linked, however, is still unknown. Here, we report members of the Arabidopsis IQ67 DOMAIN (IQD) family[3] as microtubule-targeted proteins that localize to the PPB and phragmoplast and additionally reside at the cell plate and a polarized cortical region including the cortical division zone (CDZ). IQDs physically interact with PHRAGMOPLAST ORIENTING KINESIN (POK) proteins[4,5] and PLECKSTRIN HOMOLOGY GTPase ACTIVATING (PHGAP) proteins[6], which are core components of the CDZ[1]. The loss of IQD function impairs PPB formation and affects CDZ recruitment of POKs and PHGAPs, resulting in division-plane positioning defects. We propose that IQDs act as cellular scaffolds that facilitate PPB formation and CDZ set-up during symmetric cell division.}, } @article {pmid34026448, year = {2021}, author = {Jiang, S and Li, H and Zeng, Q and Xiao, Z and Zhang, X and Xu, M and He, Y and Wei, Y and Deng, X}, title = {The Dynamic Counterbalance of RAC1-YAP/OB-Cadherin Coordinates Tissue Spreading with Stem Cell Fate Patterning.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {8}, number = {10}, pages = {2004000}, pmid = {34026448}, issn = {2198-3844}, mesh = {Animals ; Cadherins/*metabolism ; Cell Adhesion/physiology ; Cell Differentiation/physiology ; Cell Lineage ; Cell Movement/physiology ; Cells, Cultured ; Mesenchymal Stem Cells/cytology/*metabolism ; Mice ; Models, Animal ; Morphogenesis ; Signal Transduction ; YAP-Signaling Proteins/*metabolism ; rac1 GTP-Binding Protein/*metabolism ; }, abstract = {Tissue spreading represents a key morphogenetic feature of embryonic development and regenerative medicine. However, how molecular signaling orchestrates the spreading dynamics and cell fate commitment of multicellular tissue remains poorly understood. Here, it is demonstrated that the dynamic counterbalance between RAC1-YAP and OB-cadherin plays a key role in coordinating heterogeneous spreading dynamics with distinct cell fate patterning during collective spreading. The spatiotemporal evolution of individual stem cells in spheroids during collective spreading is mapped. Time-lapse cell migratory trajectory analysis combined with in situ cellular biomechanics detection reveal heterogeneous patterns of collective spreading characteristics, where the cells at the periphery are faster, stiffer, and directional compared to those in the center of the spheroid. Single-cell sequencing shows that the divergent spreading result in distinct cell fate patterning, where differentiation, proliferation, and metabolism are enhanced in peripheral cells. Molecular analysis demonstrates that the increased expression of RAC1-YAP rather than OB-cadherin facilitated cell spreading and induced differentiation, and vice versa. The in vivo wound healing experiment confirms the functional role of RAC1-YAP signaling in tissue spreading. These findings shed light on the mechanism of tissue morphogenesis in the progression of development and provide a practical strategy for desirable regenerative therapies.}, } @article {pmid34023299, year = {2021}, author = {Schneider, P and Reece, SE}, title = {The private life of malaria parasites: Strategies for sexual reproduction.}, journal = {Molecular and biochemical parasitology}, volume = {244}, number = {}, pages = {111375}, pmid = {34023299}, issn = {1872-9428}, support = {202769/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Biological Coevolution ; Culicidae/parasitology ; Erythrocytes/parasitology ; Female ; *Gametogenesis ; Host-Parasite Interactions/genetics ; Humans ; Insect Vectors/parasitology ; Life Cycle Stages/*genetics ; Liver/parasitology ; Malaria/*parasitology/transmission ; Male ; Plasmodium berghei/genetics/*growth & development/metabolism ; Plasmodium chabaudi/genetics/*growth & development/metabolism ; Plasmodium falciparum/genetics/*growth & development/metabolism ; Plasmodium knowlesi/genetics/*growth & development/metabolism ; Reproduction, Asexual ; Sex Ratio ; }, abstract = {Malaria parasites exhibit a complex lifecycle, requiring extensive asexual replication in the liver and blood of the vertebrate host, and in the haemocoel of the insect vector. Yet, they must also undergo a single round of sexual reproduction, which occurs in the vector's midgut upon uptake of a blood meal. Sexual reproduction is obligate for infection of the vector and thus, is essential for onwards transmission to new hosts. Sex in malaria parasites involves several bottlenecks in parasite number, making the stages involved attractive targets for blocking disease transmission. Malaria parasites have evolved a suite of adaptations ("strategies") to maximise the success of sexual reproduction and transmission, which could undermine transmission-blocking interventions. Yet, understanding parasite strategies may also reveal novel opportunities for such interventions. Here, we outline how evolutionary and ecological theories, developed to explain reproductive strategies in multicellular taxa, can be applied to explain two reproductive strategies (conversion rate and sex ratio) expressed by malaria parasites within the vertebrate host.}, } @article {pmid34020820, year = {2021}, author = {Tanay, A and Sebé-Pedrós, A}, title = {Evolutionary cell type mapping with single-cell genomics.}, journal = {Trends in genetics : TIG}, volume = {37}, number = {10}, pages = {919-932}, doi = {10.1016/j.tig.2021.04.008}, pmid = {34020820}, issn = {0168-9525}, mesh = {Animals ; Cells/*classification/*metabolism ; *Evolution, Molecular ; Genome/*genetics ; *Genomics ; Humans ; Organ Specificity ; *Single-Cell Analysis ; }, abstract = {A fundamental characteristic of animal multicellularity is the spatial coexistence of functionally specialized cell types that are all encoded by a single genome sequence. Cell type transcriptional programs are deployed and maintained by regulatory mechanisms that control the asymmetric, differential access to genomic information in each cell. This genome regulation ultimately results in specific cellular phenotypes. However, the emergence, diversity, and evolutionary dynamics of animal cell types remain almost completely unexplored beyond a few species. Single-cell genomics is emerging as a powerful tool to build comprehensive catalogs of cell types and their associated gene regulatory programs in non-traditional model species. We review the current state of sampling efforts across the animal tree of life and challenges ahead for the comparative study of cell type programs. We also discuss how the phylogenetic integration of cell atlases can lead to the development of models of cell type evolution and a phylogenetic taxonomy of cells.}, } @article {pmid34007033, year = {2021}, author = {Maier, BA and Kiefer, P and Field, CM and Hemmerle, L and Bortfeld-Miller, M and Emmenegger, B and Schäfer, M and Pfeilmeier, S and Sunagawa, S and Vogel, CM and Vorholt, JA}, title = {A general non-self response as part of plant immunity.}, journal = {Nature plants}, volume = {7}, number = {5}, pages = {696-705}, pmid = {34007033}, issn = {2055-0278}, support = {668991/ERC_/European Research Council/International ; }, mesh = {Arabidopsis/*immunology/microbiology/physiology ; Bacteria/genetics/immunology ; Gene Expression Regulation, Plant ; Genes, Plant/immunology/physiology ; Metabolome ; Phylogeny ; Plant Diseases/immunology/microbiology ; Plant Immunity/genetics/physiology ; Secondary Metabolism ; Tryptophan/metabolism ; }, abstract = {Plants, like other multicellular lifeforms, are colonized by microorganisms. How plants respond to their microbiota is currently not well understood. We used a phylogenetically diverse set of 39 endogenous bacterial strains from Arabidopsis thaliana leaves to assess host transcriptional and metabolic adaptations to bacterial encounters. We identified a molecular response, which we termed the general non-self response (GNSR) that involves the expression of a core set of 24 genes. The GNSR genes are not only consistently induced by the presence of most strains, they also comprise the most differentially regulated genes across treatments and are predictive of a hierarchical transcriptional reprogramming beyond the GNSR. Using a complementary untargeted metabolomics approach we link the GNSR to the tryptophan-derived secondary metabolism, highlighting the importance of small molecules in plant-microbe interactions. We demonstrate that several of the GNSR genes are required for resistance against the bacterial pathogen Pseudomonas syringae. Our results suggest that the GNSR constitutes a defence adaptation strategy that is consistently elicited by diverse strains from various phyla, contributes to host protection and involves secondary metabolism.}, } @article {pmid33990594, year = {2021}, author = {Bozdag, GO and Libby, E and Pineau, R and Reinhard, CT and Ratcliff, WC}, title = {Oxygen suppression of macroscopic multicellularity.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {2838}, pmid = {33990594}, issn = {2041-1723}, mesh = {Aerobiosis ; Anaerobiosis ; *Biological Evolution ; Biophysical Phenomena ; DNA-Binding Proteins/genetics ; Directed Molecular Evolution ; Eukaryotic Cells/*cytology/*metabolism ; Gene Deletion ; Genetic Engineering ; *Models, Biological ; Oxygen/*metabolism ; Saccharomyces cerevisiae/*cytology/genetics/*metabolism ; Saccharomyces cerevisiae Proteins/genetics ; Selection, Genetic ; Synthetic Biology ; Transcription Factors/genetics ; }, abstract = {Atmospheric oxygen is thought to have played a vital role in the evolution of large, complex multicellular organisms. Challenging the prevailing theory, we show that the transition from an anaerobic to an aerobic world can strongly suppress the evolution of macroscopic multicellularity. Here we select for increased size in multicellular 'snowflake' yeast across a range of metabolically-available O2 levels. While yeast under anaerobic and high-O2 conditions evolved to be considerably larger, intermediate O2 constrained the evolution of large size. Through sequencing and synthetic strain construction, we confirm that this is due to O2-mediated divergent selection acting on organism size. We show via mathematical modeling that our results stem from nearly universal evolutionary and biophysical trade-offs, and thus should apply broadly. These results highlight the fact that oxygen is a double-edged sword: while it provides significant metabolic advantages, selection for efficient use of this resource may paradoxically suppress the evolution of macroscopic multicellular organisms.}, } @article {pmid33988501, year = {2021}, author = {Lu, YX and Regan, JC and Eßer, J and Drews, LF and Weinseis, T and Stinn, J and Hahn, O and Miller, RA and Grönke, S and Partridge, L}, title = {A TORC1-histone axis regulates chromatin organisation and non-canonical induction of autophagy to ameliorate ageing.}, journal = {eLife}, volume = {10}, number = {}, pages = {}, pmid = {33988501}, issn = {2050-084X}, support = {P30 AG024824/AG/NIA NIH HHS/United States ; P40 OD018537/OD/NIH HHS/United States ; U01 AG022303/AG/NIA NIH HHS/United States ; U19 AG023122/AG/NIA NIH HHS/United States ; }, mesh = {Aging/*drug effects/metabolism ; Animals ; *Autophagy ; Chromatin/metabolism ; Drosophila melanogaster ; Eukaryotic Initiation Factor-3/metabolism ; Female ; Gene Expression Regulation ; Histones/genetics/*metabolism ; Intestines ; Mechanistic Target of Rapamycin Complex 1/genetics/*metabolism ; Mice ; Sirolimus/pharmacology ; }, abstract = {Age-related changes to histone levels are seen in many species. However, it is unclear whether changes to histone expression could be exploited to ameliorate the effects of ageing in multicellular organisms. Here we show that inhibition of mTORC1 by the lifespan-extending drug rapamycin increases expression of histones H3 and H4 post-transcriptionally through eIF3-mediated translation. Elevated expression of H3/H4 in intestinal enterocytes in Drosophila alters chromatin organisation, induces intestinal autophagy through transcriptional regulation, and prevents age-related decline in the intestine. Importantly, it also mediates rapamycin-induced longevity and intestinal health. Histones H3/H4 regulate expression of an autophagy cargo adaptor Bchs (WDFY3 in mammals), increased expression of which in enterocytes mediates increased H3/H4-dependent healthy longevity. In mice, rapamycin treatment increases expression of histone proteins and Wdfy3 transcription, and alters chromatin organisation in the small intestine, suggesting that the mTORC1-histone axis is at least partially conserved in mammals and may offer new targets for anti-ageing interventions.}, } @article {pmid33984158, year = {2021}, author = {Lineweaver, CH and Bussey, KJ and Blackburn, AC and Davies, PCW}, title = {Cancer progression as a sequence of atavistic reversions.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {43}, number = {7}, pages = {e2000305}, pmid = {33984158}, issn = {1521-1878}, support = {U54 CA217376/CA/NCI NIH HHS/United States ; U54-CA143682/CA/NCI NIH HHS/United States ; }, mesh = {*Biological Evolution ; Eukaryota ; Eukaryotic Cells ; Humans ; *Neoplasms/genetics ; Phenotype ; }, abstract = {It has long been recognized that cancer onset and progression represent a type of reversion to an ancestral quasi-unicellular phenotype. This general concept has been refined into the atavistic model of cancer that attempts to provide a quantitative analysis and testable predictions based on genomic data. Over the past decade, support for the multicellular-to-unicellular reversion predicted by the atavism model has come from phylostratigraphy. Here, we propose that cancer onset and progression involve more than a one-off multicellular-to-unicellular reversion, and are better described as a series of reversionary transitions. We make new predictions based on the chronology of the unicellular-eukaryote-to-multicellular-eukaryote transition. We also make new predictions based on three other evolutionary transitions that occurred in our lineage: eukaryogenesis, oxidative phosphorylation and the transition to adaptive immunity. We propose several modifications to current phylostratigraphy to improve age resolution to test these predictions. Also see the video abstract here: https://youtu.be/3unEu5JYJrQ.}, } @article {pmid33983920, year = {2021}, author = {van Gestel, J and Wagner, A}, title = {Cryptic surface-associated multicellularity emerges through cell adhesion and its regulation.}, journal = {PLoS biology}, volume = {19}, number = {5}, pages = {e3001250}, pmid = {33983920}, issn = {1545-7885}, mesh = {Animals ; Bacteria/metabolism ; Bacterial Adhesion/*physiology ; Biological Evolution ; Cell Adhesion/*physiology ; Cell Communication/physiology ; Cell Polarity/physiology ; Evolution, Molecular ; Fungi/metabolism ; Humans ; }, abstract = {The repeated evolution of multicellularity led to a wide diversity of organisms, many of which are sessile, including land plants, many fungi, and colonial animals. Sessile organisms adhere to a surface for most of their lives, where they grow and compete for space. Despite the prevalence of surface-associated multicellularity, little is known about its evolutionary origin. Here, we introduce a novel theoretical approach, based on spatial lineage tracking of cells, to study this origin. We show that multicellularity can rapidly evolve from two widespread cellular properties: cell adhesion and the regulatory control of adhesion. By evolving adhesion, cells attach to a surface, where they spontaneously give rise to primitive cell collectives that differ in size, life span, and mode of propagation. Selection in favor of large collectives increases the fraction of adhesive cells until a surface becomes fully occupied. Through kin recognition, collectives then evolve a central-peripheral polarity in cell adhesion that supports a division of labor between cells and profoundly impacts growth. Despite this spatial organization, nascent collectives remain cryptic, lack well-defined boundaries, and would require experimental lineage tracking technologies for their identification. Our results suggest that cryptic multicellularity could readily evolve and originate well before multicellular individuals become morphologically evident.}, } @article {pmid33979602, year = {2021}, author = {Joy, DA and Libby, ARG and McDevitt, TC}, title = {Deep neural net tracking of human pluripotent stem cells reveals intrinsic behaviors directing morphogenesis.}, journal = {Stem cell reports}, volume = {16}, number = {5}, pages = {1317-1330}, pmid = {33979602}, issn = {2213-6711}, support = {T32 HD007470/HD/NICHD NIH HHS/United States ; }, mesh = {Bone Morphogenetic Protein 4/pharmacology ; Cell Count ; Cell Differentiation/drug effects ; Cell Lineage/drug effects ; Cell Movement/drug effects ; Cell Tracking ; Cells, Cultured ; Humans ; Image Processing, Computer-Assisted ; Induced Pluripotent Stem Cells/*cytology/drug effects ; *Morphogenesis/drug effects ; *Neural Networks, Computer ; Smad Proteins/metabolism ; }, abstract = {Lineage tracing is a powerful tool in developmental biology to interrogate the evolution of tissue formation, but the dense, three-dimensional nature of tissue limits the assembly of individual cell trajectories into complete reconstructions of development. Human induced pluripotent stem cells (hiPSCs) can recapitulate aspects of developmental processes, providing an in vitro platform to assess the dynamic collective behaviors directing tissue morphogenesis. Here, we trained an ensemble of neural networks to track individual hiPSCs in time-lapse microscopy, generating longitudinal measures of cell and cellular neighborhood properties on timescales from minutes to days. Our analysis reveals that, while individual cell parameters are not strongly affected by pluripotency maintenance conditions or morphogenic cues, regional changes in cell behavior predict cell fate and colony organization. By generating complete multicellular reconstructions of hiPSC behavior, our tracking pipeline enables fine-grained understanding of morphogenesis by elucidating the role of regional behavior in early tissue formation.}, } @article {pmid33972551, year = {2021}, author = {Tsutsui, K and Machida, H and Nakagawa, A and Ahn, K and Morita, R and Sekiguchi, K and Miner, JH and Fujiwara, H}, title = {Mapping the molecular and structural specialization of the skin basement membrane for inter-tissue interactions.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {2577}, pmid = {33972551}, issn = {2041-1723}, support = {R01 DK078314/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Basement Membrane/*cytology/metabolism/ultrastructure ; Epithelial Cells/metabolism ; Extracellular Matrix/genetics/*metabolism ; Female ; Fibroblasts/metabolism ; Hair Follicle/*metabolism ; Immunohistochemistry ; Laminin/*metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Microscopy, Electron, Transmission ; Multigene Family ; Muscle Cells/metabolism ; Neurons/metabolism ; Single-Cell Analysis ; Transcriptome/*genetics ; }, abstract = {Inter-tissue interaction is fundamental to multicellularity. Although the basement membrane (BM) is located at tissue interfaces, its mode of action in inter-tissue interactions remains poorly understood, mainly because the molecular and structural details of the BM at distinct inter-tissue interfaces remain unclear. By combining quantitative transcriptomics and immunohistochemistry, we systematically identify the cellular origin, molecular identity and tissue distribution of extracellular matrix molecules in mouse hair follicles, and reveal that BM composition and architecture are exquisitely specialized for distinct inter-tissue interactions, including epithelial-fibroblast, epithelial-muscle and epithelial-nerve interactions. The epithelial-fibroblast interface, namely, hair germ-dermal papilla interface, makes asymmetrically organized side-specific heterogeneity in the BM, defined by the newly characterized interface, hook and mesh BMs. One component of these BMs, laminin α5, is required for hair cycle regulation and hair germ-dermal papilla anchoring. Our study highlights the significance of BM heterogeneity in distinct inter-tissue interactions.}, } @article {pmid33961843, year = {2021}, author = {Levin, M}, title = {Bioelectrical approaches to cancer as a problem of the scaling of the cellular self.}, journal = {Progress in biophysics and molecular biology}, volume = {165}, number = {}, pages = {102-113}, doi = {10.1016/j.pbiomolbio.2021.04.007}, pmid = {33961843}, issn = {1873-1732}, mesh = {Electrophysiological Phenomena ; Humans ; Membrane Potentials ; Morphogenesis ; *Neoplasms ; *Signal Transduction ; }, abstract = {One lens with which to understand the complex phenomenon of cancer is that of developmental biology. Cancer is the inevitable consequence of a breakdown of the communication that enables individual cells to join into computational networks that work towards large-scale, morphogenetic goals instead of more primitive, unicellular objectives. This perspective suggests that cancer may be a physiological disorder, not necessarily due to problems with the genetically-specified protein hardware. One aspect of morphogenetic coordination is bioelectric signaling, and indeed an abnormal bioelectric signature non-invasively reveals the site of incipient tumors in amphibian models. Functionally, a disruption of resting potential states triggers metastatic melanoma phenotypes in embryos with no genetic defects or carcinogen exposure. Conversely, optogenetic or molecular-biological modulation of bioelectric states can override powerful oncogenic mutations and prevent or normalize tumors. The bioelectrically-mediated information flows that harness cells toward body-level anatomical outcomes represent a very attractive and tractable endogenous control system, which is being targeted by emerging approaches to cancer.}, } @article {pmid33952585, year = {2021}, author = {Russo, M and Sogari, A and Bardelli, A}, title = {Adaptive Evolution: How Bacteria and Cancer Cells Survive Stressful Conditions and Drug Treatment.}, journal = {Cancer discovery}, volume = {11}, number = {8}, pages = {1886-1895}, doi = {10.1158/2159-8290.CD-20-1588}, pmid = {33952585}, issn = {2159-8290}, mesh = {*Bacteria ; *Biological Evolution ; *Homeostasis ; Humans ; *Neoplasms ; }, abstract = {Cancer is characterized by loss of the regulatory mechanisms that preserve homeostasis in multicellular organisms, such as controlled proliferation, cell-cell adhesion, and tissue differentiation. The breakdown of multicellularity rules is accompanied by activation of "selfish," unicellular-like life features, which are linked to the increased adaptability to environmental changes displayed by cancer cells. Mechanisms of stress response, resembling those observed in unicellular organisms, are actively exploited by mammalian cancer cells to boost genetic diversity and increase chances of survival under unfavorable conditions, such as lack of oxygen/nutrients or exposure to drugs. Unicellular organisms under stressful conditions (e.g., antibiotic treatment) stop replicating or slowly divide and transiently increase their mutation rates to foster diversity, a process known as adaptive mutability. Analogously, tumor cells exposed to drugs enter a persister phenotype and can reduce DNA replication fidelity, which in turn fosters genetic diversity. The implications of adaptive evolution are of relevance to understand resistance to anticancer therapies.}, } @article {pmid33947812, year = {2021}, author = {Hartl, B and Hübl, M and Kahl, G and Zöttl, A}, title = {Microswimmers learning chemotaxis with genetic algorithms.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {118}, number = {19}, pages = {}, pmid = {33947812}, issn = {1091-6490}, mesh = {Algorithms ; Animals ; Caenorhabditis elegans/physiology ; Chemotaxis/*genetics/*physiology ; Computer Simulation ; Flagella/physiology ; Learning/*physiology ; Machine Learning ; Models, Biological ; Motion ; Neural Networks, Computer ; Swimming/*physiology ; }, abstract = {Various microorganisms and some mammalian cells are able to swim in viscous fluids by performing nonreciprocal body deformations, such as rotating attached flagella or by distorting their entire body. In order to perform chemotaxis (i.e., to move toward and to stay at high concentrations of nutrients), they adapt their swimming gaits in a nontrivial manner. Here, we propose a computational model, which features autonomous shape adaptation of microswimmers moving in one dimension toward high field concentrations. As an internal decision-making machinery, we use artificial neural networks, which control the motion of the microswimmer. We present two methods to measure chemical gradients, spatial and temporal sensing, as known for swimming mammalian cells and bacteria, respectively. Using the genetic algorithm NeuroEvolution of Augmenting Topologies, surprisingly simple neural networks evolve. These networks control the shape deformations of the microswimmers and allow them to navigate in static and complex time-dependent chemical environments. By introducing noisy signal transmission in the neural network, the well-known biased run-and-tumble motion emerges. Our work demonstrates that the evolution of a simple and interpretable internal decision-making machinery coupled to the environment allows navigation in diverse chemical landscapes. These findings are of relevance for intracellular biochemical sensing mechanisms of single cells or for the simple nervous system of small multicellular organisms such as Caenorhabditis elegans.}, } @article {pmid33947439, year = {2021}, author = {Wang, SY and Pollina, EA and Wang, IH and Pino, LK and Bushnell, HL and Takashima, K and Fritsche, C and Sabin, G and Garcia, BA and Greer, PL and Greer, EL}, title = {Role of epigenetics in unicellular to multicellular transition in Dictyostelium.}, journal = {Genome biology}, volume = {22}, number = {1}, pages = {134}, pmid = {33947439}, issn = {1474-760X}, support = {DP2 AG067490/AG/NIA NIH HHS/United States ; R01 GM110174/GM/NIGMS NIH HHS/United States ; DP2 AG055947/AG/NIA NIH HHS/United States ; R00 AG043550/AG/NIA NIH HHS/United States ; T32 CA009140/CA/NCI NIH HHS/United States ; K99 AG064042/AG/NIA NIH HHS/United States ; }, mesh = {Acetylation ; Animals ; Caenorhabditis elegans/cytology ; Chromatin/metabolism ; Dictyostelium/*cytology/*genetics ; *Epigenesis, Genetic ; Gene Expression Profiling ; Histones/metabolism ; Methylation ; Schizosaccharomyces/cytology ; Transcription Factors/metabolism ; }, abstract = {BACKGROUND: The evolution of multicellularity is a critical event that remains incompletely understood. We use the social amoeba, Dictyostelium discoideum, one of the rare organisms that readily transits back and forth between both unicellular and multicellular stages, to examine the role of epigenetics in regulating multicellularity.

RESULTS: While transitioning to multicellular states, patterns of H3K4 methylation and H3K27 acetylation significantly change. By combining transcriptomics, epigenomics, chromatin accessibility, and orthologous gene analyses with other unicellular and multicellular organisms, we identify 52 conserved genes, which are specifically accessible and expressed during multicellular states. We validated that four of these genes, including the H3K27 deacetylase hdaD, are necessary and that an SMC-like gene, smcl1, is sufficient for multicellularity in Dictyostelium.

CONCLUSIONS: These results highlight the importance of epigenetics in reorganizing chromatin architecture to facilitate multicellularity in Dictyostelium discoideum and raise exciting possibilities about the role of epigenetics in the evolution of multicellularity more broadly.}, } @article {pmid33947322, year = {2021}, author = {Orban, A and Weber, A and Herzog, R and Hennicke, F and Rühl, M}, title = {Transcriptome of different fruiting stages in the cultivated mushroom Cyclocybe aegerita suggests a complex regulation of fruiting and reveals enzymes putatively involved in fungal oxylipin biosynthesis.}, journal = {BMC genomics}, volume = {22}, number = {1}, pages = {324}, pmid = {33947322}, issn = {1471-2164}, mesh = {*Agaricales/genetics ; Agrocybe ; Fruiting Bodies, Fungal/genetics ; Fungal Proteins/genetics/metabolism ; Gene Expression Regulation, Fungal ; Oxylipins ; Prospective Studies ; *Transcriptome ; }, abstract = {BACKGROUND: Cyclocybe aegerita (syn. Agrocybe aegerita) is a commercially cultivated mushroom. Its archetypal agaric morphology and its ability to undergo its whole life cycle under laboratory conditions makes this fungus a well-suited model for studying fruiting body (basidiome, basidiocarp) development. To elucidate the so far barely understood biosynthesis of fungal volatiles, alterations in the transcriptome during different developmental stages of C. aegerita were analyzed and combined with changes in the volatile profile during its different fruiting stages.

RESULTS: A transcriptomic study at seven points in time during fruiting body development of C. aegerita with seven mycelial and five fruiting body stages was conducted. Differential gene expression was observed for genes involved in fungal fruiting body formation showing interesting transcriptional patterns and correlations of these fruiting-related genes with the developmental stages. Combining transcriptome and volatilome data, enzymes putatively involved in the biosynthesis of C8 oxylipins in C. aegerita including lipoxygenases (LOXs), dioxygenases (DOXs), hydroperoxide lyases (HPLs), alcohol dehydrogenases (ADHs) and ene-reductases could be identified. Furthermore, we were able to localize the mycelium as the main source for sesquiterpenes predominant during sporulation in the headspace of C. aegerita cultures. In contrast, changes in the C8 profile detected in late stages of development are probably due to the activity of enzymes located in the fruiting bodies.

CONCLUSIONS: In this study, the combination of volatilome and transcriptome data of C. aegerita revealed interesting candidates both for functional genetics-based analysis of fruiting-related genes and for prospective enzyme characterization studies to further elucidate the so far barely understood biosynthesis of fungal C8 oxylipins.}, } @article {pmid33924996, year = {2021}, author = {Isaksson, H and Conlin, PL and Kerr, B and Ratcliff, WC and Libby, E}, title = {The Consequences of Budding versus Binary Fission on Adaptation and Aging in Primitive Multicellularity.}, journal = {Genes}, volume = {12}, number = {5}, pages = {}, pmid = {33924996}, issn = {2073-4425}, mesh = {*Adaptation, Physiological ; Aging/*genetics ; Animals ; *Cell Division ; Cellular Senescence ; *Models, Theoretical ; Mutation ; }, abstract = {Early multicellular organisms must gain adaptations to outcompete their unicellular ancestors, as well as other multicellular lineages. The tempo and mode of multicellular adaptation is influenced by many factors including the traits of individual cells. We consider how a fundamental aspect of cells, whether they reproduce via binary fission or budding, can affect the rate of adaptation in primitive multicellularity. We use mathematical models to study the spread of beneficial, growth rate mutations in unicellular populations and populations of multicellular filaments reproducing via binary fission or budding. Comparing populations once they reach carrying capacity, we find that the spread of mutations in multicellular budding populations is qualitatively distinct from the other populations and in general slower. Since budding and binary fission distribute age-accumulated damage differently, we consider the effects of cellular senescence. When growth rate decreases with cell age, we find that beneficial mutations can spread significantly faster in a multicellular budding population than its corresponding unicellular population or a population reproducing via binary fission. Our results demonstrate that basic aspects of the cell cycle can give rise to different rates of adaptation in multicellular organisms.}, } @article {pmid33923657, year = {2021}, author = {Romanova, MA and Maksimova, AI and Pawlowski, K and Voitsekhovskaja, OV}, title = {YABBY Genes in the Development and Evolution of Land Plants.}, journal = {International journal of molecular sciences}, volume = {22}, number = {8}, pages = {}, pmid = {33923657}, issn = {1422-0067}, mesh = {*Evolution, Molecular ; Gene Expression Regulation, Developmental ; Gene Expression Regulation, Plant ; Magnoliopsida/*genetics/growth & development/metabolism ; Plant Proteins/chemistry/*genetics/metabolism ; Transcription Factors/chemistry/*genetics/metabolism ; }, abstract = {Mounting evidence from genomic and transcriptomic studies suggests that most genetic networks regulating the morphogenesis of land plant sporophytes were co-opted and modified from those already present in streptophyte algae and gametophytes of bryophytes sensu lato. However, thus far, no candidate genes have been identified that could be responsible for "planation", a conversion from a three-dimensional to a two-dimensional growth pattern. According to the telome theory, "planation" was required for the genesis of the leaf blade in the course of leaf evolution. The key transcription factors responsible for leaf blade development in angiosperms are YABBY proteins, which until recently were thought to be unique for seed plants. Yet, identification of a YABBY homologue in a green alga and the recent findings of YABBY homologues in lycophytes and hornworts suggest that YABBY proteins were already present in the last common ancestor of land plants. Thus, these transcriptional factors could have been involved in "planation", which fosters our understanding of the origin of leaves. Here, we summarise the current data on functions of YABBY proteins in the vegetative and reproductive development of diverse angiosperms and gymnosperms as well as in the development of lycophytes. Furthermore, we discuss a putative role of YABBY proteins in the genesis of multicellular shoot apical meristems and in the evolution of leaves in early divergent terrestrial plants.}, } @article {pmid33880702, year = {2021}, author = {Wang, Z and Sun, X and Zhang, X and Dong, B and Yu, H}, title = {Development of a miRNA Sensor by an Inducible CRISPR-Cas9 Construct in Ciona Embryogenesis.}, journal = {Molecular biotechnology}, volume = {63}, number = {7}, pages = {613-620}, pmid = {33880702}, issn = {1559-0305}, mesh = {Animals ; CRISPR-Cas Systems ; Ciona/*embryology/genetics ; Gene Editing/*methods ; Gene Silencing ; MicroRNAs/*genetics ; RNA, Guide, Kinetoplastida/genetics ; }, abstract = {MicroRNAs (miRNAs) regulate multicellular processes and diverse signaling pathways in organisms. The detection of the spatiotemporal expression of miRNA in vivo is crucial for uncovering the function of miRNA. However, most of the current detecting techniques cannot reflect the dynamics of miRNA sensitively in vivo. Here, we constructed a miRNA-induced CRISPR-Cas9 platform (MICR) used in marine chordate Ciona. The key component of MICR is a pre-single guide RNA (sgRNA) flanked by miRNA-binding sites that can be released by RNA-induced silencing complex (RISC) cleavage to form functional sgRNA in the presence of complementary miRNA. By using the miRNA-inducible CRISPR-on system (MICR-ON), we successfully detected the dynamic expression of a miRNA csa-miR-4018a during development of Ciona embryo. The detected patterns were validated to be consistent with the results by in situ hybridization. It is worth noting that the expression of csa-miR-4018a was examined by MICR-ON to be present in additional tissues, where no obvious signaling was detected by in situ hybridization, suggesting that the MICR-ON might be a more sensitive approach to detect miRNA signal in living animal. Thus, MICR-ON was demonstrated to be a sensitive and highly efficient approach for monitoring the dynamics of expression of miRNA in vivo and will facilitate the exploration of miRNA functions in biological systems.}, } @article {pmid33875673, year = {2021}, author = {Thongsripong, P and Chandler, JA and Kittayapong, P and Wilcox, BA and Kapan, DD and Bennett, SN}, title = {Metagenomic shotgun sequencing reveals host species as an important driver of virome composition in mosquitoes.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {8448}, pmid = {33875673}, issn = {2045-2322}, support = {P01 AI106695/AI/NIAID NIH HHS/United States ; P20 RR018727/RR/NCRR NIH HHS/United States ; U54 AI065359/AI/NIAID NIH HHS/United States ; }, mesh = {Aedes/*virology ; Animals ; Culex/*virology ; *Genome, Viral ; High-Throughput Nucleotide Sequencing ; Host Specificity ; *Metagenome ; Mosquito Vectors/*virology ; Phylogeny ; RNA Viruses/*physiology ; RNA-Seq ; Thailand ; *Virome ; }, abstract = {High-throughput nucleic acid sequencing has greatly accelerated the discovery of viruses in the environment. Mosquitoes, because of their public health importance, are among those organisms whose viromes are being intensively characterized. Despite the deluge of sequence information, our understanding of the major drivers influencing the ecology of mosquito viromes remains limited. Using methods to increase the relative proportion of microbial RNA coupled with RNA-seq we characterize RNA viruses and other symbionts of three mosquito species collected along a rural to urban habitat gradient in Thailand. The full factorial study design allows us to explicitly investigate the relative importance of host species and habitat in structuring viral communities. We found that the pattern of virus presence was defined primarily by host species rather than by geographic locations or habitats. Our result suggests that insect-associated viruses display relatively narrow host ranges but are capable of spreading through a mosquito population at the geographical scale of our study. We also detected various single-celled and multicellular microorganisms such as bacteria, alveolates, fungi, and nematodes. Our study emphasizes the importance of including ecological information in viromic studies in order to gain further insights into viral ecology in systems where host specificity is driving both viral ecology and evolution.}, } @article {pmid33865960, year = {2021}, author = {Hage, H and Rosso, MN and Tarrago, L}, title = {Distribution of methionine sulfoxide reductases in fungi and conservation of the free-methionine-R-sulfoxide reductase in multicellular eukaryotes.}, journal = {Free radical biology & medicine}, volume = {169}, number = {}, pages = {187-215}, doi = {10.1016/j.freeradbiomed.2021.04.013}, pmid = {33865960}, issn = {1873-4596}, mesh = {*Eukaryota/metabolism ; Fungi/genetics ; Methionine/metabolism ; *Methionine Sulfoxide Reductases/genetics/metabolism ; Oxidation-Reduction ; Phylogeny ; }, abstract = {Methionine, either as a free amino acid or included in proteins, can be oxidized into methionine sulfoxide (MetO), which exists as R and S diastereomers. Almost all characterized organisms possess thiol-oxidoreductases named methionine sulfoxide reductase (Msr) enzymes to reduce MetO back to Met. MsrA and MsrB reduce the S and R diastereomers of MetO, respectively, with strict stereospecificity and are found in almost all organisms. Another type of thiol-oxidoreductase, the free-methionine-R-sulfoxide reductase (fRMsr), identified so far in prokaryotes and a few unicellular eukaryotes, reduces the R MetO diastereomer of the free amino acid. Moreover, some bacteria possess molybdenum-containing enzymes that reduce MetO, either in the free or protein-bound forms. All these Msrs play important roles in the protection of organisms against oxidative stress. Fungi are heterotrophic eukaryotes that colonize all niches on Earth and play fundamental functions, in organic matter recycling, as symbionts, or as pathogens of numerous organisms. However, our knowledge on fungal Msrs is still limited. Here, we performed a survey of msr genes in almost 700 genomes across the fungal kingdom. We show that most fungi possess one gene coding for each type of methionine sulfoxide reductase: MsrA, MsrB, and fRMsr. However, several fungi living in anaerobic environments or as obligate intracellular parasites were devoid of msr genes. Sequence inspection and phylogenetic analyses allowed us to identify non-canonical sequences with potentially novel enzymatic properties. Finaly, we identified several ocurences of msr horizontal gene transfer from bacteria to fungi.}, } @article {pmid33865238, year = {2021}, author = {Xu, X and Smaczniak, C and Muino, JM and Kaufmann, K}, title = {Cell identity specification in plants: lessons from flower development.}, journal = {Journal of experimental botany}, volume = {72}, number = {12}, pages = {4202-4217}, pmid = {33865238}, issn = {1460-2431}, mesh = {Cell Differentiation ; Flowers/metabolism ; Gene Expression Regulation, Developmental ; *Gene Expression Regulation, Plant ; *Plants/genetics/metabolism ; Transcription Factors/genetics/metabolism ; }, abstract = {Multicellular organisms display a fascinating complexity of cellular identities and patterns of diversification. The concept of 'cell type' aims to describe and categorize this complexity. In this review, we discuss the traditional concept of cell types and highlight the impact of single-cell technologies and spatial omics on the understanding of cellular differentiation in plants. We summarize and compare position-based and lineage-based mechanisms of cell identity specification using flower development as a model system. More than understanding ontogenetic origins of differentiated cells, an important question in plant science is to understand their position- and developmental stage-specific heterogeneity. Combinatorial action and crosstalk of external and internal signals is the key to cellular heterogeneity, often converging on transcription factors that orchestrate gene expression programs.}, } @article {pmid33861755, year = {2021}, author = {Menichelli, C and Guitard, V and Martins, RM and Lèbre, S and Lopez-Rubio, JJ and Lecellier, CH and Bréhélin, L}, title = {Identification of long regulatory elements in the genome of Plasmodium falciparum and other eukaryotes.}, journal = {PLoS computational biology}, volume = {17}, number = {4}, pages = {e1008909}, pmid = {33861755}, issn = {1553-7358}, mesh = {Eukaryota/genetics ; Gene Expression Regulation ; Gene Ontology ; Genes, Reporter ; *Genome, Protozoan ; Histones/metabolism ; Plasmodium falciparum/*genetics ; RNA Processing, Post-Transcriptional ; RNA, Antisense/genetics ; RNA, Messenger/genetics ; *Regulatory Sequences, Nucleic Acid ; Transcription, Genetic ; }, abstract = {Long regulatory elements (LREs), such as CpG islands, polydA:dT tracts or AU-rich elements, are thought to play key roles in gene regulation but, as opposed to conventional binding sites of transcription factors, few methods have been proposed to formally and automatically characterize them. We present here a computational approach named DExTER (Domain Exploration To Explain gene Regulation) dedicated to the identification of candidate LREs (cLREs) and apply it to the analysis of the genomes of P. falciparum and other eukaryotes. Our analyses show that all tested genomes contain several cLREs that are somewhat conserved along evolution, and that gene expression can be predicted with surprising accuracy on the basis of these long regions only. Regulation by cLREs exhibits very different behaviours depending on species and conditions. In P. falciparum and other Apicomplexan organisms as well as in Dictyostelium discoideum, the process appears highly dynamic, with different cLREs involved at different phases of the life cycle. For multicellular organisms, the same cLREs are involved in all tissues, but a dynamic behavior is observed along embryonic development stages. In P. falciparum, whose genome is known to be strongly depleted of transcription factors, cLREs are predictive of expression with an accuracy above 70%, and our analyses show that they are associated with both transcriptional and post-transcriptional regulation signals. Moreover, we assessed the biological relevance of one LRE discovered by DExTER in P. falciparum using an in vivo reporter assay. The source code (python) of DExTER is available at https://gite.lirmm.fr/menichelli/DExTER.}, } @article {pmid33850152, year = {2021}, author = {Brosnan, CA and Palmer, AJ and Zuryn, S}, title = {Cell-type-specific profiling of loaded miRNAs from Caenorhabditis elegans reveals spatial and temporal flexibility in Argonaute loading.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {2194}, pmid = {33850152}, issn = {2041-1723}, support = {P40 OD010440/OD/NIH HHS/United States ; }, mesh = {Animals ; Animals, Genetically Modified ; Argonaute Proteins/*genetics/*metabolism ; Caenorhabditis elegans/*genetics ; Caenorhabditis elegans Proteins/genetics/metabolism ; Gene Expression Regulation ; MicroRNAs/*genetics/*metabolism ; Nervous System ; Protein Isoforms ; }, abstract = {Multicellularity has coincided with the evolution of microRNAs (miRNAs), small regulatory RNAs that are integrated into cellular differentiation and homeostatic gene-regulatory networks. However, the regulatory mechanisms underpinning miRNA activity have remained largely obscured because of the precise, and thus difficult to access, cellular contexts under which they operate. To resolve these, we have generated a genome-wide map of active miRNAs in Caenorhabditis elegans by revealing cell-type-specific patterns of miRNAs loaded into Argonaute (AGO) silencing complexes. Epitope-labelled AGO proteins were selectively expressed and immunoprecipitated from three distinct tissue types and associated miRNAs sequenced. In addition to providing information on biological function, we define adaptable miRNA:AGO interactions with single-cell-type and AGO-specific resolution. We demonstrate spatial and temporal dynamicism, flexibility of miRNA loading, and suggest miRNA regulatory mechanisms via AGO selectivity in different tissues and during ageing. Additionally, we resolve widespread changes in AGO-regulated gene expression by analysing translatomes specifically in neurons.}, } @article {pmid33846299, year = {2021}, author = {Shemesh, N and Jubran, J and Dror, S and Simonovsky, E and Basha, O and Argov, C and Hekselman, I and Abu-Qarn, M and Vinogradov, E and Mauer, O and Tiago, T and Carra, S and Ben-Zvi, A and Yeger-Lotem, E}, title = {The landscape of molecular chaperones across human tissues reveals a layered architecture of core and variable chaperones.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {2180}, pmid = {33846299}, issn = {2041-1723}, mesh = {Aging/metabolism ; Animals ; Caenorhabditis elegans/metabolism ; Cell Line ; Conserved Sequence ; Evolution, Molecular ; Gene Expression Regulation ; Humans ; Mice ; Molecular Chaperones/genetics/*metabolism ; Open Reading Frames/genetics ; *Organ Specificity/genetics ; }, abstract = {The sensitivity of the protein-folding environment to chaperone disruption can be highly tissue-specific. Yet, the organization of the chaperone system across physiological human tissues has received little attention. Through computational analyses of large-scale tissue transcriptomes, we unveil that the chaperone system is composed of core elements that are uniformly expressed across tissues, and variable elements that are differentially expressed to fit with tissue-specific requirements. We demonstrate via a proteomic analysis that the muscle-specific signature is functional and conserved. Core chaperones are significantly more abundant across tissues and more important for cell survival than variable chaperones. Together with variable chaperones, they form tissue-specific functional networks. Analysis of human organ development and aging brain transcriptomes reveals that these functional networks are established in development and decline with age. In this work, we expand the known functional organization of de novo versus stress-inducible eukaryotic chaperones into a layered core-variable architecture in multi-cellular organisms.}, } @article {pmid33839924, year = {2021}, author = {Genau, AC and Li, Z and Renzaglia, KS and Fernandez Pozo, N and Nogué, F and Haas, FB and Wilhelmsson, PKI and Ullrich, KK and Schreiber, M and Meyberg, R and Grosche, C and Rensing, SA}, title = {HAG1 and SWI3A/B control of male germ line development in P. patens suggests conservation of epigenetic reproductive control across land plants.}, journal = {Plant reproduction}, volume = {34}, number = {2}, pages = {149-173}, pmid = {33839924}, issn = {2194-7961}, support = {5R25GM107760-07/NH/NIH HHS/United States ; R25 GM107760/GM/NIGMS NIH HHS/United States ; }, mesh = {Biological Evolution ; *Embryophyta ; Epigenesis, Genetic ; *Germ Cells, Plant ; Reproduction/genetics ; }, abstract = {Bryophytes as models to study the male germ line: loss-of-function mutants of epigenetic regulators HAG1 and SWI3a/b demonstrate conserved function in sexual reproduction. With the water-to-land transition, land plants evolved a peculiar haplodiplontic life cycle in which both the haploid gametophyte and the diploid sporophyte are multicellular. The switch between these phases was coined alternation of generations. Several key regulators that control the bauplan of either generation are already known. Analyses of such regulators in flowering plants are difficult due to the highly reduced gametophytic generation, and the fact that loss of function of such genes often is embryo lethal in homozygous plants. Here we set out to determine gene function and conservation via studies in bryophytes. Bryophytes are sister to vascular plants and hence allow evolutionary inferences. Moreover, embryo lethal mutants can be grown and vegetatively propagated due to the dominance of the bryophyte gametophytic generation. We determined candidates by selecting single copy orthologs that are involved in transcriptional control, and of which flowering plant mutants show defects during sexual reproduction, with a focus on the under-studied male germ line. We selected two orthologs, SWI3a/b and HAG1, and analyzed loss-of-function mutants in the moss P. patens. In both mutants, due to lack of fertile spermatozoids, fertilization and hence the switch to the diploid generation do not occur. Pphag1 additionally shows arrested male and impaired female gametangia development. We analyzed HAG1 in the dioecious liverwort M. polymorpha and found that in Mphag1 the development of gametangiophores is impaired. Taken together, we find that involvement of both regulators in sexual reproduction is conserved since the earliest divergence of land plants.}, } @article {pmid33837641, year = {2021}, author = {Abe-Fukasawa, N and Watanabe, R and Gen, Y and Nishino, T and Itasaki, N}, title = {A liquid culture cancer spheroid model reveals low PI3K/Akt pathway activity and low adhesiveness to the extracellular matrix.}, journal = {The FEBS journal}, volume = {288}, number = {19}, pages = {5650-5667}, doi = {10.1111/febs.15867}, pmid = {33837641}, issn = {1742-4658}, mesh = {Animals ; Cell Adhesion/*genetics ; *Cell Culture Techniques ; Cell Line, Tumor ; Cell Polarity/genetics ; Extracellular Matrix/genetics ; Humans ; Mice ; Neoplasm Metastasis ; Neoplasms/*genetics/pathology ; Oncogene Protein v-akt/genetics ; Phosphatidylinositol 3-Kinases/genetics ; Signal Transduction/genetics ; Spheroids, Cellular/metabolism/*pathology ; Transplantation, Heterologous ; }, abstract = {Three-dimensional (3D) cultures of cancer cells in liquid without extracellular matrix (ECM) offer in vitro models for metastasising conditions such as those in vessels and effusion. However, liquid culturing is often hindered by cell adhesiveness, which causes large cell clumps. We previously described a liquid culture material, LA717, which prevents nonclonal cell adhesion and subsequent clumping, thus allowing clonal growth of spheroids in an anchorage-independent manner. Here, we examined such liquid culture cancer spheroids for the acquisition of apical-basal polarity, sensitivity to an Akt inhibitor (anticancer drug MK-2206) and interaction with ECM. The spheroids present apical plasma membrane on the surface, which originated from the failure of polarisation at the single-cell stage and subsequent defects in phosphorylated ezrin accumulation at the cell boundary during the first cleavage, failing internal lumen formation. At the multicellular stage, liquid culture spheroids presented bleb-like protrusion on the surface, which was enhanced by the activation of the PI3K/Akt pathway and reduced by PI3K/Akt inhibitors. Liquid culture spheroids exhibited slow proliferation speed and low endogenous pAkt levels compared with gel-cultured spheroids and 2D-cultured cells, explaining the susceptibility to the Akt-inhibiting anticancer drug. Subcutaneous xenografting and in vitro analysis demonstrated low viability and adhesive property of liquid culture spheroids to ECM, while migratory and invasive capacities were comparable with gel-cultured spheroids. These features agree with the low efficacy of circulating tumour spheroids in the settling step of metastasis. This study demonstrates the feature of anchorage-independent spheroids and validates liquid cultures as a useful method in cancer spheroid research.}, } @article {pmid33834782, year = {2021}, author = {Kwon, HY and Kumar Das, R and Jung, GT and Lee, HG and Lee, SH and Berry, SN and Tan, JKS and Park, S and Yang, JS and Park, S and Baek, K and Park, KM and Lee, JW and Choi, YK and Kim, KH and Kim, S and Kim, KP and Kang, NY and Kim, K and Chang, YT}, title = {Lipid-Oriented Live-Cell Distinction of B and T Lymphocytes.}, journal = {Journal of the American Chemical Society}, volume = {143}, number = {15}, pages = {5836-5844}, doi = {10.1021/jacs.1c00944}, pmid = {33834782}, issn = {1520-5126}, mesh = {Animals ; B-Lymphocytes/chemistry/*cytology/immunology ; Bone Marrow Cells/cytology/metabolism ; Cell Differentiation ; Cell Membrane/chemistry/*metabolism ; Flow Cytometry ; Fluorescent Dyes/*chemistry ; Lipidomics ; Mice ; T-Lymphocytes/chemistry/*cytology/immunology ; }, abstract = {The identification of each cell type is essential for understanding multicellular communities. Antibodies set as biomarkers have been the main toolbox for cell-type recognition, and chemical probes are emerging surrogates. Herein we report the first small-molecule probe, CDgB, to discriminate B lymphocytes from T lymphocytes, which was previously impossible without the help of antibodies. Through the study of the origin of cell specificity, we discovered an unexpected novel mechanism of membrane-oriented live-cell distinction. B cells maintain higher flexibility in their cell membrane than T cells and accumulate the lipid-like probe CDgB more preferably. Because B and T cells share common ancestors, we tracked the cell membrane changes of the progenitor cells and disclosed the dynamic reorganization of the membrane properties over the lymphocyte differentiation progress. This study casts an orthogonal strategy for the small-molecule cell identifier and enriches the toolbox for live-cell distinction from complex cell communities.}, } @article {pmid33802617, year = {2021}, author = {Baluška, F and Miller, WB and Reber, AS}, title = {Biomolecular Basis of Cellular Consciousness via Subcellular Nanobrains.}, journal = {International journal of molecular sciences}, volume = {22}, number = {5}, pages = {}, pmid = {33802617}, issn = {1422-0067}, mesh = {Animals ; Biological Evolution ; Cell Biology ; Cell Membrane/*physiology ; Consciousness/*physiology ; }, abstract = {Cells emerged at the very beginning of life on Earth and, in fact, are coterminous with life. They are enclosed within an excitable plasma membrane, which defines the outside and inside domains via their specific biophysical properties. Unicellular organisms, such as diverse protists and algae, still live a cellular life. However, fungi, plants, and animals evolved a multicellular existence. Recently, we have developed the cellular basis of consciousness (CBC) model, which proposes that all biological awareness, sentience and consciousness are grounded in general cell biology. Here we discuss the biomolecular structures and processes that allow for and maintain this cellular consciousness from an evolutionary perspective.}, } @article {pmid33801615, year = {2021}, author = {Kin, K and Schaap, P}, title = {Evolution of Multicellular Complexity in The Dictyostelid Social Amoebas.}, journal = {Genes}, volume = {12}, number = {4}, pages = {}, pmid = {33801615}, issn = {2073-4425}, support = {100293/Z/12/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Amoeba/*physiology ; Biological Evolution ; Cold Temperature ; Dictyostelium/*physiology ; Evolution, Molecular ; Life Cycle Stages ; Phylogeny ; Signal Transduction ; *Stress, Physiological ; }, abstract = {Multicellularity evolved repeatedly in the history of life, but how it unfolded varies greatly between different lineages. Dictyostelid social amoebas offer a good system to study the evolution of multicellular complexity, with a well-resolved phylogeny and molecular genetic tools being available. We compare the life cycles of the Dictyostelids with closely related amoebozoans to show that complex life cycles were already present in the unicellular common ancestor of Dictyostelids. We propose frost resistance as an early driver of multicellular evolution in Dictyostelids and show that the cell signalling pathways for differentiating spore and stalk cells evolved from that for encystation. The stalk cell differentiation program was further modified, possibly through gene duplication, to evolve a new cell type, cup cells, in Group 4 Dictyostelids. Studies in various multicellular organisms, including Dictyostelids, volvocine algae, and metazoans, suggest as a common principle in the evolution of multicellular complexity that unicellular regulatory programs for adapting to environmental change serve as "proto-cell types" for subsequent evolution of multicellular organisms. Later, new cell types could further evolve by duplicating and diversifying the "proto-cell type" gene regulatory networks.}, } @article {pmid33800339, year = {2021}, author = {Patthy, L}, title = {Exon Shuffling Played a Decisive Role in the Evolution of the Genetic Toolkit for the Multicellular Body Plan of Metazoa.}, journal = {Genes}, volume = {12}, number = {3}, pages = {}, pmid = {33800339}, issn = {2073-4425}, mesh = {Animals ; *Cell Differentiation ; *Evolution, Molecular ; *Exons ; *Models, Genetic ; Transcription Factors/*genetics ; }, abstract = {Division of labor and establishment of the spatial pattern of different cell types of multicellular organisms require cell type-specific transcription factor modules that control cellular phenotypes and proteins that mediate the interactions of cells with other cells. Recent studies indicate that, although constituent protein domains of numerous components of the genetic toolkit of the multicellular body plan of Metazoa were present in the unicellular ancestor of animals, the repertoire of multidomain proteins that are indispensable for the arrangement of distinct body parts in a reproducible manner evolved only in Metazoa. We have shown that the majority of the multidomain proteins involved in cell-cell and cell-matrix interactions of Metazoa have been assembled by exon shuffling, but there is no evidence for a similar role of exon shuffling in the evolution of proteins of metazoan transcription factor modules. A possible explanation for this difference in the intracellular and intercellular toolkits is that evolution of the transcription factor modules preceded the burst of exon shuffling that led to the creation of the proteins controlling spatial patterning in Metazoa. This explanation is in harmony with the temporal-to-spatial transition hypothesis of multicellularity that proposes that cell differentiation may have predated spatial segregation of cell types in animal ancestors.}, } @article {pmid33779495, year = {2022}, author = {Porfírio-Sousa, AL and Tice, AK and Brown, MW and J G Lahr, D}, title = {Phylogenetic reconstruction and evolution of the Rab GTPase gene family in Amoebozoa.}, journal = {Small GTPases}, volume = {13}, number = {1}, pages = {100-113}, pmid = {33779495}, issn = {2154-1256}, mesh = {Phylogeny ; *rab GTP-Binding Proteins/genetics/metabolism ; Evolution, Molecular ; *Amoebozoa/genetics/metabolism ; Eukaryota/metabolism ; }, abstract = {Rab GTPase is a paralog-rich gene family that controls the maintenance of the eukaryotic cell compartmentalization system. Diverse eukaryotes have varying numbers of Rab paralogs. Currently, little is known about the evolutionary pattern of Rab GTPase in most major eukaryotic 'supergroups'. Here, we present a comprehensive phylogenetic reconstruction of the Rab GTPase gene family in the eukaryotic 'supergroup' Amoebozoa, a diverse lineage represented by unicellular and multicellular organisms. We demonstrate that Amoebozoa conserved 20 of the 23 ancestral Rab GTPases predicted to be present in the last eukaryotic common ancestor and massively expanded several 'novel' in-paralogs. Due to these 'novel' in-paralogs, the Rab family composition dramatically varies between the members of Amoebozoa; as a consequence, 'supergroup'-based studies may significantly change our current understanding of the evolution and diversity of this gene family. The high diversity of the Rab GTPase gene family in Amoebozoa makes this 'supergroup' a key lineage to study and advance our knowledge of the evolution of Rab in Eukaryotes.}, } @article {pmid33767367, year = {2021}, author = {Wang, S and Liang, H and Xu, Y and Li, L and Wang, H and Sahu, DN and Petersen, M and Melkonian, M and Sahu, SK and Liu, H}, title = {Genome-wide analyses across Viridiplantae reveal the origin and diversification of small RNA pathway-related genes.}, journal = {Communications biology}, volume = {4}, number = {1}, pages = {412}, pmid = {33767367}, issn = {2399-3642}, mesh = {*Evolution, Molecular ; Genes, Plant ; *Genome, Plant ; Phylogeny ; RNA, Small Untranslated/*genetics ; Viridiplantae/*genetics ; }, abstract = {Small RNAs play a major role in the post-transcriptional regulation of gene expression in eukaryotes. Despite the evolutionary importance of streptophyte algae, knowledge on small RNAs in this group of green algae is almost non-existent. We used genome and transcriptome data of 34 algal and plant species, and performed genome-wide analyses of small RNA (miRNA & siRNA) biosynthetic and degradation pathways. The results suggest that Viridiplantae started to evolve plant-like miRNA biogenesis and degradation after the divergence of the Mesostigmatophyceae in the streptophyte algae. We identified two major evolutionary transitions in small RNA metabolism in streptophyte algae; during the first transition, the origin of DCL-New, DCL1, AGO1/5/10 and AGO4/6/9 in the last common ancestor of Klebsormidiophyceae and all other streptophytes could be linked to abiotic stress responses and evolution of multicellularity in streptophytes. During the second transition, the evolution of DCL 2,3,4, and AGO 2,3,7 as well as DRB1 in the last common ancestor of Zygnematophyceae and embryophytes, suggests their possible contribution to pathogen defense and antibacterial immunity. Overall, the origin and diversification of DICER and AGO along with several other small RNA pathway-related genes among streptophyte algae suggested progressive adaptations of streptophyte algae during evolution to a subaerial environment.}, } @article {pmid33763054, year = {2020}, author = {Roudaire, T and Héloir, MC and Wendehenne, D and Zadoroznyj, A and Dubrez, L and Poinssot, B}, title = {Cross Kingdom Immunity: The Role of Immune Receptors and Downstream Signaling in Animal and Plant Cell Death.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {612452}, pmid = {33763054}, issn = {1664-3224}, mesh = {Animals ; Cell Death/*immunology ; Humans ; Immunity, Innate/immunology ; Inflammasomes/immunology ; Plant Cells/*immunology ; Plant Immunity/*immunology ; Plants/*immunology ; Receptors, Immunologic/*immunology ; Receptors, Pattern Recognition/immunology ; Signal Transduction/*immunology ; }, abstract = {Both plants and animals are endowed with sophisticated innate immune systems to combat microbial attack. In these multicellular eukaryotes, innate immunity implies the presence of cell surface receptors and intracellular receptors able to detect danger signal referred as damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs). Membrane-associated pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs), C-type lectin receptors (CLRs), receptor-like kinases (RLKs), and receptor-like proteins (RLPs) are employed by these organisms for sensing different invasion patterns before triggering antimicrobial defenses that can be associated with a form of regulated cell death. Intracellularly, animals nucleotide-binding and oligomerization domain (NOD)-like receptors or plants nucleotide-binding domain (NBD)-containing leucine rich repeats (NLRs) immune receptors likely detect effectors injected into the host cell by the pathogen to hijack the immune signaling cascade. Interestingly, during the co-evolution between the hosts and their invaders, key cross-kingdom cell death-signaling macromolecular NLR-complexes have been selected, such as the inflammasome in mammals and the recently discovered resistosome in plants. In both cases, a regulated cell death located at the site of infection constitutes a very effective mean for blocking the pathogen spread and protecting the whole organism from invasion. This review aims to describe the immune mechanisms in animals and plants, mainly focusing on cell death signaling pathways, in order to highlight recent advances that could be used on one side or the other to identify the missing signaling elements between the perception of the invasion pattern by immune receptors, the induction of defenses or the transmission of danger signals to other cells. Although knowledge of plant immunity is less advanced, these organisms have certain advantages allowing easier identification of signaling events, regulators and executors of cell death, which could then be exploited directly for crop protection purposes or by analogy for medical research.}, } @article {pmid33760661, year = {2021}, author = {Barnett, AM and Mullaney, JA and Hendriks, C and Le Borgne, L and McNabb, WC and Roy, NC}, title = {Porcine colonoids and enteroids keep the memory of their origin during regeneration.}, journal = {American journal of physiology. Cell physiology}, volume = {320}, number = {5}, pages = {C794-C805}, doi = {10.1152/ajpcell.00420.2020}, pmid = {33760661}, issn = {1522-1563}, mesh = {Animals ; Biomarkers/metabolism ; *Cell Differentiation ; *Cell Lineage ; Cell Proliferation ; Colon/cytology/metabolism/*physiology ; Gene Expression Regulation ; Ileum/cytology/metabolism/*physiology ; Intestinal Mucosa/cytology/metabolism/*physiology ; Male ; Organoids/cytology/metabolism/*physiology ; Phenotype ; Signal Transduction ; Sus scrofa ; Time Factors ; Tissue Culture Techniques ; Transcriptome ; }, abstract = {The development of alternative in vitro culture methods has increased in the last decade as three-dimensional organoids of various tissues, including those of the small and large intestines. Due to their multicellular composition, organoids offer advantages over traditionally used immortalized or primary cell lines. However, organoids must be accurate models of their tissues of origin. This study compared gene expression profiles with respect to markers of specific cell types (stem cells, enterocytes, goblet, and enteroendocrine cells) and barrier maturation (tight junctions) of colonoid and enteroid cultures with their tissues of origin and colonoids with enteroids. Colonoids derived from three healthy pigs formed multilobed structures with a monolayer of cells similar to the crypt structures in colonic tissue. Colonoid and enteroid gene expression signatures were more similar to those found for the tissues of their origin than to each other. However, relative to their derived tissues, organoids had increased gene expression levels of stem cell markers Sox9 and Lgr5 encoding sex-determining region Y-box 9 and leucine-rich repeat-containing G protein-coupled rector 5, respectively. In contrast, expression levels of Occl and Zo1 encoding occludin and zonula occludens 1, respectively, were decreased. Expression levels of the cell lineage markers Atoh1, Cga, and Muc2 encoding atonal homolog 1, chromogranin A, and mucin 2, respectively, were decreased in colonoids, whereas Sglt1 and Apn encoding sodium-glucose transporter 1 and aminopeptidase A, respectively, were decreased in enteroids. These results indicate colonoid and enteroid cultures were predominantly comprised of undifferentiated cell types with decreased barrier maturation relative to their tissues of origin.}, } @article {pmid33748102, year = {2021}, author = {Dhakshinamoorthy, R and Singh, SP}, title = {Evolution of Reproductive Division of Labor - Lessons Learned From the Social Amoeba Dictyostelium discoideum During Its Multicellular Development.}, journal = {Frontiers in cell and developmental biology}, volume = {9}, number = {}, pages = {599525}, pmid = {33748102}, issn = {2296-634X}, abstract = {The origin of multicellular life from unicellular beings is an epochal step in the evolution of eukaryotes. There are several factors influencing cell fate choices during differentiation and morphogenesis of an organism. Genetic make-up of two cells that unite and fertilize is the key factor to signal the formation of various cell-types in due course of development. Although ploidy of the cell-types determines the genetics of an individual, the role of ploidy in cell fate decisions remains unclear. Dictyostelium serves as a versatile model to study the emergence of multicellular life from unicellular life forms. In this work, we investigate the role played by ploidy status of a cell on cell fate commitments during Dictyostelium development. To answer this question, we created Dictyostelium cells of different ploidy: haploid parents and derived isogenic diploids, allowing them to undergo development. The diploid strains used in this study were generated using parasexual genetics. The ploidy status of the haploids and diploids were confirmed by microscopy, flow cytometry, and karyotyping. Prior to reconstitution, we labeled the cells by two methods. First, intragenic expression of red fluorescent protein (RFP) and second, staining the amoebae with a vital, fluorescent dye carboxyfluorescein succinimidyl ester (CFSE). RFP labeled haploid cells allowed us to track the haploids in the chimeric aggregates, slugs, and fruiting bodies. The CFSE labeling method allowed us to track both the haploids and the diploids in the chimeric developmental structures. Our findings illustrate that the haploids demonstrate sturdy cell fate commitment starting from the aggregation stage. The haploids remain crowded at the aggregation centers of the haploid-diploid chimeric aggregates. At the slug stage haploids are predominantly occupying the slug posterior, and are visible in the spore population in the fruiting bodies. Our findings show that cell fate decisions during D. discoideum development are highly influenced by the ploidy status of a cell, adding a new aspect to already known factors Here, we report that ploidy status of a cell could also play a crucial role in regulating the cell fate commitments.}, } @article {pmid33745906, year = {2021}, author = {Johnson, JD and White, NL and Kangabire, A and Abrams, DM}, title = {A dynamical model for the origin of anisogamy.}, journal = {Journal of theoretical biology}, volume = {521}, number = {}, pages = {110669}, doi = {10.1016/j.jtbi.2021.110669}, pmid = {33745906}, issn = {1095-8541}, mesh = {*Biological Evolution ; Computer Simulation ; Female ; Germ Cells ; Humans ; Male ; *Models, Biological ; Reproduction ; }, abstract = {The vast majority of multi-cellular organisms are anisogamous, meaning that male and female sex cells differ in size. It remains an open question how this asymmetric state evolved, presumably from the symmetric isogamous state where all gametes are roughly the same size (drawn from the same distribution). Here, we use tools from the study of nonlinear dynamical systems to develop a simple mathematical model for this phenomenon. Unlike some prior work, we do not assume the existence of mating types. We also model frequency dependent selection via "mean-field coupling," whereby the likelihood that a gamete survives is an increasing function of its size relative to the population's mean gamete size. Using theoretical analysis and numerical simulation, we demonstrate that this mean-referenced competition will almost inevitably result in a stable anisogamous equilibrium, and thus isogamy may naturally lead to anisogamy.}, } @article {pmid33741994, year = {2021}, author = {Redmond, AK and McLysaght, A}, title = {Evidence for sponges as sister to all other animals from partitioned phylogenomics with mixture models and recoding.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {1783}, pmid = {33741994}, issn = {2041-1723}, mesh = {Animals ; Biological Evolution ; Ctenophora/classification/*genetics ; Genome/*genetics ; Genomics/*methods ; Models, Genetic ; *Phylogeny ; Porifera/classification/*genetics ; Species Specificity ; }, abstract = {Resolving the relationships between the major lineages in the animal tree of life is necessary to understand the origin and evolution of key animal traits. Sponges, characterized by their simple body plan, were traditionally considered the sister group of all other animal lineages, implying a gradual increase in animal complexity from unicellularity to complex multicellularity. However, the availability of genomic data has sparked tremendous controversy as some phylogenomic studies support comb jellies taking this position, requiring secondary loss or independent origins of complex traits. Here we show that incorporating site-heterogeneous mixture models and recoding into partitioned phylogenomics alleviates systematic errors that hamper commonly-applied phylogenetic models. Testing on real datasets, we show a great improvement in model-fit that attenuates branching artefacts induced by systematic error. We reanalyse key datasets and show that partitioned phylogenomics does not support comb jellies as sister to other animals at either the supermatrix or partition-specific level.}, } @article {pmid33727612, year = {2021}, author = {Matriano, DM and Alegado, RA and Conaco, C}, title = {Detection of horizontal gene transfer in the genome of the choanoflagellate Salpingoeca rosetta.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {5993}, pmid = {33727612}, issn = {2045-2322}, mesh = {Choanoflagellata/classification/*genetics ; Computational Biology/methods ; Evolution, Molecular ; *Gene Transfer, Horizontal ; *Genome ; Genomics/methods ; Molecular Sequence Annotation ; Phylogeny ; }, abstract = {Horizontal gene transfer (HGT), the movement of heritable materials between distantly related organisms, is crucial in eukaryotic evolution. However, the scale of HGT in choanoflagellates, the closest unicellular relatives of metazoans, and its possible roles in the evolution of animal multicellularity remains unexplored. We identified at least 175 candidate HGTs in the genome of the colonial choanoflagellate Salpingoeca rosetta using sequence-based tests. The majority of these were orthologous to genes in bacterial and microalgal lineages, yet displayed genomic features consistent with the rest of the S. rosetta genome-evidence of ancient acquisition events. Putative functions include enzymes involved in amino acid and carbohydrate metabolism, cell signaling, and the synthesis of extracellular matrix components. Functions of candidate HGTs may have contributed to the ability of choanoflagellates to assimilate novel metabolites, thereby supporting adaptation, survival in diverse ecological niches, and response to external cues that are possibly critical in the evolution of multicellularity in choanoflagellates.}, } @article {pmid33717121, year = {2021}, author = {Ramos-Martínez, E and Hernández-González, L and Ramos-Martínez, I and Pérez-Campos Mayoral, L and López-Cortés, GI and Pérez-Campos, E and Mayoral Andrade, G and Hernández-Huerta, MT and José, MV}, title = {Multiple Origins of Extracellular DNA Traps.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {621311}, pmid = {33717121}, issn = {1664-3224}, mesh = {Animals ; Biological Evolution ; Extracellular Traps/*metabolism ; Humans ; Immunity, Innate ; Neutrophils/*immunology ; Phylogeny ; }, abstract = {Extracellular DNA traps (ETs) are evolutionarily conserved antimicrobial mechanisms present in protozoa, plants, and animals. In this review, we compare their similarities in species of different taxa, and put forward the hypothesis that ETs have multiple origins. Our results are consistent with a process of evolutionary convergence in multicellular organisms through the application of a congruency test. Furthermore, we discuss why multicellularity is related to the presence of a mechanism initiating the formation of ETs.}, } @article {pmid33711511, year = {2021}, author = {Vijg, J}, title = {From DNA damage to mutations: All roads lead to aging.}, journal = {Ageing research reviews}, volume = {68}, number = {}, pages = {101316}, doi = {10.1016/j.arr.2021.101316}, pmid = {33711511}, issn = {1872-9649}, mesh = {Aging/genetics ; Animals ; *DNA Damage ; *DNA Repair/genetics ; Humans ; Mutagenesis ; Mutation ; }, abstract = {Damage to the repository of genetic information in cells has plagued life since its very beginning 3-4 billion years ago. Initially, in the absence of an ozone layer, especially damage from solar UV radiation must have been frequent, with other sources, most notably endogenous sources related to cell metabolism, gaining in importance over time. To cope with this high frequency of damage to the increasingly long DNA molecules that came to encode the growing complexity of cellular functions in cells, DNA repair evolved as one of the earliest genetic traits. Then as now, errors during the repair of DNA damage generated mutations, which provide the substrate for evolution by natural selection. With the emergence of multicellular organisms also the soma became a target of DNA damage and mutations. In somatic cells selection against the adverse effects of DNA damage is greatly diminished, especially in postmitotic cells after the age of first reproduction. Based on an abundance of evidence, DNA damage is now considered as the single most important driver of the degenerative processes that collectively cause aging. Here I will first briefly review the evidence for DNA damage as a cause of aging since the beginning of life. Then, after discussing the possible direct adverse effects of DNA damage and its cellular responses, I will provide an overview of the considerable progress that has recently been made in analyzing a major consequence of DNA damage in humans and other complex organisms: somatic mutations and the resulting genome mosaicism. Recent advances in studying somatic mutagenesis and genome mosaicism in different human and animal tissues will be discussed with a focus on the possible mechanisms through which loss of DNA sequence integrity could cause age-related functional decline and disease.}, } @article {pmid33690952, year = {2021}, author = {Darveau, RP and Curtis, MA}, title = {Oral biofilms revisited: A novel host tissue of bacteriological origin.}, journal = {Periodontology 2000}, volume = {86}, number = {1}, pages = {8-13}, doi = {10.1111/prd.12374}, pmid = {33690952}, issn = {1600-0757}, support = {MR/J011118/1/MRC_/Medical Research Council/United Kingdom ; MR/P012175/2/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Biofilms ; *Dental Plaque ; Gingiva ; Humans ; *Periodontitis ; }, abstract = {The central theme of this volume of Periodontology 2000 is that the microbial dental plaque biofilm, specifically the subgingival dental plaque biofilm, mimics a human tissue in both structure and function. As a basis for this assertion we use the definition of a tissue as an aggregate of similar cells and cell products forming a defined structure with a specific function, in a multicellular organism. Accordingly, we propose that the dental plaque biofilm represents an acquired human tissue largely of bacterial origin that maintains the health of gingival tissue. Furthermore, we acknowledge that disease can be defined as a deviation from the normal structure or an interruption to the function of any body part, organ, or system, and that is manifested by a characteristic set of symptoms and signs whose etiology, pathology, and prognosis may be known or unknown. Therefore, in this volume we present the concept that periodontitis is a disruption of the normal function of the healthy subgingival plaque biofilm with concomitant disruption to its functional properties in relation to innate defense surveillance and tissue maintenance, leading to excessive, deregulated inflammation and tissue destruction.}, } @article {pmid33683515, year = {2021}, author = {Ben-David, Y and Weihs, D}, title = {Modeling force application configurations and morphologies required for cancer cell invasion.}, journal = {Biomechanics and modeling in mechanobiology}, volume = {20}, number = {3}, pages = {1187-1194}, pmid = {33683515}, issn = {1617-7940}, mesh = {Biomechanical Phenomena/physiology ; Computer Simulation ; Elastic Modulus ; Finite Element Analysis ; Humans ; *Models, Biological ; Neoplasm Invasiveness ; Neoplasms/*pathology ; }, abstract = {We show that cell-applied, normal mechanical stresses are required for cells to penetrate into soft substrates, matching experimental observations in invasive cancer cells, while in-plane traction forces alone reproduce observations in non-cancer/noninvasive cells. Mechanobiological interactions of cells with their microenvironment drive migration and cancer invasion. We have previously shown that invasive cancer cells forcefully and rapidly push into impenetrable, physiological stiffness gels and indent them to cell-scale depths (up to 10 μm); normal, noninvasive cells indent at most to 0.7 μm. Significantly indenting cells signpost increased cancer invasiveness and higher metastatic risk in vitro and in vivo, as verified experimentally in different cancer types, yet the underlying cell-applied, force magnitudes and configurations required to produce the cell-scale gel indentations have yet to be evaluated. Hence, we have developed finite element models of forces applied onto soft, impenetrable gels using experimental cell/gel morphologies, gel mechanics, and force magnitudes. We show that in-plane traction forces can only induce small-scale indentations in soft gels (< 0.7 μm), matching experiments with various single, normal cells. Addition of a normal force (on the scale of experimental traction forces) produced cell-scale indentations that matched observations in invasive cancer cells. We note that normal stresses (force and area) determine the indentation depth, while contact area size and morphology have a minor effect, explaining the origin of experimentally observed cell morphologies. We have thus revealed controlling features facilitating invasive indentations by single cancer cells, which will allow application of our model to complex problems, such as multicellular systems.}, } @article {pmid33678014, year = {2021}, author = {Pen, I and Flatt, T}, title = {Asymmetry, division of labour and the evolution of ageing in multicellular organisms.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {376}, number = {1823}, pages = {20190729}, pmid = {33678014}, issn = {1471-2970}, mesh = {*Aging ; Animals ; *Biological Evolution ; *Cell Differentiation ; *Cell Division ; Germ Cells/physiology ; Insecta/*physiology ; Models, Biological ; }, abstract = {Between the 1930s and 1960s, evolutionary geneticists worked out the basic principles of why organisms age. Despite much progress in the evolutionary biology of ageing since that time, however, many puzzles remain. The perhaps most fundamental of these is the question of which organisms should exhibit senescence and which should not (or which should age rapidly and which should not). The evolutionary origin of ageing from a non-senescent state has been conceptually framed, for example, in terms of the separation between germ-line and soma, the distinction between parents and their offspring, and-in unicellular organisms-the unequal distribution of cellular damage at cell division. These ideas seem to be closely related to the concept of 'division of labour' between reproduction and somatic maintenance. Here, we review these concepts and develop a toy model to explore the importance of such asymmetries for the evolution of senescence. We apply our model to the simplest case of a multicellular system: an organism consisting of two totipotent cells. Notably, we find that in organisms which reproduce symmetrically and partition damage equally, senescence is still able to evolve, contrary to previous claims. Our results might have some bearing on understanding the origin of the germ-line-soma separation and the evolution of senescence in multicellular organisms and in colonial species consisting of multiple types of individuals, such as, for example, eusocial insects with their different castes. This article is part of the theme issue 'Ageing and sociality: why, when and how does sociality change ageing patterns?'}, } @article {pmid33677158, year = {2021}, author = {Li, B and Tian, Y and Wen, H and Qi, X and Wang, L and Zhang, J and Li, J and Dong, X and Zhang, K and Li, Y}, title = {Systematic identification and expression analysis of the Sox gene family in spotted sea bass (Lateolabrax maculatus).}, journal = {Comparative biochemistry and physiology. Part D, Genomics & proteomics}, volume = {38}, number = {}, pages = {100817}, doi = {10.1016/j.cbd.2021.100817}, pmid = {33677158}, issn = {1878-0407}, mesh = {Animals ; Bass/*genetics ; Fish Proteins/*genetics ; Multigene Family ; Phylogeny ; SOX Transcription Factors/*genetics ; Transcriptome ; }, abstract = {The Sox gene family encodes a set of transcription factors characterized by a conserved Sry-related high mobility group (HMG)-box domain, which performs a series of essential biological functions in diverse tissues and developmental processes. In this study, the Sox gene family was systematically characterized in spotted sea bass (Lateolabrax maculatus). A total of 26 Sox genes were identified and classified into eight subfamilies, namely, SoxB1, SoxB2, SoxC, SoxD, SoxE, SoxF, SoxH and SoxK. The phylogenetic relationship, exon-intron and domain structure analyses supported their annotation and classification. Comparison of gene copy numbers and chromosome locations among different species indicated that except tandem duplicated paralogs of Sox17/Sox32, duplicated Sox genes in spotted sea bass were generated from teleost-specific whole genome duplication during evolution. In addition, qRT-PCR was performed to detect the expression profiles of Sox genes during development and adulthood. The results showed that the expression of 16 out of 26 Sox genes was induced dramatically at different starting points after the multicellular stage, which is consistent with embryogenesis. At the early stage of sex differentiation, 9 Sox genes exhibited sexually dimorphic expression patterns, among which Sox3, Sox19 and Sox6b showed the most significant ovary-biased expression. Moreover, the distinct expression pattern of Sox genes was observed in different adult tissues. Our results provide a fundamental resource for further investigating the functions of Sox genes in embryonic processes, sex determination and differentiation as well as controlling the homeostasis of adult tissues in spotted sea bass.}, } @article {pmid33675395, year = {2021}, author = {Jong, LW and Fujiwara, T and Hirooka, S and Miyagishima, SY}, title = {Cell size for commitment to cell division and number of successive cell divisions in cyanidialean red algae.}, journal = {Protoplasma}, volume = {258}, number = {5}, pages = {1103-1118}, pmid = {33675395}, issn = {1615-6102}, mesh = {Biological Evolution ; Cell Division ; Cell Size ; *Chlorophyta ; *Rhodophyta ; }, abstract = {Several eukaryotic cell lineages proliferate by multiple fission cell cycles, during which cells grow to manyfold of their original size, then undergo several rounds of cell division without intervening growth. A previous study on volvocine green algae, including both unicellular and multicellular (colonial) species, showed a correlation between the minimum number of successive cell divisions without intervening cellular growth, and the threshold cell size for commitment to the first round of successive cell divisions: two times the average newly born daughter cell volume for unicellular Chlamydomonas reinhardtii, four times for four-celled Tetrabaena socialis, in which each cell in the colony produces a daughter colony by two successive cell divisions, and eight times for the eight-celled Gonium pectorale, in which each cell produces a daughter colony by three successive cell divisions. To assess whether this phenomenon is also applicable to other lineages, we have characterized cyanidialean red algae, namely, Cyanidioschyzon merolae, which proliferates by binary fission, as well as Cyanidium caldarium and Galdieria sulphuraria, which form up to four and 32 daughter cells (autospores), respectively, in a mother cell before hatching out. The result shows that there is also a correlation between the number of successive cell divisions and the threshold cell size for cell division or the first round of the successive cell divisions. In both C. merolae and C. caldarium, the cell size checkpoint for cell division(s) exists in the G1-phase, as previously shown in volvocine green algae. When C. merolae cells were arrested in the G1-phase and abnormally enlarged by conditional depletion of CDKA, the cells underwent two or more successive cell divisions without intervening cellular growth after recovery of CDKA, similarly to C. caldarium and G. sulphuraria. These results suggest that the threshold size for cell division is a major factor in determining the number of successive cell divisions and that evolutionary changes in the mechanism of cell size monitoring resulted in a variation of multiple fission cell cycle in eukaryotic algae.}, } @article {pmid33671243, year = {2021}, author = {Rathor, P and Borza, T and Stone, S and Tonon, T and Yurgel, S and Potin, P and Prithiviraj, B}, title = {A Novel Protein from Ectocarpus sp. Improves Salinity and High Temperature Stress Tolerance in Arabidopsis thaliana.}, journal = {International journal of molecular sciences}, volume = {22}, number = {4}, pages = {}, pmid = {33671243}, issn = {1422-0067}, mesh = {*Adaptation, Physiological/genetics ; Algal Proteins/chemistry/genetics/*metabolism ; Arabidopsis/*genetics/growth & development/*physiology ; Electrolytes/metabolism ; Escherichia coli/metabolism ; Gene Expression Regulation, Plant ; *Hot Temperature ; Phaeophyta/*metabolism ; Phylogeny ; Plants, Genetically Modified ; Promoter Regions, Genetic/genetics ; *Salinity ; Seedlings/genetics ; *Stress, Physiological/genetics ; Tobacco/metabolism ; }, abstract = {Brown alga Ectocarpus sp. belongs to Phaeophyceae, a class of macroalgae that evolved complex multicellularity. Ectocarpus sp. is a dominant seaweed in temperate regions, abundant mostly in the intertidal zones, an environment with high levels of abiotic stresses. Previous transcriptomic analysis of Ectocarpus sp. revealed several genes consistently induced by various abiotic stresses; one of these genes is Esi0017_0056, which encodes a protein with unknown function. Bioinformatics analyses indicated that the protein encoded by Esi0017_0056 is soluble and monomeric. The protein was successfully expressed in Escherichia coli,Arabidopsis thaliana and Nicotiana benthamiana. In A. thaliana the gene was expressed under constitutive and stress inducible promoters which led to improved tolerance to high salinity and temperature stresses. The expression of several key abiotic stress-related genes was studied in transgenic and wild type A. thaliana by qPCR. Expression analysis revealed that genes involved in ABA-induced abiotic stress tolerance, K[+] homeostasis, and chaperon activities were significantly up-regulated in the transgenic line. This study is the first report in which an unknown function Ectocarpus sp. gene, highly responsive to abiotic stresses, was successfully expressed in A. thaliana, leading to improved tolerance to salt and temperature stress.}, } @article {pmid33657376, year = {2021}, author = {Wang, J and Sun, H and Jiang, M and Li, J and Zhang, P and Chen, H and Mei, Y and Fei, L and Lai, S and Han, X and Song, X and Xu, S and Chen, M and Ouyang, H and Zhang, D and Yuan, GC and Guo, G}, title = {Tracing cell-type evolution by cross-species comparison of cell atlases.}, journal = {Cell reports}, volume = {34}, number = {9}, pages = {108803}, doi = {10.1016/j.celrep.2021.108803}, pmid = {33657376}, issn = {2211-1247}, mesh = {Animals ; Caenorhabditis elegans/genetics/metabolism ; Caenorhabditis elegans Proteins/genetics/metabolism ; *Cell Lineage ; Ciona intestinalis/genetics/metabolism ; Databases, Genetic ; *Evolution, Molecular ; *Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Genomics ; Humans ; Mice ; Muscle Cells/classification/*metabolism ; Neurons/classification/*metabolism ; *Single-Cell Analysis ; Species Specificity ; Transcription Factors/*genetics/metabolism ; *Transcriptome ; Zebrafish/genetics/metabolism ; Zebrafish Proteins/genetics/metabolism ; }, abstract = {Cell types are the basic building units of multicellular life, with extensive diversities. The evolution of cell types is a crucial layer of comparative cell biology but is thus far not comprehensively studied. We define a compendium of cell atlases using single-cell RNA-seq (scRNA-seq) data from seven animal species and construct a cross-species cell-type evolutionary hierarchy. We present a roadmap for the origin and diversity of major cell categories and find that muscle and neuron cells are conserved cell types. Furthermore, we identify a cross-species transcription factor (TF) repertoire that specifies major cell categories. Overall, our study reveals conservation and divergence of cell types during animal evolution, which will further expand the landscape of comparative genomics.}, } @article {pmid33656551, year = {2021}, author = {Yang, H and Shi, X and Chen, C and Hou, J and Ji, T and Cheng, J and Birchler, JA}, title = {Predominantly inverse modulation of gene expression in genomically unbalanced disomic haploid maize.}, journal = {The Plant cell}, volume = {33}, number = {4}, pages = {901-916}, pmid = {33656551}, issn = {1532-298X}, mesh = {Chromosomes, Plant ; Dosage Compensation, Genetic ; *Gene Expression Regulation, Plant ; Genes, Plant ; Genome, Plant ; *Haploidy ; Sequence Analysis, RNA ; Zea mays/*genetics ; }, abstract = {The phenotypic consequences of the addition or subtraction of part of a chromosome is more severe than changing the dosage of the whole genome. By crossing diploid trisomies to a haploid inducer, we identified 17 distal segmental haploid disomies that cover ∼80% of the maize genome. Disomic haploids provide a level of genomic imbalance that is not ordinarily achievable in multicellular eukaryotes, allowing the impact to be stronger and more easily studied. Transcriptome size estimates revealed that a few disomies inversely modulate most of the transcriptome. Based on RNA sequencing, the expression levels of genes located on the varied chromosome arms (cis) in disomies ranged from being proportional to chromosomal dosage (dosage effect) to showing dosage compensation with no expression change with dosage. For genes not located on the varied chromosome arm (trans), an obvious trans-acting effect can be observed, with the majority showing a decreased modulation (inverse effect). The extent of dosage compensation of varied cis genes correlates with the extent of trans inverse effects across the 17 genomic regions studied. The results also have implications for the role of stoichiometry in gene expression, the control of quantitative traits, and the evolution of dosage-sensitive genes.}, } @article {pmid33624753, year = {2021}, author = {Junqueira Alves, C and Silva Ladeira, J and Hannah, T and Pedroso Dias, RJ and Zabala Capriles, PV and Yotoko, K and Zou, H and Friedel, RH}, title = {Evolution and Diversity of Semaphorins and Plexins in Choanoflagellates.}, journal = {Genome biology and evolution}, volume = {13}, number = {3}, pages = {}, pmid = {33624753}, issn = {1759-6653}, support = {R01 NS092735/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Axon Guidance ; Biodiversity ; Biological Evolution ; Cell Adhesion Molecules/chemistry/*genetics/metabolism ; Choanoflagellata/classification/*genetics/*metabolism ; Ligands ; Models, Molecular ; Nerve Tissue Proteins/chemistry/*genetics/metabolism ; Phylogeny ; Protein Conformation ; Protein Domains ; Receptors, Cell Surface/genetics ; Semaphorins/*genetics/*metabolism ; }, abstract = {Semaphorins and plexins are cell surface ligand/receptor proteins that affect cytoskeletal dynamics in metazoan cells. Interestingly, they are also present in Choanoflagellata, a class of unicellular heterotrophic flagellates that forms the phylogenetic sister group to Metazoa. Several members of choanoflagellates are capable of forming transient colonies, whereas others reside solitary inside exoskeletons; their molecular diversity is only beginning to emerge. Here, we surveyed genomics data from 22 choanoflagellate species and detected semaphorin/plexin pairs in 16 species. Choanoflagellate semaphorins (Sema-FN1) contain several domain features distinct from metazoan semaphorins, including an N-terminal Reeler domain that may facilitate dimer stabilization, an array of fibronectin type III domains, a variable serine/threonine-rich domain that is a potential site for O-linked glycosylation, and a SEA domain that can undergo autoproteolysis. In contrast, choanoflagellate plexins (Plexin-1) harbor a domain arrangement that is largely identical to metazoan plexins. Both Sema-FN1 and Plexin-1 also contain a short homologous motif near the C-terminus, likely associated with a shared function. Three-dimensional molecular models revealed a highly conserved structural architecture of choanoflagellate Plexin-1 as compared to metazoan plexins, including similar predicted conformational changes in a segment that is involved in the activation of the intracellular Ras-GAP domain. The absence of semaphorins and plexins in several choanoflagellate species did not appear to correlate with unicellular versus colonial lifestyle or ecological factors such as fresh versus salt water environment. Together, our findings support a conserved mechanism of semaphorin/plexin proteins in regulating cytoskeletal dynamics in unicellular and multicellular organisms.}, } @article {pmid33622124, year = {2021}, author = {Evans, SD and Droser, ML and Erwin, DH}, title = {Developmental processes in Ediacara macrofossils.}, journal = {Proceedings. Biological sciences}, volume = {288}, number = {1945}, pages = {20203055}, pmid = {33622124}, issn = {1471-2954}, mesh = {Animals ; *Biological Evolution ; Biota ; *Fossils ; Nervous System ; Phylogeny ; }, abstract = {The Ediacara Biota preserves the oldest fossil evidence of abundant, complex metazoans. Despite their significance, assigning individual taxa to specific phylogenetic groups has proved problematic. To better understand these forms, we identify developmentally controlled characters in representative taxa from the Ediacaran White Sea assemblage and compare them with the regulatory tools underlying similar traits in modern organisms. This analysis demonstrates that the genetic pathways for multicellularity, axial polarity, musculature, and a nervous system were likely present in some of these early animals. Equally meaningful is the absence of evidence for major differentiation of macroscopic body units, including distinct organs, localized sensory machinery or appendages. Together these traits help to better constrain the phylogenetic position of several key Ediacara taxa and inform our views of early metazoan evolution. An apparent lack of heads with concentrated sensory machinery or ventral nerve cords in such taxa supports the hypothesis that these evolved independently in disparate bilaterian clades.}, } @article {pmid33622103, year = {2021}, author = {Ros-Rocher, N and Pérez-Posada, A and Leger, MM and Ruiz-Trillo, I}, title = {The origin of animals: an ancestral reconstruction of the unicellular-to-multicellular transition.}, journal = {Open biology}, volume = {11}, number = {2}, pages = {200359}, pmid = {33622103}, issn = {2046-2441}, mesh = {Alveolata/cytology/genetics ; Animals ; *Evolution, Molecular ; Phylogeny ; }, abstract = {How animals evolved from a single-celled ancestor, transitioning from a unicellular lifestyle to a coordinated multicellular entity, remains a fascinating question. Key events in this transition involved the emergence of processes related to cell adhesion, cell-cell communication and gene regulation. To understand how these capacities evolved, we need to reconstruct the features of both the last common multicellular ancestor of animals and the last unicellular ancestor of animals. In this review, we summarize recent advances in the characterization of these ancestors, inferred by comparative genomic analyses between the earliest branching animals and those radiating later, and between animals and their closest unicellular relatives. We also provide an updated hypothesis regarding the transition to animal multicellularity, which was likely gradual and involved the use of gene regulatory mechanisms in the emergence of early developmental and morphogenetic plans. Finally, we discuss some new avenues of research that will complement these studies in the coming years.}, } @article {pmid33617837, year = {2021}, author = {Debets, VE and Janssen, LMC and Storm, C}, title = {Enhanced persistence and collective migration in cooperatively aligning cell clusters.}, journal = {Biophysical journal}, volume = {120}, number = {8}, pages = {1483-1497}, pmid = {33617837}, issn = {1542-0086}, mesh = {Attention ; Biophysics ; Cell Movement ; Humans ; *Neoplasms ; }, abstract = {Most cells possess the capacity to locomote. Alone or collectively, this allows them to adapt, to rearrange, and to explore their surroundings. The biophysical characterization of such motile processes, in health and in disease, has so far focused mostly on two limiting cases: single-cell motility on the one hand and the dynamics of confluent tissues such as the epithelium on the other. The in-between regime of clusters, composed of relatively few cells moving as a coherent unit, has received less attention. Such small clusters are, however, deeply relevant in development but also in cancer metastasis. In this work, we use cellular Potts models and analytical active matter theory to understand how the motility of small cell clusters changes with N, the number of cells in the cluster. Modeling and theory reveal our two main findings: cluster persistence time increases with N, whereas the intrinsic diffusivity decreases with N. We discuss a number of settings in which the motile properties of more complex clusters can be analytically understood, revealing that the focusing effects of small-scale cooperation and cell-cell alignment can overcome the increased bulkiness and internal disorder of multicellular clusters to enhance overall migrational efficacy. We demonstrate this enhancement for small-cluster collective durotaxis, which is shown to proceed more effectively than for single cells. Our results may provide some novel, to our knowledge, insights into the connection between single-cell and large-scale collective motion and may point the way to the biophysical origins of the enhanced metastatic potential of small tumor cell clusters.}, } @article {pmid33602485, year = {2021}, author = {McKenna, KZ and Wagner, GP and Cooper, KL}, title = {A developmental perspective of homology and evolutionary novelty.}, journal = {Current topics in developmental biology}, volume = {141}, number = {}, pages = {1-38}, doi = {10.1016/bs.ctdb.2020.12.001}, pmid = {33602485}, issn = {1557-8933}, mesh = {Animals ; *Biological Evolution ; Crustacea/anatomy & histology ; Developmental Biology ; *Gene Regulatory Networks ; Genes, Homeobox ; Genitalia, Male/physiology ; Homeodomain Proteins/genetics ; Insecta ; Male ; Pelvis ; Phylogeny ; Transcription Factors/genetics ; Vertebrates/*anatomy & histology ; *Wings, Animal/anatomy & histology ; }, abstract = {The development and evolution of multicellular body plans is complex. Many distinct organs and body parts must be reproduced at each generation, and those that are traceable over long time scales are considered homologous. Among the most pressing and least understood phenomena in evolutionary biology is the mode by which new homologs, or "novelties" are introduced to the body plan and whether the developmental changes associated with such evolution deserve special treatment. In this chapter, we address the concepts of homology and evolutionary novelty through the lens of development. We present a series of case studies, within insects and vertebrates, from which we propose a developmental model of multicellular organ identity. With this model in hand, we make predictions regarding the developmental evolution of body plans and highlight the need for more integrative analysis of developing systems.}, } @article {pmid33600401, year = {2021}, author = {Goldberg, Y and Friedman, J}, title = {Positive interactions within and between populations decrease the likelihood of evolutionary rescue.}, journal = {PLoS computational biology}, volume = {17}, number = {2}, pages = {e1008732}, pmid = {33600401}, issn = {1553-7358}, mesh = {*Adaptation, Physiological ; Animals ; *Biological Evolution ; Computational Biology ; Computer Simulation ; *Ecosystem ; Extinction, Biological ; Humans ; *Models, Biological ; Phenotype ; Probability ; Selection, Genetic ; Stress, Physiological ; *Symbiosis ; }, abstract = {Positive interactions, including intraspecies cooperation and interspecies mutualisms, play crucial roles in shaping the structure and function of many ecosystems, ranging from plant communities to the human microbiome. While the evolutionary forces that form and maintain positive interactions have been investigated extensively, the influence of positive interactions on the ability of species to adapt to new environments is still poorly understood. Here, we use numerical simulations and theoretical analyses to study how positive interactions impact the likelihood that populations survive after an environment deteriorates, such that survival in the new environment requires quick adaptation via the rise of new mutants-a scenario known as evolutionary rescue. We find that the probability of evolutionary rescue in populations engaged in positive interactions is reduced significantly. In cooperating populations, this reduction is largely due to the fact that survival may require at least a minimal number of individuals, meaning that adapted mutants must arise and spread before the population declines below this threshold. In mutualistic populations, the rescue probability is decreased further due to two additional effects-the need for both mutualistic partners to adapt to the new environment, and competition between the two species. Finally, we show that the presence of cheaters reduces the likelihood of evolutionary rescue even further, making it extremely unlikely. These results indicate that while positive interactions may be beneficial in stable environments, they can hinder adaptation to changing environments and thereby elevate the risk of population collapse. Furthermore, these results may hint at the selective pressures that drove co-dependent unicellular species to form more adaptable organisms able to differentiate into multiple phenotypes, including multicellular life.}, } @article {pmid33593190, year = {2021}, author = {He, S and Sieksmeyer, T and Che, Y and Mora, MAE and Stiblik, P and Banasiak, R and Harrison, MC and Šobotník, J and Wang, Z and Johnston, PR and McMahon, DP}, title = {Evidence for reduced immune gene diversity and activity during the evolution of termites.}, journal = {Proceedings. Biological sciences}, volume = {288}, number = {1945}, pages = {20203168}, pmid = {33593190}, issn = {1471-2954}, mesh = {Animals ; Biological Evolution ; *Cockroaches ; *Isoptera/genetics ; Phylogeny ; Social Behavior ; }, abstract = {The evolution of biological complexity is associated with the emergence of bespoke immune systems that maintain and protect organism integrity. Unlike the well-studied immune systems of cells and individuals, little is known about the origins of immunity during the transition to eusociality, a major evolutionary transition comparable to the evolution of multicellular organisms from single-celled ancestors. We aimed to tackle this by characterizing the immune gene repertoire of 18 cockroach and termite species, spanning the spectrum of solitary, subsocial and eusocial lifestyles. We find that key transitions in termite sociality are correlated with immune gene family contractions. In cross-species comparisons of immune gene expression, we find evidence for a caste-specific social defence system in termites, which appears to operate at the expense of individual immune protection. Our study indicates that a major transition in organismal complexity may have entailed a fundamental reshaping of the immune system optimized for group over individual defence.}, } @article {pmid33588307, year = {2021}, author = {Crawford, MA and Schmidt, WF and Broadhurst, CL and Wang, Y}, title = {Lipids in the origin of intracellular detail and speciation in the Cambrian epoch and the significance of the last double bond of docosahexaenoic acid in cell signaling.}, journal = {Prostaglandins, leukotrienes, and essential fatty acids}, volume = {166}, number = {}, pages = {102230}, doi = {10.1016/j.plefa.2020.102230}, pmid = {33588307}, issn = {1532-2823}, mesh = {Animals ; Brain/metabolism ; Carbon/metabolism ; Cell Membrane/metabolism ; Docosahexaenoic Acids/chemistry/*history/*metabolism ; *Electrons ; Fatty Acids, Unsaturated/chemistry/*history/*metabolism ; History, Ancient ; Humans ; Hydrogen/metabolism ; Intracellular Space/*metabolism ; Neurons/metabolism ; Retina/metabolism ; *Signal Transduction ; }, abstract = {One of the great unanswered biological questions is the absolute necessity of the polyunsaturated lipid docosahexaenoic acid (DHA; 22:6n-3) in retinal and neural tissues. Everything from the simple eye spot of dinoflagellates to cephalopods to every class of vertebrates uses DHA, yet it is abundant only in cold water marine food chains. Docosapentaenoic acids (DPAs; 22:5n-6 and especially 22:5n-3) are fairly plentiful in food chains yet cannot substitute for DHA. About 600 million years ago, multi-cellular, air breathing systems evolved rapidly and 32 phyla came into existence in a short geological time span; the "Cambrian Explosion". Eukaryotic intracellular detail requires cell membranes, which are constructed of complex lipids, and proteins. Proteins and nucleic acids would have been abundant during the first 2.5-5 billion years of anaerobic life but lipids, especially unsaturated fatty acids, would not. We hypothesize lipid biology was a key driver of the Cambrian Explosion, because it alone provides for compartmentalization and specialization within cells DHA has six methylene interrupted double bonds providing controlled electron flow at precise energy levels; this is essential for visual acuity and truthful execution of the neural pathways which make up our recollections, information processing and consciousness. The last double bond is critical for the evolution and function of the photoreceptor and neuronal and synaptic signaling systems. It completes a quantum mechanical device for the regulation of current flow with absolute signal precision based on electron tunneling (ET). DHA's methylene interruption distance is < 6 Å, making ET transfer between the π-orbitals feasible throughout the molecule. The possibility fails if one double bond is removed and replaced by a saturated bond as in the DPAs. The molecular biophysical foundation of neural signaling can also include the discrete pattern of paired spin states that arise in the DHA double bond and methylene regions. The complexity depends upon the number of C13 and H1 molecular sites in which spin states are coupled. Electron wave harmonics with entanglement and cohesion provide a mechanism for learning and memory, and power cognition and complex human brain functions.}, } @article {pmid33575354, year = {2021}, author = {Pourhasanzade, F and Sabzpoushan, SH}, title = {A New Mathematical Model for Controlling Tumor Growth Based on Microenvironment Acidity and Oxygen Concentration.}, journal = {BioMed research international}, volume = {2021}, number = {}, pages = {8886050}, pmid = {33575354}, issn = {2314-6141}, mesh = {Animals ; Humans ; Male ; Mice ; Mice, Nude ; Neoplasms/*metabolism ; Oxygen/*metabolism ; *Tumor Microenvironment/drug effects/physiology ; }, abstract = {Hypoxia and the pH level of the tumor microenvironment have a great impact on the treatment of tumors. Here, the tumor growth is controlled by regulating the oxygen concentration and the acidity of the tumor microenvironment by introducing a two-dimensional multiscale cellular automata model of avascular tumor growth. The spatiotemporal evolution of tumor growth and metabolic variations is modeled based on biological assumptions, physical structure, states of cells, and transition rules. Each cell is allocated to one of the following states: proliferating cancer, nonproliferating cancer, necrotic, and normal cells. According to the response of the microenvironmental conditions, each cell consumes/produces metabolic factors and updates its state based on some stochastic rules. The input parameters are compatible with cancer biology using experimental data. The effect of neighborhoods during mitosis and simulating spatial heterogeneity is studied by considering multicellular layer structure of tumor. A simple Darwinist mutation is considered by introducing a critical parameter (Nmm) that affects division probability of the proliferative tumor cells based on the microenvironmental conditions and cancer hallmarks. The results show that Nmm regulation has a significant influence on the dynamics of tumor growth, the growth fraction, necrotic fraction, and the concentration levels of the metabolic factors. The model not only is able to simulate the in vivo tumor growth quantitatively and qualitatively but also can simulate the concentration of metabolic factors, oxygen, and acidity graphically. The results show the spatial heterogeneity effects on the proliferation of cancer cells and the rest of the system. By increasing Nmm, tumor shrinkage and significant increasing in the oxygen concentration and the pH value of the tumor microenvironment are observed. The results demonstrate the model's ability, providing an essential tool for simulating different tumor evolution scenarios of a patient and reliable prediction of spatiotemporal progression of tumors for utilizing in personalized therapy.}, } @article {pmid33565083, year = {2021}, author = {Bustamante, DE and Yeon Won, B and Wynne, MJ and Cho, TO}, title = {Molecular and morphological analyses reveal new taxa additions to the tribe Streblocladieae (Rhodomelaceae, Rhodophyta).}, journal = {Journal of phycology}, volume = {57}, number = {3}, pages = {817-830}, doi = {10.1111/jpy.13144}, pmid = {33565083}, issn = {1529-8817}, mesh = {Evolution, Molecular ; Phylogeny ; *Rhodophyta ; }, abstract = {The recent segregation of 12 genera in the tribe Streblocladieae suggests that the taxonomy of some species belonging to Polysiphonia sensu lato is updated with the transfer and the proposal of new combinations. Accordingly, six new additions to the tribe Streblocladieae on the basis of morphological and molecular analyses are presented as a consequence of this new segregation. These additions include the description of the new species Carradoriella platensis sp. nov., the proposal of the following new combinations Eutrichosiphonia paniculata comb. nov., E. tapinocarpa comb. nov., and the reinstatement of Vertebrata curta, V. decipiens, and V. patersonis. Additionally, our morphological observations identified additional diagnostic features for two genera of the Streblocladieae. Carradoriella has branches with sexual reproductive structures arranged adaxially on branchlets, and the recently described Eutrichosiphonia has rhizoids with multicellular digitate haptera. Our study gives insights in regards to the distribution, the diagnostic features for delimiting genera morphologically, and the molecular evolutionary relationships in the Streblocladieae.}, } @article {pmid33561386, year = {2021}, author = {Prostak, SM and Robinson, KA and Titus, MA and Fritz-Laylin, LK}, title = {The actin networks of chytrid fungi reveal evolutionary loss of cytoskeletal complexity in the fungal kingdom.}, journal = {Current biology : CB}, volume = {31}, number = {6}, pages = {1192-1205.e6}, pmid = {33561386}, issn = {1879-0445}, support = {R01 GM122917/GM/NIGMS NIH HHS/United States ; }, mesh = {Actin Cytoskeleton/*metabolism ; Actins/*metabolism ; Amphibians/microbiology ; Animals ; Chytridiomycota/*classification/*metabolism ; *Evolution, Molecular ; }, abstract = {Cells from across the eukaryotic tree use actin polymer networks for a wide variety of functions, including endocytosis, cytokinesis, and cell migration. Despite this functional conservation, the actin cytoskeleton has undergone significant diversification, highlighted by the differences in the actin networks of mammalian cells and yeast. Chytrid fungi diverged before the emergence of the Dikarya (multicellular fungi and yeast) and therefore provide a unique opportunity to study actin cytoskeletal evolution. Chytrids have two life stages: zoospore cells that can swim with a flagellum and sessile sporangial cells that, like multicellular fungi, are encased in a chitinous cell wall. Here, we show that zoospores of the amphibian-killing chytrid Batrachochytrium dendrobatidis (Bd) build dynamic actin structures resembling those of animal cells, including an actin cortex, pseudopods, and filopodia-like spikes. In contrast, Bd sporangia assemble perinuclear actin shells and actin patches similar to those of yeast. The use of specific small-molecule inhibitors indicate that nearly all of Bd's actin structures are dynamic and use distinct nucleators: although pseudopods and actin patches are Arp2/3 dependent, the actin cortex appears formin dependent and actin spikes require both nucleators. Our analysis of multiple chytrid genomes reveals actin regulators and myosin motors found in animals, but not dikaryotic fungi, as well as fungal-specific components. The presence of animal- and yeast-like actin cytoskeletal components in the genome combined with the intermediate actin phenotypes in Bd suggests that the simplicity of the yeast cytoskeleton may be due to evolutionary loss.}, } @article {pmid33550955, year = {2021}, author = {Ginsburg, S and Jablonka, E}, title = {Evolutionary transitions in learning and cognition.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {376}, number = {1821}, pages = {20190766}, pmid = {33550955}, issn = {1471-2970}, mesh = {Animals ; *Biological Evolution ; Cognition/*physiology ; Learning/*physiology ; Phylogeny ; }, abstract = {We define a cognitive system as a system that can learn, and adopt an evolutionary-transition-oriented framework for analysing different types of neural cognition. This enables us to classify types of cognition and point to the continuities and discontinuities among them. The framework we use for studying evolutionary transitions in learning capacities focuses on qualitative changes in the integration, storage and use of neurally processed information. Although there are always grey areas around evolutionary transitions, we recognize five major neural transitions, the first two of which involve animals at the base of the phylogenetic tree: (i) the evolutionary transition from learning in non-neural animals to learning in the first neural animals; (ii) the transition to animals showing limited, elemental associative learning, entailing neural centralization and primary brain differentiation; (iii) the transition to animals capable of unlimited associative learning, which, on our account, constitutes sentience and entails hierarchical brain organization and dedicated memory and value networks; (iv) the transition to imaginative animals that can plan and learn through selection among virtual events; and (v) the transition to human symbol-based cognition and cultural learning. The focus on learning provides a unifying framework for experimental and theoretical studies of cognition in the living world. This article is part of the theme issue 'Basal cognition: multicellularity, neurons and the cognitive lens'.}, } @article {pmid33550954, year = {2021}, author = {Jékely, G and Godfrey-Smith, P and Keijzer, F}, title = {Reafference and the origin of the self in early nervous system evolution.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {376}, number = {1821}, pages = {20190764}, pmid = {33550954}, issn = {1471-2970}, mesh = {Animals ; Cnidaria/physiology ; Ctenophora/physiology ; Efferent Pathways/*physiology ; Nervous System/chemistry ; *Nervous System Physiological Phenomena ; Placozoa/physiology ; Porifera/physiology ; *Proprioception ; }, abstract = {Discussions of the function of early nervous systems usually focus on a causal flow from sensors to effectors, by which an animal coordinates its actions with exogenous changes in its environment. We propose, instead, that much early sensing was reafferent; it was responsive to the consequences of the animal's own actions. We distinguish two general categories of reafference-translocational and deformational-and use these to survey the distribution of several often-neglected forms of sensing, including gravity sensing, flow sensing and proprioception. We discuss sensing of these kinds in sponges, ctenophores, placozoans, cnidarians and bilaterians. Reafference is ubiquitous, as ongoing action, especially whole-body motility, will almost inevitably influence the senses. Corollary discharge-a pathway or circuit by which an animal tracks its own actions and their reafferent consequences-is not a necessary feature of reafferent sensing but a later-evolving mechanism. We also argue for the importance of reafferent sensing to the evolution of the body-self, a form of organization that enables an animal to sense and act as a single unit. This article is part of the theme issue 'Basal cognition: multicellularity, neurons and the cognitive lens'.}, } @article {pmid33550952, year = {2021}, author = {Pezzulo, G and LaPalme, J and Durant, F and Levin, M}, title = {Bistability of somatic pattern memories: stochastic outcomes in bioelectric circuits underlying regeneration.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {376}, number = {1821}, pages = {20190765}, pmid = {33550952}, issn = {1471-2970}, mesh = {Animals ; *Cell Communication ; *Cognition ; Cognitive Science ; Electrophysiological Phenomena/physiology ; Models, Neurological ; Planarians/*physiology ; *Regeneration ; }, abstract = {Nervous systems' computational abilities are an evolutionary innovation, specializing and speed-optimizing ancient biophysical dynamics. Bioelectric signalling originated in cells' communication with the outside world and with each other, enabling cooperation towards adaptive construction and repair of multicellular bodies. Here, we review the emerging field of developmental bioelectricity, which links the field of basal cognition to state-of-the-art questions in regenerative medicine, synthetic bioengineering and even artificial intelligence. One of the predictions of this view is that regeneration and regulative development can restore correct large-scale anatomies from diverse starting states because, like the brain, they exploit bioelectric encoding of distributed goal states-in this case, pattern memories. We propose a new interpretation of recent stochastic regenerative phenotypes in planaria, by appealing to computational models of memory representation and processing in the brain. Moreover, we discuss novel findings showing that bioelectric changes induced in planaria can be stored in tissue for over a week, thus revealing that somatic bioelectric circuits in vivo can implement a long-term, re-writable memory medium. A consideration of the mechanisms, evolution and functionality of basal cognition makes novel predictions and provides an integrative perspective on the evolution, physiology and biomedicine of information processing in vivo. This article is part of the theme issue 'Basal cognition: multicellularity, neurons and the cognitive lens'.}, } @article {pmid33550951, year = {2021}, author = {Göhde, R and Naumann, B and Laundon, D and Imig, C and McDonald, K and Cooper, BH and Varoqueaux, F and Fasshauer, D and Burkhardt, P}, title = {Choanoflagellates and the ancestry of neurosecretory vesicles.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {376}, number = {1821}, pages = {20190759}, pmid = {33550951}, issn = {1471-2970}, mesh = {*Biological Evolution ; Choanoflagellata/*physiology ; R-SNARE Proteins/*metabolism ; Synaptic Vesicles/*physiology ; }, abstract = {Neurosecretory vesicles are highly specialized trafficking organelles that store neurotransmitters that are released at presynaptic nerve endings and are, therefore, important for animal cell-cell signalling. Despite considerable anatomical and functional diversity of neurons in animals, the protein composition of neurosecretory vesicles in bilaterians appears to be similar. This similarity points towards a common evolutionary origin. Moreover, many putative homologues of key neurosecretory vesicle proteins predate the origin of the first neurons, and some even the origin of the first animals. However, little is known about the molecular toolkit of these vesicles in non-bilaterian animals and their closest unicellular relatives, making inferences about the evolutionary origin of neurosecretory vesicles extremely difficult. By comparing 28 proteins of the core neurosecretory vesicle proteome in 13 different species, we demonstrate that most of the proteins are present in unicellular organisms. Surprisingly, we find that the vesicular membrane-associated soluble N-ethylmaleimide-sensitive factor attachment protein receptor protein synaptobrevin is localized to the vesicle-rich apical and basal pole in the choanoflagellate Salpingoeca rosetta. Our 3D vesicle reconstructions reveal that the choanoflagellates S. rosetta and Monosiga brevicollis exhibit a polarized and diverse vesicular landscape reminiscent of the polarized organization of chemical synapses that secrete the content of neurosecretory vesicles into the synaptic cleft. This study sheds light on the ancestral molecular machinery of neurosecretory vesicles and provides a framework to understand the origin and evolution of secretory cells, synapses and neurons. This article is part of the theme issue 'Basal cognition: multicellularity, neurons and the cognitive lens'.}, } @article {pmid33550950, year = {2021}, author = {Levin, M and Keijzer, F and Lyon, P and Arendt, D}, title = {Uncovering cognitive similarities and differences, conservation and innovation.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {376}, number = {1821}, pages = {20200458}, pmid = {33550950}, issn = {1471-2970}, mesh = {Animals ; *Biological Evolution ; Cognition/*physiology ; *Nervous System Physiological Phenomena ; }, abstract = {This article is part of the theme issue 'Basal cognition: multicellularity, neurons and the cognitive lens'.}, } @article {pmid33550949, year = {2021}, author = {Moroz, LL and Romanova, DY and Kohn, AB}, title = {Neural versus alternative integrative systems: molecular insights into origins of neurotransmitters.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {376}, number = {1821}, pages = {20190762}, pmid = {33550949}, issn = {1471-2970}, support = {R01 NS114491/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Cell Communication/*physiology ; *Evolution, Molecular ; Neurotransmitter Agents/*chemistry ; Placozoa/physiology ; *Signal Transduction ; }, abstract = {Transmitter signalling is the universal chemical language of any nervous system, but little is known about its early evolution. Here, we summarize data about the distribution and functions of neurotransmitter systems in basal metazoans as well as outline hypotheses of their origins. We explore the scenario that neurons arose from genetically different populations of secretory cells capable of volume chemical transmission and integration of behaviours without canonical synapses. The closest representation of this primordial organization is currently found in Placozoa, disk-like animals with the simplest known cell composition but complex behaviours. We propose that injury-related signalling was the evolutionary predecessor for integrative functions of early transmitters such as nitric oxide, ATP, protons, glutamate and small peptides. By contrast, acetylcholine, dopamine, noradrenaline, octopamine, serotonin and histamine were recruited as canonical neurotransmitters relatively later in animal evolution, only in bilaterians. Ligand-gated ion channels often preceded the establishment of novel neurotransmitter systems. Moreover, lineage-specific diversification of neurotransmitter receptors occurred in parallel within Cnidaria and several bilaterian lineages, including acoels. In summary, ancestral diversification of secretory signal molecules provides unique chemical microenvironments for behaviour-driven innovations that pave the way to complex brain functions and elementary cognition. This article is part of the theme issue 'Basal cognition: multicellularity, neurons and the cognitive lens'.}, } @article {pmid33550948, year = {2021}, author = {Arendt, D}, title = {Elementary nervous systems.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {376}, number = {1821}, pages = {20200347}, pmid = {33550948}, issn = {1471-2970}, mesh = {Animals ; Behavior, Animal/*physiology ; *Biological Evolution ; *Body Size ; Cilia/*physiology ; Nerve Net/*physiology ; }, abstract = {The evolutionary origin of the nervous system has been a matter of long-standing debate. This is due to the different perspectives taken. Earlier studies addressed nervous system origins at the cellular level. They focused on the selective advantage of the first neuron in its local context, and considered vertical sensory-motor reflex arcs the first nervous system. Later studies emphasized the value of the nervous system at the tissue level. Rather than acting locally, early neurons were seen as part of an elementary nerve net that enabled the horizontal coordination of tissue movements. Opinions have also differed on the nature of effector cells. While most authors have favoured contractile systems, others see the key output of the incipient nervous system in the coordination of motile cilia, or the secretion of antimicrobial peptides. I will discuss these divergent views and explore how they can be validated by molecular and single-cell data. From this survey, possible consensus emerges: (i) the first manifestation of the nervous system likely was a nerve net, whereas specialized local circuits evolved later; (ii) different nerve nets may have evolved for the coordination of contractile or cilia-driven movements; (iii) all evolving nerve nets facilitated new forms of animal behaviour with increasing body size. This article is part of the theme issue 'Basal cognition: multicellularity, neurons and the cognitive lens'.}, } @article {pmid33542245, year = {2021}, author = {Grum-Grzhimaylo, AA and Bastiaans, E and van den Heuvel, J and Berenguer Millanes, C and Debets, AJM and Aanen, DK}, title = {Somatic deficiency causes reproductive parasitism in a fungus.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {783}, pmid = {33542245}, issn = {2041-1723}, mesh = {Cell Fusion ; DNA Mutational Analysis ; *Evolution, Molecular ; Fungal Proteins/*genetics/metabolism ; Gene Knockout Techniques ; Genes, Fungal/genetics ; Hyphae/*physiology ; Mutation ; Neurospora crassa/*physiology ; }, abstract = {Some multicellular organisms can fuse because mergers potentially provide mutual benefits. However, experimental evolution in the fungus Neurospora crassa has demonstrated that free fusion of mycelia favours cheater lineages, but the mechanism and evolutionary dynamics of this exploitation are unknown. Here we show, paradoxically, that all convergently evolved cheater lineages have similar fusion deficiencies. These mutants are unable to initiate fusion but retain access to wild-type mycelia that fuse with them. This asymmetry reduces cheater-mutant contributions to somatic substrate-bound hyphal networks, but increases representation of their nuclei in the aerial reproductive hyphae. Cheaters only benefit when relatively rare and likely impose genetic load reminiscent of germline senescence. We show that the consequences of somatic fusion can be unequally distributed among fusion partners, with the passive non-fusing partner profiting more. We discuss how our findings may relate to the extensive variation in fusion frequency of fungi found in nature.}, } @article {pmid33539025, year = {2021}, author = {Gostner, JM and Fuchs, D and Kurz, K}, title = {Metabolic Stress and Immunity: Nutrient-Sensing Kinases and Tryptophan Metabolism.}, journal = {Advances in experimental medicine and biology}, volume = {1275}, number = {}, pages = {395-405}, pmid = {33539025}, issn = {0065-2598}, mesh = {Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics ; Kynurenine ; Nutrients ; *Protein Serine-Threonine Kinases ; Stress, Physiological ; *Tryptophan ; }, abstract = {The tryptophan catabolizing enzyme indoleamine 2,3-dioxygenase (IDO-1) has gained major attention due the immunoregulatory nature of this pathway. Both depletion of tryptophan concentrations as well as the accumulation of downstream metabolites are relevant for the mediation of the manifold consequences of increased tryptophan metabolism. Increased tryptophan catabolism is indicative for several chronic inflammatory disorders such as infections, autoimmune diseases or cancer. Low tryptophan availability is likely to be involved in the manifestation of a variety of comorbidities such as anemia, cachexia, depression and neurocognitive disturbances.Several nutrient sensing kinases are implicated in the downstream effects of dysregulated tryptophan metabolism. These include mechanisms that were conserved during evolution but have gained special features in multicellular eukaryotes, such as pathways regulated by eukaryotic translation initiation factor 2 (eIF-2)-alpha kinase (GCN2, also named general control nonderepressible 2 kinase), 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK) and target of rapamycin (TOR).The interplay between IDO-1 and above-mentioned pathway seems to be highly context dependent. A better understanding of the crosstalk is necessary to support the search for druggable targets for the treatment of inflammatory and autoimmune disorders.}, } @article {pmid33535413, year = {2021}, author = {Parker, GA}, title = {How Soon Hath Time… A History of Two "Seminal" Publications.}, journal = {Cells}, volume = {10}, number = {2}, pages = {}, pmid = {33535413}, issn = {2073-4409}, mesh = {Animals ; Female ; Insecta ; Male ; Sexual Selection/*physiology ; }, abstract = {This review documents the history of the two papers written half a century ago that relate to this special issue of Cells. The first, "Sperm competition and its evolutionary consequences in the insects" (Biological Reviews, 1970), stressed that sexual selection continues after ejaculation, resulting in many adaptations (e.g., postcopulatory guarding phases, copulatory plugs, seminal fluid components that modify female reproduction, and optimal ejaculation strategies), an aspect not considered by Darwin in his classic treatise of 1871. Sperm competition has subsequently been studied in many taxa, and post-copulatory sexual selection is now considered an important sequel to Darwinian pre-copulatory sexual selection. The second, "The origin and evolution of gamete dimorphism and the male-female phenomenon" (Journal of Theoretical Biology, 1972) showed how selection, based on gamete competition between individuals, can give rise to anisogamy in an isogamous broadcast spawning ancestor. This theory, which has subsequently been developed in various ways, is argued to form the most powerful explanation of why there are two sexes in most multicellular organisms. Together, the two papers have influenced our general understanding of the evolutionary differentiation of the two forms of gametic cells, and the divergence of sexual strategies between males and females under sexual selection.}, } @article {pmid33529558, year = {2021}, author = {Berger, D and Stångberg, J and Baur, J and Walters, RJ}, title = {Elevated temperature increases genome-wide selection on de novo mutations.}, journal = {Proceedings. Biological sciences}, volume = {288}, number = {1944}, pages = {20203094}, pmid = {33529558}, issn = {1471-2954}, mesh = {*Adaptation, Physiological ; Animals ; *Climate Change ; Coleoptera/*genetics ; DNA Mutational Analysis ; Mutation ; *Selection, Genetic ; *Temperature ; }, abstract = {Adaptation in new environments depends on the amount of genetic variation available for evolution, and the efficacy by which natural selection discriminates among this variation. However, whether some ecological factors reveal more genetic variation, or impose stronger selection pressures than others, is typically not known. Here, we apply the enzyme kinetic theory to show that rising global temperatures are predicted to intensify natural selection throughout the genome by increasing the effects of DNA sequence variation on protein stability. We test this prediction by (i) estimating temperature-dependent fitness effects of induced mutations in seed beetles adapted to ancestral or elevated temperature, and (ii) calculate 100 paired selection estimates on mutations in benign versus stressful environments from unicellular and multicellular organisms. Environmental stress per se did not increase mean selection on de novo mutation, suggesting that the cost of adaptation does not generally increase in new ecological settings to which the organism is maladapted. However, elevated temperature increased the mean strength of selection on genome-wide polymorphism, signified by increases in both mutation load and mutational variance in fitness. These results have important implications for genetic diversity gradients and the rate and repeatability of evolution under climate change.}, } @article {pmid33520185, year = {2021}, author = {Naimark, E and Kirpotin, D and Boeva, N and Gmoshinskiy, V and Kalinina, M and Lyupina, Y and Markov, A and Nikitin, M and Shokurov, A and Volkov, D}, title = {Taphonomic experiments imply a possible link between the evolution of multicellularity and the fossilization potential of soft-bodied organisms.}, journal = {Ecology and evolution}, volume = {11}, number = {2}, pages = {1037-1056}, pmid = {33520185}, issn = {2045-7758}, abstract = {The reliability of evolutionary reconstructions based on the fossil record critically depends on our knowledge of the factors affecting the fossilization of soft-bodied organisms. Despite considerable research effort, these factors are still poorly understood. In order to elucidate the main prerequisites for the preservation of soft-bodied organisms, we conducted long-term (1-5 years) taphonomic experiments with the model crustacean Artemia salina buried in five different sediments. The subsequent analysis of the carcasses and sediments revealed that, in our experimental settings, better preservation was associated with the fast deposition of aluminum and silicon on organic tissues. Other elements such as calcium, magnesium, and iron, which can also accumulate quickly on the carcasses, appear to be much less efficient in preventing decay. Next, we asked if the carcasses of uni- and multicellular organisms differ in their ability to accumulate aluminum ions on their surface. The experiments with the flagellate Euglena gracilis and the sponge Spongilla lacustris showed that aluminum ions are more readily deposited onto a multicellular body. This was further confirmed by the experiments with uni- and multicellular stages of the social ameba Dictyostelium discoideum. The results lead us to speculate that the evolution of cell adhesion molecules, which provide efficient cell-cell and cell-substrate binding, probably can explain the rich fossil record of soft-bodied animals, the comparatively poor fossil record of nonskeletal unicellular eukaryotes, and the explosive emergence of the Cambrian diversity of soft-bodied fossils.}, } @article {pmid33507545, year = {2021}, author = {Li, J and Meng, Q and Fu, Y and Yu, X and Ji, T and Chao, Y and Chen, Q and Li, Y and Bian, H}, title = {Novel insights: Dynamic foam cells derived from the macrophage in atherosclerosis.}, journal = {Journal of cellular physiology}, volume = {236}, number = {9}, pages = {6154-6167}, doi = {10.1002/jcp.30300}, pmid = {33507545}, issn = {1097-4652}, mesh = {Animals ; Atherosclerosis/*pathology ; Cell Communication ; Cholesterol/metabolism ; Esterification ; Foam Cells/metabolism/*pathology ; Humans ; Metabolome ; }, abstract = {Atherosclerosis can be regarded as a chronic disease derived from the interaction between disordered lipoproteins and an unsuitable immune response. The evolution of foam cells is not only a significant pathological change in the early stage of atherosclerosis but also a key stage in the occurrence and development of atherosclerosis. The formation of foam cells is mainly caused by the imbalance among lipids uptake, lipids treatment, and reverse cholesterol transport. Although a large number of studies have summarized the source of foam cells and the mechanism of foam cells formation, we propose a new idea about foam cells in atherosclerosis. Rather than an isolated microenvironment, the macrophage multiple lipid uptake pathways, lipid internalization, lysosome, mitochondria, endoplasmic reticulum, neutral cholesterol ester hydrolase (NCEH), acyl-coenzyme A-cholesterol acyltransferase (ACAT), and reverse cholesterol transport are mutually influential, and form a dynamic process under multi-factor regulation. The macrophage takes on different uptake lipid statuses depending on multiple uptake pathways and intracellular lipids, lipid metabolites versus pro-inflammatory factors. Except for NCEH and ACAT, the lipid internalization of macrophages also depends on multicellular organelles including the lysosome, mitochondria, and endoplasmic reticulum, which are associated with each other. A dynamic balance between esterification and hydrolysis of cholesterol for macrophages is essential for physiology and pathology. Therefore, we propose that the foam cell in the process of atherosclerosis may be dynamic under multi-factor regulation, and collate this study to provide a holistic and dynamic idea of the foam cell.}, } @article {pmid33487113, year = {2021}, author = {Schaap, P}, title = {From environmental sensing to developmental control: cognitive evolution in dictyostelid social amoebas.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {376}, number = {1820}, pages = {20190756}, pmid = {33487113}, issn = {1471-2970}, mesh = {*Biological Evolution ; *Cognition ; Dictyosteliida/*physiology ; *Quorum Sensing ; *Signal Transduction ; }, abstract = {Dictyostelid social amoebas respond to starvation by self-organizing into multicellular slugs that migrate towards light to construct spore-bearing structures. These behaviours depend on excitable networks that enable amoebas to produce propagating waves of the chemoattractant cAMP, and to respond by directional movement. cAMP additionally regulates cell differentiation throughout development, with differentiation and cell movement being coordinated by interaction of the stalk inducer c-di-GMP with the adenylate cyclase that generates cAMP oscillations. Evolutionary studies indicate how the manifold roles of cAMP in multicellular development evolved from a role as intermediate for starvation-induced encystation in the unicellular ancestor. A merger of this stress response with the chemotaxis excitable networks yielded the developmental complexity and cognitive capabilities of extant Dictyostelia. This article is part of the theme issue 'Basal cognition: conceptual tools and the view from the single cell'.}, } @article {pmid33479850, year = {2021}, author = {Tourigny, DS}, title = {Cooperative metabolic resource allocation in spatially-structured systems.}, journal = {Journal of mathematical biology}, volume = {82}, number = {1-2}, pages = {5}, pmid = {33479850}, issn = {1432-1416}, mesh = {Biological Evolution ; Entropy ; Humans ; Models, Biological ; Quorum Sensing ; Resource Allocation ; *Selection, Genetic ; *Social Behavior ; }, abstract = {Natural selection has shaped the evolution of cells and multi-cellular organisms such that social cooperation can often be preferred over an individualistic approach to metabolic regulation. This paper extends a framework for dynamic metabolic resource allocation based on the maximum entropy principle to spatiotemporal models of metabolism with cooperation. Much like the maximum entropy principle encapsulates 'bet-hedging' behaviour displayed by organisms dealing with future uncertainty in a fluctuating environment, its cooperative extension describes how individuals adapt their metabolic resource allocation strategy to further accommodate limited knowledge about the welfare of others within a community. The resulting theory explains why local regulation of metabolic cross-feeding can fulfil a community-wide metabolic objective if individuals take into consideration an ensemble measure of total population performance as the only form of global information. The latter is likely supplied by quorum sensing in microbial systems or signalling molecules such as hormones in multi-cellular eukaryotic organisms.}, } @article {pmid33479022, year = {2021}, author = {Kjellin, J and Avesson, L and Reimegård, J and Liao, Z and Eichinger, L and Noegel, A and Glöckner, G and Schaap, P and Söderbom, F}, title = {Abundantly expressed class of noncoding RNAs conserved through the multicellular evolution of dictyostelid social amoebas.}, journal = {Genome research}, volume = {31}, number = {3}, pages = {436-447}, pmid = {33479022}, issn = {1549-5469}, support = {BB/D013453/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/G020426/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Dictyostelium/classification/*cytology/*genetics ; *Evolution, Molecular ; *Phylogeny ; RNA, Untranslated/*genetics ; }, abstract = {Aggregative multicellularity has evolved multiple times in diverse groups of eukaryotes, exemplified by the well-studied development of dictyostelid social amoebas, for example, Dictyostelium discoideum However, it is still poorly understood why multicellularity emerged in these amoebas while the majority of other members of Amoebozoa are unicellular. Previously, a novel type of noncoding RNA, Class I RNAs, was identified in D. discoideum and shown to be important for normal multicellular development. Here, we investigated Class I RNA evolution and its connection to multicellular development. We identified a large number of new Class I RNA genes by constructing a covariance model combined with a scoring system based on conserved upstream sequences. Multiple genes were predicted in representatives of each major group of Dictyostelia and expression analysis confirmed that our search approach identifies expressed Class I RNA genes with high accuracy and sensitivity and that the RNAs are developmentally regulated. Further studies showed that Class I RNAs are ubiquitous in Dictyostelia and share highly conserved structure and sequence motifs. In addition, Class I RNA genes appear to be unique to dictyostelid social amoebas because they could not be identified in outgroup genomes, including their closest known relatives. Our results show that Class I RNA is an ancient class of ncRNAs, likely to have been present in the last common ancestor of Dictyostelia dating back at least 600 million years. Based on previous functional analyses and the presented evolutionary investigation, we hypothesize that Class I RNAs were involved in evolution of multicellularity in Dictyostelia.}, } @article {pmid33471791, year = {2021}, author = {Miele, L and De Monte, S}, title = {Aggregative cycles evolve as a solution to conflicts in social investment.}, journal = {PLoS computational biology}, volume = {17}, number = {1}, pages = {e1008617}, pmid = {33471791}, issn = {1553-7358}, mesh = {*Biological Evolution ; Cell Aggregation/*physiology ; Cell Movement/*physiology ; Computational Biology ; Dictyostelium/cytology/physiology ; *Models, Biological ; }, abstract = {Multicellular organization is particularly vulnerable to conflicts between different cell types when the body forms from initially isolated cells, as in aggregative multicellular microbes. Like other functions of the multicellular phase, coordinated collective movement can be undermined by conflicts between cells that spend energy in fuelling motion and 'cheaters' that get carried along. The evolutionary stability of collective behaviours against such conflicts is typically addressed in populations that undergo extrinsically imposed phases of aggregation and dispersal. Here, via a shift in perspective, we propose that aggregative multicellular cycles may have emerged as a way to temporally compartmentalize social conflicts. Through an eco-evolutionary mathematical model that accounts for individual and collective strategies of resource acquisition, we address regimes where different motility types coexist. Particularly interesting is the oscillatory regime that, similarly to life cycles of aggregative multicellular organisms, alternates on the timescale of several cell generations phases of prevalent solitary living and starvation-triggered aggregation. Crucially, such self-organized oscillations emerge as a result of evolution of cell traits associated to conflict escalation within multicellular aggregates.}, } @article {pmid33460641, year = {2021}, author = {Schrankel, CS and Hamdoun, A}, title = {Early patterning of ABCB, ABCC, and ABCG transporters establishes unique territories of small molecule transport in embryonic mesoderm and endoderm.}, journal = {Developmental biology}, volume = {472}, number = {}, pages = {115-124}, pmid = {33460641}, issn = {1095-564X}, support = {F32 ES029843/ES/NIEHS NIH HHS/United States ; R01 ES027921/ES/NIEHS NIH HHS/United States ; R01 ES030318/ES/NIEHS NIH HHS/United States ; }, mesh = {ATP-Binding Cassette Transporters/genetics/*metabolism ; Animals ; Biological Transport ; Endoderm/*metabolism ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; In Situ Hybridization ; Intestinal Mucosa/metabolism ; Intestines/embryology ; Mesoderm/*metabolism ; Sea Urchins/*embryology/genetics/metabolism ; Signal Transduction ; }, abstract = {Directed intercellular movement of diverse small molecules, including metabolites, signal molecules and xenobiotics, is a key feature of multicellularity. Networks of small molecule transporters (SMTs), including several ATP Binding Cassette (ABC) transporters, are central to this process. While small molecule transporters are well described in differentiated organs, little is known about their patterns of expression in early embryogenesis. Here we report the pattern of ABC-type SMT expression and activity during the early development of sea urchins. Of the six major ABCs in this embryo (ABCB1, -B4, -C1, -C4, -C5 and -G2), three expression patterns were observed: 1) ABCB1 and ABCC1 are first expressed ubiquitously, and then become enriched in endoderm and ectoderm-derived structures. 2) ABCC4 and ABCC5 are restricted to a ring of mesoderm in the blastula and ABCC4 is later expressed in the coelomic pouches, the embryonic niche of the primordial germ cells. 3) ABCB4 and ABCG2 are expressed exclusively in endoderm-fated cells. Assays with fluorescent substrates and inhibitors of transporters revealed a ring of ABCC4 efflux activity emanating from ABCC4[+] mesodermal cells. Similarly, ABCB1 and ABCB4 efflux activity was observed in the developing gut, prior to the onset of feeding. This study reveals the early establishment of unique territories of small molecule transport during embryogenesis. A pattern of ABCC4/C5 expression is consistent with signaling functions during gut invagination and germ line development, while a later pattern of ABCB1/B4 and ABCG2 is consistent with roles in the embryonic gut. This work provides a conceptual framework with which to examine the function and evolution of SMT networks and to define the specific developmental pathways that drive the expression of these genes.}, } @article {pmid33455859, year = {2021}, author = {Jana, SC}, title = {Centrosome structure and biogenesis: Variations on a theme?.}, journal = {Seminars in cell & developmental biology}, volume = {110}, number = {}, pages = {123-138}, doi = {10.1016/j.semcdb.2020.10.014}, pmid = {33455859}, issn = {1096-3634}, mesh = {Actins/genetics/metabolism ; Animals ; Biodiversity ; Biological Evolution ; Cell Cycle/genetics ; Centrioles/metabolism/*ultrastructure ; Chlorophyta/genetics/metabolism/ultrastructure ; Cilia/metabolism/*ultrastructure ; Eukaryotic Cells/metabolism/ultrastructure ; Gene Expression Regulation ; Humans ; Microtubule-Associated Proteins/classification/*genetics/metabolism ; Microtubules/metabolism/*ultrastructure ; *Organelle Biogenesis ; Species Specificity ; Tubulin/genetics/metabolism ; }, abstract = {Centrosomes are composed of two orthogonally arranged centrioles surrounded by an electron-dense matrix called the pericentriolar material (PCM). Centrioles are cylinders with diameters of ~250 nm, are several hundred nanometres in length and consist of 9-fold symmetrically arranged microtubules (MT). In dividing animal cells, centrosomes act as the principal MT-organising centres and they also organise actin, which tunes cytoplasmic MT nucleation. In some specialised cells, the centrosome acquires additional critical structures and converts into the base of a cilium with diverse functions including signalling and motility. These structures are found in most eukaryotes and are essential for development and homoeostasis at both cellular and organism levels. The ultrastructure of centrosomes and their derived organelles have been known for more than half a century. However, recent advances in a number of techniques have revealed the high-resolution structures (at Å-to-nm scale resolution) of centrioles and have begun to uncover the molecular principles underlying their properties, including: protein components; structural elements; and biogenesis in various model organisms. This review covers advances in our understanding of the features and processes that are critical for the biogenesis of the evolutionarily conserved structures of the centrosomes. Furthermore, it discusses how variations of these aspects can generate diversity in centrosome structure and function among different species and even between cell types within a multicellular organism.}, } @article {pmid33449147, year = {2021}, author = {Kruger, AN and Mueller, JL}, title = {Mechanisms of meiotic drive in symmetric and asymmetric meiosis.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {78}, number = {7}, pages = {3205-3218}, pmid = {33449147}, issn = {1420-9071}, support = {R01 HD094736/HD/NICHD NIH HHS/United States ; T32 GM007544/GM/NIGMS NIH HHS/United States ; T32GM007544/GM/NIGMS NIH HHS/United States ; T32GM007544/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; *Chromosome Segregation ; Humans ; *Meiosis ; Spindle Apparatus/*physiology ; }, abstract = {Meiotic drive, the non-Mendelian transmission of chromosomes to the next generation, functions in asymmetric or symmetric meiosis across unicellular and multicellular organisms. In asymmetric meiosis, meiotic drivers act to alter a chromosome's spatial position in a single egg. In symmetric meiosis, meiotic drivers cause phenotypic differences between gametes with and without the driver. Here we discuss existing models of meiotic drive, highlighting the underlying mechanisms and regulation governing systems for which the most is known. We focus on outstanding questions surrounding these examples and speculate on how new meiotic drive systems evolve and how to detect them.}, } @article {pmid33446527, year = {2021}, author = {Stadler, T and Pybus, OG and Stumpf, MPH}, title = {Phylodynamics for cell biologists.}, journal = {Science (New York, N.Y.)}, volume = {371}, number = {6526}, pages = {}, doi = {10.1126/science.aah6266}, pmid = {33446527}, issn = {1095-9203}, mesh = {Animals ; Caenorhabditis elegans/cytology/growth & development ; Cell Biology/trends ; *Cell Lineage ; Humans ; *Phylogeny ; *Single-Cell Analysis ; Stem Cells/cytology/physiology ; }, abstract = {Multicellular organisms are composed of cells connected by ancestry and descent from progenitor cells. The dynamics of cell birth, death, and inheritance within an organism give rise to the fundamental processes of development, differentiation, and cancer. Technical advances in molecular biology now allow us to study cellular composition, ancestry, and evolution at the resolution of individual cells within an organism or tissue. Here, we take a phylogenetic and phylodynamic approach to single-cell biology. We explain how "tree thinking" is important to the interpretation of the growing body of cell-level data and how ecological null models can benefit statistical hypothesis testing. Experimental progress in cell biology should be accompanied by theoretical developments if we are to exploit fully the dynamical information in single-cell data.}, } @article {pmid33440882, year = {2021}, author = {Takahashi, T}, title = {Multiple Roles for Cholinergic Signaling from the Perspective of Stem Cell Function.}, journal = {International journal of molecular sciences}, volume = {22}, number = {2}, pages = {}, pmid = {33440882}, issn = {1422-0067}, mesh = {Acetylcholine/*metabolism ; Age Factors ; Animals ; Biomarkers ; Brain/cytology/metabolism ; Cell Differentiation/genetics ; Homeostasis ; Humans ; Organ Specificity ; Receptors, Cholinergic/*metabolism ; *Signal Transduction ; Stem Cells/cytology/*metabolism ; }, abstract = {Stem cells have extensive proliferative potential and the ability to differentiate into one or more mature cell types. The mechanisms by which stem cells accomplish self-renewal provide fundamental insight into the origin and design of multicellular organisms. These pathways allow the repair of damage and extend organismal life beyond that of component cells, and they probably preceded the evolution of complex metazoans. Understanding the true nature of stem cells can only come from discovering how they are regulated. The concept that stem cells are controlled by particular microenvironments, also known as niches, has been widely accepted. Technical advances now allow characterization of the zones that maintain and control stem cell activity in several organs, including the brain, skin, and gut. Cholinergic neurons release acetylcholine (ACh) that mediates chemical transmission via ACh receptors such as nicotinic and muscarinic receptors. Although the cholinergic system is composed of organized nerve cells, the system is also involved in mammalian non-neuronal cells, including stem cells, embryonic stem cells, epithelial cells, and endothelial cells. Thus, cholinergic signaling plays a pivotal role in controlling their behaviors. Studies regarding this signal are beginning to unify our understanding of stem cell regulation at the cellular and molecular levels, and they are expected to advance efforts to control stem cells therapeutically. The present article reviews recent findings about cholinergic signaling that is essential to control stem cell function in a cholinergic niche.}, } @article {pmid33421998, year = {2021}, author = {Mondal, M and Peter, J and Scarbrough, O and Flynt, A}, title = {Environmental RNAi pathways in the two-spotted spider mite.}, journal = {BMC genomics}, volume = {22}, number = {1}, pages = {42}, pmid = {33421998}, issn = {1471-2164}, support = {P20 GM103476/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Gene Expression ; Plants ; RNA Interference ; *Tetranychidae/genetics ; }, abstract = {BACKGROUND: RNA interference (RNAi) regulates gene expression in most multicellular organisms through binding of small RNA effectors to target transcripts. Exploiting this process is a popular strategy for genetic manipulation and has applications that includes arthropod pest control. RNAi technologies are dependent on delivery method with the most convenient likely being feeding, which is effective in some animals while others are insensitive. The two-spotted spider mite, Tetranychus urticae, is prime candidate for developing RNAi approaches due to frequent occurrence of conventional pesticide resistance. Using a sequencing-based approach, the fate of ingested RNAs was explored to identify features and conditions that affect small RNA biogenesis from external sources to better inform RNAi design.

RESULTS: Biochemical and sequencing approaches in conjunction with extensive computational assessment were used to evaluate metabolism of ingested RNAs in T. urticae. This chelicerae arthropod shows only modest response to oral RNAi and has biogenesis pathways distinct from model organisms. Processing of synthetic and plant host RNAs ingested during feeding were evaluated to identify active substrates for spider mite RNAi pathways. Through cataloging characteristics of biochemically purified RNA from these sources, trans-acting small RNAs could be distinguished from degradation fragments and their origins documented.

CONCLUSIONS: Using a strategy that delineates small RNA processing, we found many transcripts have the potential to enter spider mite RNAi pathways, however, trans-acting RNAs appear very unstable and rare. This suggests potential RNAi pathway substrates from ingested materials are mostly degraded and infrequently converted into regulators of gene expression. Spider mites infest a variety of plants, and it would be maladaptive to generate diverse gene regulators from dietary RNAs. This study provides a framework for assessing RNAi technology in organisms where genetic and biochemical tools are absent and benefit rationale design of RNAi triggers for T.urticae.}, } @article {pmid33418487, year = {2021}, author = {Sagova-Mareckova, M and Boenigk, J and Bouchez, A and Cermakova, K and Chonova, T and Cordier, T and Eisendle, U and Elersek, T and Fazi, S and Fleituch, T and Frühe, L and Gajdosova, M and Graupner, N and Haegerbaeumer, A and Kelly, AM and Kopecky, J and Leese, F and Nõges, P and Orlic, S and Panksep, K and Pawlowski, J and Petrusek, A and Piggott, JJ and Rusch, JC and Salis, R and Schenk, J and Simek, K and Stovicek, A and Strand, DA and Vasquez, MI and Vrålstad, T and Zlatkovic, S and Zupancic, M and Stoeck, T}, title = {Expanding ecological assessment by integrating microorganisms into routine freshwater biomonitoring.}, journal = {Water research}, volume = {191}, number = {}, pages = {116767}, doi = {10.1016/j.watres.2020.116767}, pmid = {33418487}, issn = {1879-2448}, mesh = {Archaea/genetics ; *Biological Monitoring ; *Ecosystem ; Environmental Biomarkers ; Environmental Monitoring ; Fresh Water ; }, abstract = {Bioindication has become an indispensable part of water quality monitoring in most countries of the world, with the presence and abundance of bioindicator taxa, mostly multicellular eukaryotes, used for biotic indices. In contrast, microbes (bacteria, archaea and protists) are seldom used as bioindicators in routine assessments, although they have been recognized for their importance in environmental processes. Recently, the use of molecular methods has revealed unexpected diversity within known functional groups and novel metabolic pathways that are particularly important in energy and nutrient cycling. In various habitats, microbial communities respond to eutrophication, metals, and natural or anthropogenic organic pollutants through changes in diversity and function. In this review, we evaluated the common trends in these changes, documenting that they have value as bioindicators and can be used not only for monitoring but also for improving our understanding of the major processes in lotic and lentic environments. Current knowledge provides a solid foundation for exploiting microbial taxa, community structures and diversity, as well as functional genes, in novel monitoring programs. These microbial community measures can also be combined into biotic indices, improving the resolution of individual bioindicators. Here, we assess particular molecular approaches complemented by advanced bioinformatic analysis, as these are the most promising with respect to detailed bioindication value. We conclude that microbial community dynamics are a missing link important for our understanding of rapid changes in the structure and function of aquatic ecosystems, and should be addressed in the future environmental monitoring of freshwater ecosystems.}, } @article {pmid33412387, year = {2021}, author = {Liu, Q and Piao, H and Wang, Y and Zheng, D and Wang, W}, title = {Circulating exosomes in cardiovascular disease: Novel carriers of biological information.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {135}, number = {}, pages = {111148}, doi = {10.1016/j.biopha.2020.111148}, pmid = {33412387}, issn = {1950-6007}, mesh = {Animals ; Biomarkers/metabolism ; Cardiovascular Diseases/blood/genetics/*metabolism/therapy ; Cardiovascular System/*metabolism ; *Cell Communication ; Drug Carriers ; Exosomes/genetics/*metabolism/transplantation ; Gene Transfer Techniques ; Genetic Therapy ; Humans ; Signal Transduction ; }, abstract = {Exosomes are a group of nanosized extracellular vesicles that include various bioactive nucleic acids, lipids, and proteins. They originate from membrane invagination and are released by exocytosis, which can transmit signals to target cells to achieve cell-to-cell communication and maintain homeostasis. The heart is a complex multicellular organ that contains resident cell types such as fibroblasts, endothelial cells, and smooth muscle cells. Communication between different cell types and immune systems is essential for the dynamic equilibrium of the cardiac internal environment. Intercellular communication is a universal phenomenon mediated by exosomes and their contents during several pathological processes in cardiovascular diseases, such as cardiomyocyte hypertrophy, apoptosis, and angiogenesis. Therefore, exosomes can be used as novel invasive diagnostic biomarkers in multiple diseases, including atherosclerosis, myocardial ischemia, cardiac fibrosis, and ischemia-reperfusion injury. In addition, the biocompatible nature and low immunogenicity of exosomes make them high-quality nanoparticle drug carriers with potential applications in translational medicine and therapeutic strategies. Here, we focus on the biogenesis, isolation, biological functions, and future application prospects of exosomes in cardiovascular disease.}, } @article {pmid33411582, year = {2021}, author = {Costa, M and Blaschke, TF and Amara, SG and Meyer, UA and Insel, PA}, title = {Introduction to the Theme "Old and New Toxicology: Interfaces with Pharmacology".}, journal = {Annual review of pharmacology and toxicology}, volume = {61}, number = {}, pages = {1-7}, doi = {10.1146/annurev-pharmtox-092220-033032}, pmid = {33411582}, issn = {1545-4304}, mesh = {Female ; Humans ; Male ; *Pharmacology ; *Toxicology ; }, abstract = {The theme of Volume 61 is "Old and New Toxicology: Interfaces with Pharmacology." Old toxicology is exemplified by the authors of the autobiographical articles: B.M. Olivera's work on toxins and venoms from cone snails and P. Taylor's studies of acetylcholinesterase and the nicotinic cholinergic receptor, which serve as sites of action for numerous pesticides and venoms. Other articles in this volume focus on new understanding and new types of toxicology, including (a) arsenic toxicity, which is an ancient poison that, through evolution, has caused most multicellular organisms to express an active arsenic methyltransferase to methylate arsenite, which accelerates the excretion of arsenic from the body; (b) small molecules that react with lipid dicarbonyls, which are now considered the most toxic oxidative stress end products; (c) immune checkpoint inhibitors (ICIs), which have revolutionized cancer therapy but have numerous immune-related adverse events, including cardiovascular complications; (d) autoimmunity caused by the environment; (e) idiosyncratic drug-induced liver disease, which together with the toxicity of ICIs represents new toxicology interfacing with pharmacology; and (f) sex differences in the development of cardiovascular disease, with men more susceptible than women to vascular inflammation that initiates and perpetuates disease. These articles and others in Volume 61 reflect the interface and close integration of pharmacology and toxicology that began long ago but continues today.}, } @article {pmid33397407, year = {2021}, author = {Bourdareau, S and Tirichine, L and Lombard, B and Loew, D and Scornet, D and Wu, Y and Coelho, SM and Cock, JM}, title = {Histone modifications during the life cycle of the brown alga Ectocarpus.}, journal = {Genome biology}, volume = {22}, number = {1}, pages = {12}, pmid = {33397407}, issn = {1474-760X}, mesh = {Chromatin/metabolism ; Epigenesis, Genetic ; Genome ; Germ Cells, Plant ; *Histone Code ; *Histones ; *Life Cycle Stages ; Phaeophyta/*genetics/physiology ; Phylogeny ; Plants/genetics ; *Protein Processing, Post-Translational ; }, abstract = {BACKGROUND: Brown algae evolved complex multicellularity independently of the animal and land plant lineages and are the third most developmentally complex phylogenetic group on the planet. An understanding of developmental processes in this group is expected to provide important insights into the evolutionary events necessary for the emergence of complex multicellularity. Here, we focus on mechanisms of epigenetic regulation involving post-translational modifications of histone proteins.

RESULTS: A total of 47 histone post-translational modifications are identified, including a novel mark H2AZR38me1, but Ectocarpus lacks both H3K27me3 and the major polycomb complexes. ChIP-seq identifies modifications associated with transcription start sites and gene bodies of active genes and with transposons. H3K79me2 exhibits an unusual pattern, often marking large genomic regions spanning several genes. Transcription start sites of closely spaced, divergently transcribed gene pairs share a common nucleosome-depleted region and exhibit shared histone modification peaks. Overall, patterns of histone modifications are stable through the life cycle. Analysis of histone modifications at generation-biased genes identifies a correlation between the presence of specific chromatin marks and the level of gene expression.

CONCLUSIONS: The overview of histone post-translational modifications in the brown alga presented here will provide a foundation for future studies aimed at understanding the role of chromatin modifications in the regulation of brown algal genomes.}, } @article {pmid33389562, year = {2021}, author = {Furumizu, C and Sawa, S}, title = {Insight into early diversification of leucine-rich repeat receptor-like kinases provided by the sequenced moss and hornwort genomes.}, journal = {Plant molecular biology}, volume = {107}, number = {4-5}, pages = {337-353}, pmid = {33389562}, issn = {1573-5028}, mesh = {Amino Acid Sequence ; Anthocerotophyta/*genetics ; Computer Simulation ; Evolution, Molecular ; *Genetic Variation ; Genome, Plant/*genetics ; Genomics/methods ; Phylogeny ; Plant Proteins/chemistry/classification/*genetics ; Protein Domains ; Protein Kinases/chemistry/classification/*genetics ; Sequence Homology, Amino Acid ; Signal Transduction/genetics ; Sphagnopsida/*genetics ; }, abstract = {Identification of the subfamily X leucine-rich repeat receptor-like kinases in the recently sequenced moss and hornwort genomes points to their diversification into distinct groups during early evolution of land plants. Signal transduction mediated through receptor-ligand interactions plays key roles in controlling developmental and physiological processes of multicellular organisms, and plants employ diverse receptors in signaling. Leucine-rich repeat receptor-like kinases (LRR-RLKs) represent one of the largest receptor classes in plants and are structurally classified into subfamilies. LRR-RLKs of the subfamily X are unique in the variety of their signaling roles; they include receptors for steroid or peptide hormones as well as negative regulators of signaling through binding to other LRR-RLKs, raising a question as to how they diversified. However, our understanding of diversification processes of LRR-RLKs has been hindered by the paucity of genomic data in non-seed plants and limited taxa sampling in previous phylogenetic analyses. Here we analyzed the phylogeny of LRR-RLK X sequences collected from all major land plant lineages and show that this subfamily diversified into six major clades before the divergence between bryophytes and vascular plants. Notably, we have identified homologues of the brassinosteroid receptor, BRASSINOSTEROID INSENSITIVE 1 (BRI1), in the genomes of Sphagnum mosses, hornworts, and ferns, contrary to earlier reports that postulate the origin of BRI1-like LRR-RLKs in the seed plant lineage. The phylogenetic distribution of major clades illustrates that the current receptor repertoire was shaped through lineage-specific gene family expansion and independent gene losses, highlighting dynamic changes in the evolution of LRR-RLKs.}, } @article {pmid33373044, year = {2021}, author = {Montoro, R and Heine, VM and Kemp, S and Engelen, M}, title = {Evolution of adrenoleukodystrophy model systems.}, journal = {Journal of inherited metabolic disease}, volume = {44}, number = {3}, pages = {544-553}, pmid = {33373044}, issn = {1573-2665}, mesh = {ATP Binding Cassette Transporter, Subfamily D, Member 1/*genetics ; Adrenoleukodystrophy/epidemiology/*genetics ; Adult ; Animals ; Biological Evolution ; Fatty Acids/metabolism ; Female ; Humans ; Male ; *Models, Animal ; *Models, Biological ; Mutation ; Sex Factors ; Spinal Cord Diseases/epidemiology ; }, abstract = {X-linked adrenoleukodystrophy (ALD) is a neurometabolic disorder affecting the adrenal glands, testes, spinal cord and brain. The disease is caused by mutations in the ABCD1 gene resulting in a defect in peroxisomal degradation of very long-chain fatty acids and their accumulation in plasma and tissues. Males with ALD have a near 100% life-time risk to develop myelopathy. The life-time prevalence to develop progressive cerebral white matter lesions (known as cerebral ALD) is about 60%. Adrenal insufficiency occurs in about 80% of male patients. In adulthood, 80% of women with ALD also develop myelopathy, but adrenal insufficiency or cerebral ALD are very rare. The complex clinical presentation and the absence of a genotype-phenotype correlation are complicating our understanding of the disease. In an attempt to understand the pathophysiology of ALD various model systems have been developed. While these model systems share the basic genetics and biochemistry of ALD they fail to fully recapitulate the complex neurodegenerative etiology of ALD. Each model system recapitulates certain aspects of the disorder. This exposes the complexity of ALD and therefore the challenge to create a comprehensive model system to fully understand ALD. In this review, we provide an overview of the different ALD modeling strategies from single-celled to multicellular organisms and from in vitro to in vivo approaches, and introduce how emerging iPSC-derived technologies could improve the understanding of this highly complex disorder.}, } @article {pmid33355212, year = {2021}, author = {Stresser, DM and Sun, J and Wilson, SS}, title = {Evaluation of Tissue Stem Cell-Derived Human Intestinal Organoids, a Physiologically Relevant Model to Evaluate Cytochrome P450 Induction in Gut.}, journal = {Drug metabolism and disposition: the biological fate of chemicals}, volume = {49}, number = {3}, pages = {245-253}, doi = {10.1124/dmd.120.000281}, pmid = {33355212}, issn = {1521-009X}, mesh = {Cell Line ; Cytochrome P-450 Enzyme Inducers/*pharmacology ; Cytochrome P-450 Enzyme System/*biosynthesis ; Dose-Response Relationship, Drug ; Enzyme Induction/drug effects/physiology ; Humans ; Intestines/cytology/drug effects/*enzymology ; Organoids/drug effects/*enzymology ; Rifampin/pharmacology ; Stem Cells/drug effects/*enzymology ; }, abstract = {Induction of cytochrome P450 can cause drug-drug interactions and efficacy failure. Induction risk in liver and gut is typically inferred from experiments with plated hepatocytes. Organoids are physiologically relevant, multicellular structures originating from stem cells. Intestinal stem cell-derived organoids retain traits of normal gut physiology, such as an epithelial barrier and cellular diversity. Matched human enteroid and colonoid lines, generated from ileal and colon biopsies from two donors, were cultured in extracellular matrix for 3 days, followed by a single 48-hour treatment with rifampin, omeprazole, CITCO, and phenytoin at concentrations that induce target genes in hepatocytes. After treatment, mRNA was analyzed for induction of target genes. Rifampin induced CYP3A4; estimated EC50 and maximal fold induction were 3.75 µM and 8.96-fold, respectively, for ileal organoids and 1.40 µM and 11.3-fold, respectively, for colon organoids. Ileal, but not colon, organoids exhibited nifedipine oxidase activity, which was induced by rifampin up to 14-fold. The test compounds did not increase mRNA expression of CYP1A2, CYP2B6, multidrug resistance transporter 1 (P-glycoprotein), breast cancer resistance protein, and UDP-glucuronosyltransferase 1A1 in ileal organoids. Whereas omeprazole induced CYP3A4 (up to 5.3-fold, geometric mean, n = 4 experiments), constitutive androstane receptor activators phenytoin and CITCO did not. Omeprazole failed to induce CYP1A2 mRNA but did induce CYP1A1 mRNA (up to 7.7-fold and 15-fold in ileal and colon organoids, respectively, n = 4 experiments). Despite relatively high intra- and interexperimental variability, data suggest that the model yields induction responses that are distinct from hepatocytes and holds promise to enable evaluation of CYP1A1 and CYP3A4 induction in gut. SIGNIFICANCE STATEMENT: An adult intestinal stem cell-derived organoid model to test P450 induction in gut was evaluated. Testing several prototypical inducers for mRNA induction of P450 isoforms, UDP-glucuronosyltransferase 1A1, P-glycoprotein, and breast cancer resistance protein with both human colon and ileal organoids resulted in a range of responses, often distinct from those found in hepatocytes, indicating the potential for further development of this model as a physiologically relevant gut induction test system.}, } @article {pmid33354870, year = {2021}, author = {Fritsche, E and Haarmann-Stemmann, T and Kapr, J and Galanjuk, S and Hartmann, J and Mertens, PR and Kämpfer, AAM and Schins, RPF and Tigges, J and Koch, K}, title = {Stem Cells for Next Level Toxicity Testing in the 21st Century.}, journal = {Small (Weinheim an der Bergstrasse, Germany)}, volume = {17}, number = {15}, pages = {e2006252}, doi = {10.1002/smll.202006252}, pmid = {33354870}, issn = {1613-6829}, mesh = {Humans ; In Vitro Techniques ; *Induced Pluripotent Stem Cells ; *Toxicity Tests ; United States ; }, abstract = {The call for a paradigm change in toxicology from the United States National Research Council in 2007 initiates awareness for the invention and use of human-relevant alternative methods for toxicological hazard assessment. Simple 2D in vitro systems may serve as first screening tools, however, recent developments infer the need for more complex, multicellular organotypic models, which are superior in mimicking the complexity of human organs. In this review article most critical organs for toxicity assessment, i.e., skin, brain, thyroid system, lung, heart, liver, kidney, and intestine are discussed with regards to their functions in health and disease. Embracing the manifold modes-of-action how xenobiotic compounds can interfere with physiological organ functions and cause toxicity, the need for translation of such multifaceted organ features into the dish seems obvious. Currently used in vitro methods for toxicological applications and ongoing developments not yet arrived in toxicity testing are discussed, especially highlighting the potential of models based on embryonic stem cells and induced pluripotent stem cells of human origin. Finally, the application of innovative technologies like organs-on-a-chip and genome editing point toward a toxicological paradigm change moves into action.}, } @article {pmid33305692, year = {2020}, author = {Giam, M and Wong, CK and Low, JS and Sinelli, M and Dreesen, O and Rancati, G}, title = {P53 induces senescence in the unstable progeny of aneuploid cells.}, journal = {Cell cycle (Georgetown, Tex.)}, volume = {19}, number = {24}, pages = {3508-3520}, pmid = {33305692}, issn = {1551-4005}, mesh = {*Aneuploidy ; Cell Cycle Checkpoints/genetics ; Cell Proliferation/genetics ; Cell Transformation, Neoplastic/genetics/metabolism ; Cellular Senescence/*genetics ; Chromosomal Instability/genetics ; Chromosome Segregation/genetics ; Epithelial Cells/*metabolism ; Gene Knockdown Techniques ; HEK293 Cells ; Humans ; Karyotype ; Retinal Pigment Epithelium/*cytology ; Tumor Suppressor Protein p53/genetics/*metabolism ; }, abstract = {Aneuploidy is the condition of having an imbalanced karyotype, which is associated with tumor initiation, evolution, and acquisition of drug-resistant features, possibly by generating heterogeneous populations of cells with distinct genotypes and phenotypes. Multicellular eukaryotes have therefore evolved a range of extrinsic and cell-autonomous mechanisms for restraining proliferation of aneuploid cells, including activation of the tumor suppressor protein p53. However, accumulating evidence indicates that a subset of aneuploid cells can escape p53-mediated growth restriction and continue proliferating in vitro. Here we show that such aneuploid cell lines display a robust modal karyotype and low frequency of chromosomal aberrations despite ongoing chromosome instability. Indeed, while these aneuploid cells are able to survive for extended periods in vitro, their chromosomally unstable progeny remain subject to p53-induced senescence and growth restriction, leading to subsequent elimination from the aneuploid pool. This mechanism helps maintain low levels of heterogeneity in aneuploid populations and may prevent detrimental evolutionary processes such as cancer progression and development of drug resistance.}, } @article {pmid33272929, year = {2020}, author = {Ruiz-Trillo, I and de Mendoza, A}, title = {Towards understanding the origin of animal development.}, journal = {Development (Cambridge, England)}, volume = {147}, number = {23}, pages = {}, doi = {10.1242/dev.192575}, pmid = {33272929}, issn = {1477-9129}, mesh = {Animals ; *Biological Evolution ; Choanoflagellata/genetics/*growth & development ; Embryonic Development/*genetics ; Gene Expression Regulation, Developmental/genetics ; Mammals/genetics ; Morphogenesis/*genetics ; Phylogeny ; Zygote/growth & development ; }, abstract = {Almost all animals undergo embryonic development, going from a single-celled zygote to a complex multicellular adult. We know that the patterning and morphogenetic processes involved in development are deeply conserved within the animal kingdom. However, the origins of these developmental processes are just beginning to be unveiled. Here, we focus on how the protist lineages sister to animals are reshaping our view of animal development. Most intriguingly, many of these protistan lineages display transient multicellular structures, which are governed by similar morphogenetic and gene regulatory processes as animal development. We discuss here two potential alternative scenarios to explain the origin of animal embryonic development: either it originated concomitantly at the onset of animals or it evolved from morphogenetic processes already present in their unicellular ancestors. We propose that an integrative study of several unicellular taxa closely related to animals will allow a more refined picture of how the last common ancestor of animals underwent embryonic development.}, } @article {pmid33266251, year = {2020}, author = {Lyall, R and Nikoloski, Z and Gechev, T}, title = {Comparative Analysis of ROS Network Genes in Extremophile Eukaryotes.}, journal = {International journal of molecular sciences}, volume = {21}, number = {23}, pages = {}, pmid = {33266251}, issn = {1422-0067}, mesh = {Biomarkers ; Eukaryota/*genetics/*metabolism ; Extremophiles/*genetics/*metabolism ; Gene Expression Regulation ; Gene Expression Regulation, Enzymologic ; *Gene Regulatory Networks ; Oxidative Stress ; Plants/genetics/metabolism ; Reactive Oxygen Species/*metabolism ; }, abstract = {The reactive oxygen species (ROS) gene network, consisting of both ROS-generating and detoxifying enzymes, adjusts ROS levels in response to various stimuli. We performed a cross-kingdom comparison of ROS gene networks to investigate how they have evolved across all Eukaryotes, including protists, fungi, plants and animals. We included the genomes of 16 extremotolerant Eukaryotes to gain insight into ROS gene evolution in organisms that experience extreme stress conditions. Our analysis focused on ROS genes found in all Eukaryotes (such as catalases, superoxide dismutases, glutathione reductases, peroxidases and glutathione peroxidase/peroxiredoxins) as well as those specific to certain groups, such as ascorbate peroxidases, dehydroascorbate/monodehydroascorbate reductases in plants and other photosynthetic organisms. ROS-producing NADPH oxidases (NOX) were found in most multicellular organisms, although several NOX-like genes were identified in unicellular or filamentous species. However, despite the extreme conditions experienced by extremophile species, we found no evidence for expansion of ROS-related gene families in these species compared to other Eukaryotes. Tardigrades and rotifers do show ROS gene expansions that could be related to their extreme lifestyles, although a high rate of lineage-specific horizontal gene transfer events, coupled with recent tetraploidy in rotifers, could explain this observation. This suggests that the basal Eukaryotic ROS scavenging systems are sufficient to maintain ROS homeostasis even under the most extreme conditions.}, } @article {pmid33263876, year = {2020}, author = {Kaczanowski, S}, title = {Symbiotic Origin of Apoptosis.}, journal = {Results and problems in cell differentiation}, volume = {69}, number = {}, pages = {253-280}, pmid = {33263876}, issn = {0080-1844}, mesh = {Animals ; *Apoptosis ; *Biological Evolution ; *Eukaryota ; Mitochondria/*microbiology ; Phylogeny ; *Symbiosis ; }, abstract = {The progress of evolutionary biology has revealed that symbiosis played a basic role in the evolution of complex eukaryotic organisms, including humans. Mitochondria are actually simplified endosymbiotic bacteria currently playing the role of cellular organelles. Mitochondrial domestication occurred at the very beginning of eukaryotic evolution. Mitochondria have two different basic functions: they produce energy using oxidative respiration, and they initiate different forms of apoptotic programmed/regulated cell death. Apoptotic programmed cell death may have different cytological forms. Mechanisms of apoptotic programmed cell death exist even in the unicellular organisms, and they play a basic role in the development of complex multicellular organisms, such as fungi, green plants, and animals. Multicellularity was independently established many times among eukaryotes. There are indications that apoptotic programmed cell death is a trait required for the establishment of multicellularity. Regulated cell death is initiated by many different parallel biochemical pathways. It is generally accepted that apoptosis evolved during mitochondrial domestication. However, there are different hypothetical models of the origin of apoptosis. The phylogenetic studies of my group indicate that apoptosis probably evolved during an evolutionary arms race between host ancestral eukaryotic predators and ancestral prey mitochondria (named protomitochondria). Protomitochondrial prey produced many different toxins as a defense against predators. From these toxins evolved extant apoptotic factors. There are indications that aerobic respiration and apoptosis co-evolved and are functionally linked in extant organisms. Perturbations of apoptosis and oxidative respiration are frequently observed during neoplastic transition. Our group showed that perturbations of apoptosis in yeasts also cause perturbations of oxidative respiration.}, } @article {pmid33262337, year = {2020}, author = {McEvoy, E and Han, YL and Guo, M and Shenoy, VB}, title = {Gap junctions amplify spatial variations in cell volume in proliferating tumor spheroids.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {6148}, pmid = {33262337}, issn = {2041-1723}, support = {R01 CA232256/CA/NCI NIH HHS/United States ; R01 EB017753/EB/NIBIB NIH HHS/United States ; R01 EB030876/EB/NIBIB NIH HHS/United States ; }, mesh = {Breast Neoplasms/chemistry/pathology/*physiopathology ; Cell Line, Tumor ; *Cell Proliferation ; Cell Size ; Disease Progression ; Female ; Gap Junctions/*chemistry ; Humans ; Osmotic Pressure ; Spheroids, Cellular/chemistry/*cytology ; }, abstract = {Sustained proliferation is a significant driver of cancer progression. Cell-cycle advancement is coupled with cell size, but it remains unclear how multiple cells interact to control their volume in 3D clusters. In this study, we propose a mechano-osmotic model to investigate the evolution of volume dynamics within multicellular systems. Volume control depends on an interplay between multiple cellular constituents, including gap junctions, mechanosensitive ion channels, energy-consuming ion pumps, and the actomyosin cortex, that coordinate to manipulate cellular osmolarity. In connected cells, we show that mechanical loading leads to the emergence of osmotic pressure gradients between cells with consequent increases in cellular ion concentrations driving swelling. We identify how gap junctions can amplify spatial variations in cell volume within multicellular spheroids and, further, describe how the process depends on proliferation-induced solid stress. Our model may provide new insight into the role of gap junctions in breast cancer progression.}, } @article {pmid33259762, year = {2020}, author = {König, SG and Nedelcu, AM}, title = {The genetic basis for the evolution of soma: mechanistic evidence for the co-option of a stress-induced gene into a developmental master regulator.}, journal = {Proceedings. Biological sciences}, volume = {287}, number = {1940}, pages = {20201414}, pmid = {33259762}, issn = {1471-2954}, mesh = {*Biological Evolution ; Chlorophyta/*genetics ; Clonal Evolution/*genetics ; Stress, Physiological/*genetics ; }, abstract = {In multicellular organisms with specialized cells, the most significant distinction among cell types is between reproductive (germ) cells and non-reproductive/somatic cells (soma). Although soma contributed to the marked increase in complexity of many multicellular lineages, little is known about its evolutionary origins. We have previously suggested that the evolution of genes responsible for the differentiation of somatic cells involved the co-option of life history trade-off genes that in unicellular organisms enhanced survival at a cost to immediate reproduction. In the multicellular green alga, Volvox carteri, cell fate is established early in development by the differential expression of a master regulatory gene known as regA. A closely related RegA-Like Sequence (RLS1) is present in its single-celled relative, Chlamydomonas reinhardtii. RLS1 is expressed in response to stress, and we proposed that an environmentally induced RLS1-like gene was co-opted into a developmental pathway in the lineage leading to V. carteri. However, the exact evolutionary scenario responsible for the postulated co-option event remains to be determined. Here, we show that in addition to being developmentally regulated, regA can also be induced by environmental cues, indicating that regA has maintained its ancestral regulation. We also found that the absence of a functional RegA protein confers increased sensitivity to stress, consistent with RegA having a direct or indirect role in stress responses. Overall, this study (i) provides mechanistic evidence for the co-option of an environmentally induced gene into a major developmental regulator, (ii) supports the view that major morphological innovations can evolve via regulatory changes and (iii) argues for the role of stress in the evolution of multicellular complexity.}, } @article {pmid33254563, year = {2020}, author = {Retzinger, AC and Retzinger, GS}, title = {Mites, ticks, anaphylaxis and allergy: The Acari hypothesis.}, journal = {Medical hypotheses}, volume = {144}, number = {}, pages = {110257}, doi = {10.1016/j.mehy.2020.110257}, pmid = {33254563}, issn = {1532-2777}, mesh = {Allergens ; *Anaphylaxis ; Animals ; *Food Hypersensitivity ; Humans ; Immunoglobulin E ; *Mites ; *Ticks ; }, abstract = {Anaphylaxis is a poorly understood immune process in which a Th2-/IgE-mediated adaptive response commandeers cellular machinery, typically reserved for defense against multicellular ectoparasites, to activate against otherwise benign molecules. Its clinical manifestations consist of rapid pathophysiological reflexes that target epithelial surfaces. The galactose-α-1,3-galactose hypersensitivity response is a compelling model of anaphylaxis for which causation has been demonstrated. At the core of the model, a tick bite sensitizes a recipient to a tick foodstuff. As proposed herein, the model likely informs on the origin of all allergic inflammation; namely, allergy is not intended to protect against seemingly harmless and irrelevant materials, but is, instead, intended to rid epithelial surfaces of pathogen-bearing Acari, i.e., mites and ticks. The demonstrated adjuvant activity of acarian gastrointestinal secretions, when paired with the polyphagous diet of mites, renders acarians eminently suited to accounting, mechanistically, for many, if not all, human allergies.}, } @article {pmid33248278, year = {2020}, author = {Chi, S and Wang, G and Liu, T and Wang, X and Liu, C and Jin, Y and Yin, H and Xu, X and Yu, J}, title = {Transcriptomic and Proteomic Analysis of Mannitol-metabolism-associated Genes in Saccharina japonica.}, journal = {Genomics, proteomics & bioinformatics}, volume = {18}, number = {4}, pages = {415-429}, pmid = {33248278}, issn = {2210-3244}, mesh = {*Laminaria ; Mannitol ; *Phaeophyta/genetics ; Proteomics ; Transcriptome ; }, abstract = {As a carbon-storage compound and osmoprotectant in brown algae, mannitol is synthesized and then accumulated at high levels in Saccharina japonica (Sja); however, the underlying control mechanisms have not been studied. Our analysis of genomic and transcriptomic data from Sja shows that mannitol metabolism is a cyclic pathway composed of four distinct steps. A mannitol-1-phosphate dehydrogenase (M1PDH2) and two mannitol-1-phosphatases (M1Pase1 and MIPase2) work together or in combination to exhibit full enzymatic properties. Based on comprehensive transcriptomic data from different tissues, generations, and sexes as well as under different stress conditions, coupled with droplet digital PCR (ddPCR) and proteomic confirmation, we suggest that SjaM1Pase1 plays a major role in mannitol biosynthesis and that the basic mannitol anabolism and the carbohydrate pool dynamics are responsible for carbon storage and anti-stress mechanism. Our proteomic data indicate that mannitol metabolism remains constant during diurnal cycle in Sja. In addition, we discover that mannitol-metabolism-associated (MMA) genes show differential expression between the multicellular filamentous (gametophyte) and large parenchymal thallus (sporophyte) generations and respond differentially to environmental stresses, such as hyposaline and hyperthermia conditions. Our results indicate that the ecophysiological significance of such differentially expressed genes may be attributable to the evolution of heteromorphic generations (filamentous and thallus) and environmental adaptation of Laminariales.}, } @article {pmid33239636, year = {2020}, author = {Xu, Z and Wang, S and Zhao, C and Li, S and Liu, X and Wang, L and Li, M and Huang, X and Mann, S}, title = {Photosynthetic hydrogen production by droplet-based microbial micro-reactors under aerobic conditions.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {5985}, pmid = {33239636}, issn = {2041-1723}, mesh = {Aerobiosis/physiology ; Bioreactors/*microbiology ; Cell Hypoxia/physiology ; Chlorella/metabolism ; Escherichia coli/metabolism ; Hydrogen/*metabolism ; Industrial Microbiology/*methods ; Microbiota/*physiology ; Oxygen/*metabolism ; Photosynthesis/physiology ; Renewable Energy ; }, abstract = {The spontaneous self-assembly of multicellular ensembles into living materials with synergistic structure and function remains a considerable challenge in biotechnology and synthetic biology. Here, we exploit the aqueous two-phase separation of dextran-in-PEG emulsion micro-droplets for the capture, spatial organization and immobilization of algal cells or algal/bacterial cell communities to produce discrete multicellular spheroids capable of both aerobic (oxygen producing) and hypoxic (hydrogen producing) photosynthesis in daylight under air. We show that localized oxygen depletion results in hydrogen production from the core of the algal microscale reactor, and demonstrate that enhanced levels of hydrogen evolution can be achieved synergistically by spontaneously enclosing the photosynthetic cells within a shell of bacterial cells undergoing aerobic respiration. Our results highlight a promising droplet-based environmentally benign approach to dispersible photosynthetic microbial micro-reactors comprising segregated cellular micro-niches with dual functionality, and provide a step towards photobiological hydrogen production under aerobic conditions.}, } @article {pmid33228413, year = {2020}, author = {Coelho, SM and Cock, JM}, title = {Brown Algal Model Organisms.}, journal = {Annual review of genetics}, volume = {54}, number = {}, pages = {71-92}, doi = {10.1146/annurev-genet-030620-093031}, pmid = {33228413}, issn = {1545-2948}, mesh = {Animals ; Genome/genetics ; Humans ; Models, Biological ; Phaeophyta/*genetics ; Phylogeny ; }, abstract = {Model organisms are extensively used in research as accessible and convenient systems for studying a particular area or question in biology. Traditionally, only a limited number of organisms have been studied in detail, but modern genomic tools are enabling researchers to extend beyond the set of classical model organisms to include novel species from less-studied phylogenetic groups. This review focuses on model species for an important group of multicellular organisms, the brown algae. The development of genetic and genomic tools for the filamentous brown alga Ectocarpus has led to it emerging as a general model system for this group, but additional models, such as Fucus or Dictyota dichotoma, remain of interest for specific biological questions. In addition, Saccharina japonica has emerged as a model system to directly address applied questions related to algal aquaculture. We discuss the past, present, and future of brown algal model organisms in relation to the opportunities and challenges in brown algal research.}, } @article {pmid33228223, year = {2020}, author = {Anatskaya, OV and Vinogradov, AE and Vainshelbaum, NM and Giuliani, A and Erenpreisa, J}, title = {Phylostratic Shift of Whole-Genome Duplications in Normal Mammalian Tissues towards Unicellularity Is Driven by Developmental Bivalent Genes and Reveals a Link to Cancer.}, journal = {International journal of molecular sciences}, volume = {21}, number = {22}, pages = {}, pmid = {33228223}, issn = {1422-0067}, mesh = {Animals ; Antineoplastic Agents/therapeutic use ; Carcinogenesis/*genetics/metabolism/pathology ; Circadian Rhythm Signaling Peptides and Proteins/genetics/metabolism ; Drug Resistance, Neoplasm/genetics ; Epigenesis, Genetic ; Gene Duplication ; *Gene Expression Regulation, Neoplastic ; *Genome ; Humans ; Metabolic Networks and Pathways/genetics ; Mice ; Neoplasm Proteins/*genetics/metabolism ; Neoplasms/drug therapy/*genetics/metabolism/pathology ; Oncogenes ; *Ploidies ; Protein Interaction Mapping ; Proto-Oncogene Proteins c-myc/genetics/metabolism ; }, abstract = {Tumours were recently revealed to undergo a phylostratic and phenotypic shift to unicellularity. As well, aggressive tumours are characterized by an increased proportion of polyploid cells. In order to investigate a possible shared causation of these two features, we performed a comparative phylostratigraphic analysis of ploidy-related genes, obtained from transcriptomic data for polyploid and diploid human and mouse tissues using pairwise cross-species transcriptome comparison and principal component analysis. Our results indicate that polyploidy shifts the evolutionary age balance of the expressed genes from the late metazoan phylostrata towards the upregulation of unicellular and early metazoan phylostrata. The up-regulation of unicellular metabolic and drug-resistance pathways and the downregulation of pathways related to circadian clock were identified. This evolutionary shift was associated with the enrichment of ploidy with bivalent genes (p < 10[-16]). The protein interactome of activated bivalent genes revealed the increase of the connectivity of unicellulars and (early) multicellulars, while circadian regulators were depressed. The mutual polyploidy-c-MYC-bivalent genes-associated protein network was organized by gene-hubs engaged in both embryonic development and metastatic cancer including driver (proto)-oncogenes of viral origin. Our data suggest that, in cancer, the atavistic shift goes hand-in-hand with polyploidy and is driven by epigenetic mechanisms impinging on development-related bivalent genes.}, } @article {pmid33211684, year = {2020}, author = {Aubier, TG and Galipaud, M and Erten, EY and Kokko, H}, title = {Transmissible cancers and the evolution of sex under the Red Queen hypothesis.}, journal = {PLoS biology}, volume = {18}, number = {11}, pages = {e3000916}, pmid = {33211684}, issn = {1545-7885}, support = {U54 CA217376/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; Genetics, Population/methods ; Host-Parasite Interactions/genetics ; Humans ; Models, Biological ; Models, Genetic ; Neoplasms/etiology/genetics ; Parasites ; Reproduction/*genetics/physiology ; Selection, Genetic/genetics/*physiology ; Sex ; }, abstract = {The predominance of sexual reproduction in eukaryotes remains paradoxical in evolutionary theory. Of the hypotheses proposed to resolve this paradox, the 'Red Queen hypothesis' emphasises the potential of antagonistic interactions to cause fluctuating selection, which favours the evolution and maintenance of sex. Whereas empirical and theoretical developments have focused on host-parasite interactions, the premises of the Red Queen theory apply equally well to any type of antagonistic interactions. Recently, it has been suggested that early multicellular organisms with basic anticancer defences were presumably plagued by antagonistic interactions with transmissible cancers and that this could have played a pivotal role in the evolution of sex. Here, we dissect this argument using a population genetic model. One fundamental aspect distinguishing transmissible cancers from other parasites is the continual production of cancerous cell lines from hosts' own tissues. We show that this influx dampens fluctuating selection and therefore makes the evolution of sex more difficult than in standard Red Queen models. Although coevolutionary cycling can remain sufficient to select for sex under some parameter regions of our model, we show that the size of those regions shrinks once we account for epidemiological constraints. Altogether, our results suggest that horizontal transmission of cancerous cells is unlikely to cause fluctuating selection favouring sexual reproduction. Nonetheless, we confirm that vertical transmission of cancerous cells can promote the evolution of sex through a separate mechanism, known as similarity selection, that does not depend on coevolutionary fluctuations.}, } @article {pmid33184914, year = {2021}, author = {Castillo, SP and Keymer, JE and Marquet, PA}, title = {Do microenvironmental changes disrupt multicellular organisation with ageing, enacting and favouring the cancer cell phenotype?.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {43}, number = {2}, pages = {e2000126}, doi = {10.1002/bies.202000126}, pmid = {33184914}, issn = {1521-1878}, mesh = {Aging ; Animals ; *Biological Evolution ; Ecosystem ; Humans ; *Neoplasms/genetics ; Phenotype ; }, abstract = {Cancer is a singular cellular state, the emergence of which destabilises the homeostasis reached through the evolution to multicellularity. We present the idea that the onset of the cellular disobedience to the metazoan functional and structural architecture, known as the cancer phenotype, is triggered by changes in the cell's external environment that occur with ageing: what ensues is a breach of the social contract of multicellular life characteristic of metazoans. By integrating old ideas with new evidence, we propose that with ageing the environmental information that maintains a multicellular organisation is eroded, rewiring internal processes of the cell, and resulting in an internal shift towards an ancestral condition resulting in the pseudo-multicellular cancer phenotype. Once that phenotype emerges, a new local social contract is built, different from the homeostatic one, leading to tumour formation and the foundation of a novel local ecosystem.}, } @article {pmid33180181, year = {2020}, author = {Konarska, A and Łotocka, B}, title = {Glandular trichomes of Robinia viscosa Vent. var. hartwigii (Koehne) Ashe (Faboideae, Fabaceae)-morphology, histochemistry and ultrastructure.}, journal = {Planta}, volume = {252}, number = {6}, pages = {102}, pmid = {33180181}, issn = {1432-2048}, mesh = {Flowers ; *Histocytochemistry ; Microscopy, Electron ; Plant Leaves ; *Robinia/chemistry/ultrastructure ; *Trichomes/chemistry/ultrastructure ; }, abstract = {Permanent glandular trichomes of Robinia viscosa var. hartwigii produce viscous secretion containing several secondary metabolites, as lipids, mucilage, flavonoids, proteins and alkaloids. Robinia viscosa var. hartwigii (Hartweg's locust) is an ornamental tree with high apicultural value. It can be planted in urban greenery and in degraded areas. The shoots, leaves, and inflorescences of this plant are equipped with numerous persistent glandular trichomes producing sticky secretion. The distribution, origin, development, morphology, anatomy, and ultrastructure of glandular trichomes of Hartweg's locust flowers as well as the localisation and composition of their secretory products were investigated for the first time. To this end, light, scanning, and transmission electron microscopy combined with histochemical and fluorescence techniques were used. The massive glandular trichomes differing in the distribution, length, and stage of development were built of a multicellular and multiseriate stalk and a multicellular head. The secretory cells in the stalk and head had large nuclei with nucleoli, numerous chloroplasts with thylakoids and starch grains, mitochondria, endoplasmic reticulum profiles, Golgi apparatus, vesicles, and multivesicular bodies. Many vacuoles contained phenolic compounds dissolved or forming various condensed deposits. The secretion components were transported through symplast elements, and the granulocrine and eccrine modes of nectar secretion were observed. The secretion was accumulated in the subcuticular space at the trichome apex and released through a pore in the cuticle. Histochemical and fluorescence assays showed that the trichomes and secretion contained lipophilic and polyphenol compounds, polysaccharides, proteins, and alkaloids. We suggest that these metabolites may serve an important function in protection of plants against biotic stress conditions and may also be a source of phytopharmaceuticals in the future.}, } @article {pmid33177521, year = {2020}, author = {Du, K and Luo, Q and Yin, L and Wu, J and Liu, Y and Gan, J and Dong, A and Shen, WH}, title = {OsChz1 acts as a histone chaperone in modulating chromatin organization and genome function in rice.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {5717}, pmid = {33177521}, issn = {2041-1723}, mesh = {CRISPR-Cas Systems ; Chromatin/genetics/*metabolism ; DNA Methylation ; Flowers/metabolism ; Gene Expression Regulation, Plant ; Genome, Plant ; Histones/genetics/*metabolism ; Molecular Chaperones/genetics/metabolism ; Mutation ; Nucleosomes/genetics ; Oryza/*genetics/growth & development/metabolism ; Phylogeny ; Plant Proteins/genetics/*metabolism ; Plants, Genetically Modified ; Protein Multimerization ; }, abstract = {While the yeast Chz1 acts as a specific histone-chaperone for H2A.Z, functions of CHZ-domain proteins in multicellular eukaryotes remain obscure. Here, we report on the functional characterization of OsChz1, a sole CHZ-domain protein identified in rice. OsChz1 interacts with both the canonical H2A-H2B dimer and the variant H2A.Z-H2B dimer. Within crystal structure the C-terminal region of OsChz1 binds H2A-H2B via an acidic region, pointing to a previously unknown recognition mechanism. Knockout of OsChz1 leads to multiple plant developmental defects. At genome-wide level, loss of OsChz1 causes mis-regulations of thousands of genes and broad alterations of nucleosome occupancy as well as reductions of H2A.Z-enrichment. While OsChz1 associates with chromatin regions enriched of repressive histone marks (H3K27me3 and H3K4me2), its loss does not affect the genome landscape of DNA methylation. Taken together, it is emerging that OsChz1 functions as an important H2A/H2A.Z-H2B chaperone in dynamic regulation of chromatin for higher eukaryote development.}, } @article {pmid33169570, year = {2020}, author = {Ma, X and Li, K and Wang, Z and Wei, D and Tang, Q}, title = {[Research progress in regulation model in different types of plant trichome].}, journal = {Sheng wu gong cheng xue bao = Chinese journal of biotechnology}, volume = {36}, number = {10}, pages = {2051-2065}, doi = {10.13345/j.cjb.200114}, pmid = {33169570}, issn = {1872-2075}, mesh = {Arabidopsis/genetics ; *Gene Expression Regulation, Plant ; Gossypium/genetics ; Solanum lycopersicum ; Plant Growth Regulators/genetics/metabolism ; *Trichomes/genetics ; }, abstract = {Plant trichomes are special structures that originate from epidermal outgrowths. Trichomes play an important role in plant defense against pests and diseases, and possess economic and medicinal values. Study on molecular mechanism of plant trichomes will contribute to the molecular design breeding and genetic improvement of crops. In recent years, the regulation mechanism of trichome development has been basically clarified in the model plant Arabidopsis thaliana, while great progresses are also found in other plant species. In this review, we focus on the developmental regulation of trichome formation from gene and phytohormones levels in Arabidopsis and cotton (with unicellular trichomes), as well as in tomato and Artemisia annua (with multicellular trichomes). The research progress associated with trichomes is also introduced in other typical monocotyledons and dicotyledons. Finally, the research and application of plant trichomes are prospected.}, } @article {pmid33165962, year = {2021}, author = {Blackstone, NW and Gutterman, JU}, title = {Can natural selection and druggable targets synergize? Of nutrient scarcity, cancer, and the evolution of cooperation.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {43}, number = {2}, pages = {e2000160}, doi = {10.1002/bies.202000160}, pmid = {33165962}, issn = {1521-1878}, mesh = {Animals ; *Biological Evolution ; Humans ; *Neoplasms/drug therapy ; Nutrients ; Selection, Genetic ; Symbiosis ; }, abstract = {Since the dawn of molecular biology, cancer therapy has focused on druggable targets. Despite some remarkable successes, cell-level evolution remains a potent antagonist to this approach. We suggest that a deeper understanding of the breakdown of cooperation can synergize the evolutionary and druggable-targets approaches. Complexity requires cooperation, whether between cells of different species (symbiosis) or between cells of the same organism (multicellularity). Both forms of cooperation may be associated with nutrient scarcity, which in turn may be associated with a chemiosmotic metabolism. A variety of examples from modern organisms supports these generalities. Indeed, mammalian cancers-unicellular, glycolytic, and fast-replicating-parallel these examples. Nutrient scarcity, chemiosmosis, and associated signaling may favor cooperation, while under conditions of nutrient abundance a fermentative metabolism may signal the breakdown of cooperation. Manipulating this metabolic milieu may potentiate the effects of targeted therapeutics. Specific opportunities are discussed in this regard, including avicins, a novel plant product.}, } @article {pmid33159138, year = {2020}, author = {Willman, S and Peel, JS and Ineson, JR and Schovsbo, NH and Rugen, EJ and Frei, R}, title = {Ediacaran Doushantuo-type biota discovered in Laurentia.}, journal = {Communications biology}, volume = {3}, number = {1}, pages = {647}, pmid = {33159138}, issn = {2399-3642}, mesh = {Animals ; *Biological Evolution ; *Biota ; *Fossils ; Geologic Sediments ; Greenland ; }, abstract = {The Ediacaran period (635-541 Ma) was a time of major environmental change, accompanied by a transition from a microbial world to the animal world we know today. Multicellular, macroscopic organisms preserved as casts and molds in Ediacaran siliciclastic rocks are preserved worldwide and provide snapshots of early organismal, including animal, evolution. Remarkable evolutionary advances are also witnessed by diverse cellular and subcellular phosphatized microfossils described from the Doushantuo Formation in China, the only source showing a diversified assemblage of microfossils. Here, we greatly extend the known distribution of this Doushantuo-type biota in reporting an Ediacaran Lagerstätte from Laurentia (Portfjeld Formation, North Greenland), with phosphatized animal-like eggs, embryos, acritarchs, and cyanobacteria, the age of which is constrained by the Shuram-Wonoka anomaly (c. 570-560 Ma). The discovery of these Ediacaran phosphatized microfossils from outside East Asia extends the distribution of the remarkable biota to a second palaeocontinent in the other hemisphere of the Ediacaran world, considerably expanding our understanding of the temporal and environmental distribution of organisms immediately prior to the Cambrian explosion.}, } @article {pmid33148926, year = {2020}, author = {Katoh, T and Satoh, M}, title = {[Environment and immunity-Allergies and autoimmune diseases from epidemiological perspective].}, journal = {Nihon eiseigaku zasshi. Japanese journal of hygiene}, volume = {75}, number = {0}, pages = {}, doi = {10.1265/jjh.20005}, pmid = {33148926}, issn = {1882-6482}, mesh = {Adolescent ; Adult ; Aged ; Autoantibodies ; Autoimmune Diseases/epidemiology/*immunology ; *Autoimmunity ; Biological Evolution ; Celiac Disease/immunology ; Child ; Child, Preschool ; Environment ; Female ; Humans ; Hypersensitivity/epidemiology/*immunology ; Infant ; Male ; Middle Aged ; Young Adult ; }, abstract = {Immunity, which denotes the protection of multicellular organisms against various bacterial and viral infections, is an essential protective mechanism for living organisms. Allergy is a reaction to a foreign substance existing in the environment that is basically not a component of the self. Additionally, autoimmune diseases are associated with the dysfunction in the recognition of self and non-self, and are pathological conditions caused by immune cells attacking their own tissues and cells. In this paper, we outline the current status of immunity with respect to the environment from the epidemiological perspective with regard to the following: (1) evolution and immunity, (2) allergy, (3) autoantibodies, (4) autoimmune diseases, (5) relationships of immunity with the environment, allergy, autoantibodies, and autoimmune diseases, and (6) celiac disease.}, } @article {pmid33143227, year = {2020}, author = {Petrushin, I and Belikov, S and Chernogor, L}, title = {Cooperative Interaction of Janthinobacterium sp. SLB01 and Flavobacterium sp. SLB02 in the Diseased Sponge Lubomirskia baicalensis.}, journal = {International journal of molecular sciences}, volume = {21}, number = {21}, pages = {}, pmid = {33143227}, issn = {1422-0067}, mesh = {Animals ; Cooperative Behavior ; *Ecosystem ; Flavobacterium/*physiology ; Lakes ; Oxalobacteraceae/*physiology ; Phylogeny ; Porifera/*metabolism/*microbiology ; *Symbiosis ; }, abstract = {Endemic freshwater sponges (demosponges, Lubomirskiidae) dominate in Lake Baikal, Central Siberia, Russia. These sponges are multicellular filter-feeding animals that represent a complex consortium of many species of eukaryotes and prokaryotes. In recent years, mass disease and death of Lubomirskia baicalensis has been a significant problem in Lake Baikal. The etiology and ecology of these events remain unknown. Bacteria from the families Flavobacteriaceae and Oxalobacteraceae dominate the microbiomes of diseased sponges. Both species are opportunistic pathogens common in freshwater ecosystems. The aim of our study was to analyze the genomes of strains Janthinobacterium sp. SLB01 and Flavobacterium sp. SLB02, isolated from diseased sponges to identify the reasons for their joint dominance. Janthinobacterium sp. SLB01 attacks other cells using a type VI secretion system and suppresses gram-positive bacteria with violacein, and regulates its own activity via quorum sensing. It produces floc and strong biofilm by exopolysaccharide biosynthesis and PEP-CTERM/XrtA protein expression. Flavobacterium sp. SLB02 utilizes the fragments of cell walls produced by polysaccharides. These two strains have a marked difference in carbohydrate acquisition. We described a possible means of joint occupation of the ecological niche in the freshwater sponge microbial community. This study expands the understanding of the symbiotic relationship of microorganisms with freshwater Baikal sponges.}, } @article {pmid33138108, year = {2020}, author = {Ingargiola, C and Turqueto Duarte, G and Robaglia, C and Leprince, AS and Meyer, C}, title = {The Plant Target of Rapamycin: A Conduc TOR of Nutrition and Metabolism in Photosynthetic Organisms.}, journal = {Genes}, volume = {11}, number = {11}, pages = {}, pmid = {33138108}, issn = {2073-4425}, mesh = {Chlorophyta/metabolism ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Metabolic Networks and Pathways ; Models, Biological ; Nitrogen/metabolism ; Phosphates/metabolism ; Photosynthesis ; Plant Development ; Plant Proteins/*metabolism ; Plants/*metabolism ; Potassium/metabolism ; Signal Transduction ; Stress, Physiological ; Sugars/metabolism ; Sulfur/metabolism ; TOR Serine-Threonine Kinases/*metabolism ; }, abstract = {Living organisms possess many mechanisms to sense nutrients and favorable conditions, which allow them to grow and develop. Photosynthetic organisms are very diverse, from green unicellular algae to multicellular flowering plants, but most of them are sessile and thus unable to escape from the biotic and abiotic stresses they experience. The Target of Rapamycin (TOR) signaling pathway is conserved in all eukaryotes and acts as a central regulatory hub between growth and extrinsic factors, such as nutrients or stress. However, relatively little is known about the regulations and roles of this pathway in plants and algae. Although some features of the TOR pathway seem to have been highly conserved throughout evolution, others clearly differ in plants, perhaps reflecting adaptations to different lifestyles and the rewiring of this primordial signaling module to adapt to specific requirements. Indeed, TOR is involved in plant responses to a vast array of signals including nutrients, hormones, light, stresses or pathogens. In this review, we will summarize recent studies that address the regulations of TOR by nutrients in photosynthetic organisms, and the roles of TOR in controlling important metabolic pathways, highlighting similarities and differences with the other eukaryotes.}, } @article {pmid33126770, year = {2020}, author = {Combarnous, Y and Nguyen, TMD}, title = {Cell Communications among Microorganisms, Plants, and Animals: Origin, Evolution, and Interplays.}, journal = {International journal of molecular sciences}, volume = {21}, number = {21}, pages = {}, pmid = {33126770}, issn = {1422-0067}, mesh = {Animals ; Bacteria/*metabolism ; *Biological Evolution ; *Cell Communication ; Fungi/*metabolism ; Phylogeny ; Plants/*metabolism ; Viruses/*metabolism ; }, abstract = {Cellular communications play pivotal roles in multi-cellular species, but they do so also in uni-cellular species. Moreover, cells communicate with each other not only within the same individual, but also with cells in other individuals belonging to the same or other species. These communications occur between two unicellular species, two multicellular species, or between unicellular and multicellular species. The molecular mechanisms involved exhibit diversity and specificity, but they share common basic features, which allow common pathways of communication between different species, often phylogenetically very distant. These interactions are possible by the high degree of conservation of the basic molecular mechanisms of interaction of many ligand-receptor pairs in evolutionary remote species. These inter-species cellular communications played crucial roles during Evolution and must have been positively selected, particularly when collectively beneficial in hostile environments. It is likely that communications between cells did not arise after their emergence, but were part of the very nature of the first cells. Synchronization of populations of non-living protocells through chemical communications may have been a mandatory step towards their emergence as populations of living cells and explain the large commonality of cell communication mechanisms among microorganisms, plants, and animals.}, } @article {pmid33126482, year = {2020}, author = {Kulkarni, P}, title = {Intrinsically Disordered Proteins: Insights from Poincaré, Waddington, and Lamarck.}, journal = {Biomolecules}, volume = {10}, number = {11}, pages = {}, pmid = {33126482}, issn = {2218-273X}, mesh = {*Biological Evolution ; Humans ; Intrinsically Disordered Proteins/chemistry/*genetics ; Phenotype ; *Protein Conformation ; }, abstract = {The past quarter-century may justly be referred to as a period analogous to the "Cambrian explosion" in the history of proteins. This period is marked by the appearance of the intrinsically disordered proteins (IDPs) on the scene since their discovery in the mid-1990s. Here, I first reflect on how we accidentally stumbled on these fascinating molecules. Next, I describe our research on the IDPs over the past decade and identify six areas as important for future research in this field. In addition, I draw on discoveries others in the field have made to present a more comprehensive essay. More specifically, I discuss the role of IDPs in two fundamental aspects of life: in phenotypic switching, and in multicellularity that marks one of the major evolutionary transitions. I highlight how serendipity, imagination, and an interdisciplinary approach embodying empirical evidence and theoretical insights from the works of Poincaré, Waddington, and Lamarck, shaped our thinking, and how this led us to propose the MRK hypothesis, a conceptual framework addressing phenotypic switching, the emergence of new traits, and adaptive evolution via nongenetic and IDP conformation-based mechanisms. Finally, I present a perspective on the evolutionary link between phenotypic switching and the origin of multicellularity.}, } @article {pmid33097400, year = {2021}, author = {Véron, E and Vernoux, T and Coudert, Y}, title = {Phyllotaxis from a Single Apical Cell.}, journal = {Trends in plant science}, volume = {26}, number = {2}, pages = {124-131}, doi = {10.1016/j.tplants.2020.09.014}, pmid = {33097400}, issn = {1878-4372}, mesh = {*Bryopsida ; *Meristem/genetics ; Plant Leaves ; Plant Shoots ; }, abstract = {Phyllotaxis, the geometry of leaf arrangement around stems, determines plant architecture. Molecular interactions coordinating the formation of phyllotactic patterns have mainly been studied in multicellular shoot apical meristems of flowering plants. Phyllotaxis evolved independently in the major land plant lineages. In mosses, it arises from a single apical cell, raising the question of how asymmetric divisions of a single-celled meristem create phyllotactic patterns and whether associated genetic processes are shared across lineages. We present an overview of the mechanisms governing shoot apical cell specification and activity in the model moss, Physcomitrium patens, and argue that similar molecular regulatory modules have been deployed repeatedly across evolution to operate at different scales and drive apical function in convergent shoot forms.}, } @article {pmid33093150, year = {2020}, author = {Soubigou, A and Ross, EG and Touhami, Y and Chrismas, N and Modepalli, V}, title = {Regeneration in the sponge Sycon ciliatum partly mimics postlarval development.}, journal = {Development (Cambridge, England)}, volume = {147}, number = {22}, pages = {}, doi = {10.1242/dev.193714}, pmid = {33093150}, issn = {1477-9129}, mesh = {Animals ; Embryonic Development/*physiology ; Larva ; Porifera/*embryology ; Regeneration/*physiology ; Transcriptome/*physiology ; }, abstract = {Somatic cells dissociated from an adult sponge can reorganize and develop into a juvenile-like sponge, a remarkable phenomenon of regeneration. However, the extent to which regeneration recapitulates embryonic developmental pathways has remained enigmatic. We have standardized and established a sponge Sycon ciliatum regeneration protocol from dissociated cells. Morphological analysis demonstrated that dissociated sponge cells follow a series of morphological events resembling postembryonic development. We performed high-throughput sequencing on regenerating samples and compared the data with that from regular postlarval development. Our comparative transcriptomic analysis revealed that sponge regeneration is as equally dynamic as embryogenesis. We found that sponge regeneration is orchestrated by recruiting pathways similar to those utilized in embryonic development. We also demonstrated that sponge regeneration is accompanied by cell death at early stages, revealing the importance of apoptosis in remodelling the primmorphs to initiate re-development. Because sponges are likely to be the first branch of extant multicellular animals, we suggest that this system can be explored to study the genetic features underlying the evolution of multicellularity and regeneration.}, } @article {pmid33093080, year = {2020}, author = {Hammarlund, EU and Flashman, E and Mohlin, S and Licausi, F}, title = {Oxygen-sensing mechanisms across eukaryotic kingdoms and their roles in complex multicellularity.}, journal = {Science (New York, N.Y.)}, volume = {370}, number = {6515}, pages = {}, doi = {10.1126/science.aba3512}, pmid = {33093080}, issn = {1095-9203}, mesh = {Anaerobiosis ; Animals ; Biological Evolution ; Dioxygenases/genetics/*metabolism ; Eukaryota/*classification/*metabolism ; Fungi ; Oxygen/*metabolism ; Plants ; }, abstract = {Oxygen-sensing mechanisms of eukaryotic multicellular organisms coordinate hypoxic cellular responses in a spatiotemporal manner. Although this capacity partly allows animals and plants to acutely adapt to oxygen deprivation, its functional and historical roots in hypoxia emphasize a broader evolutionary role. For multicellular life-forms that persist in settings with variable oxygen concentrations, the capacity to perceive and modulate responses in and between cells is pivotal. Animals and higher plants represent the most complex life-forms that ever diversified on Earth, and their oxygen-sensing mechanisms demonstrate convergent evolution from a functional perspective. Exploring oxygen-sensing mechanisms across eukaryotic kingdoms can inform us on biological innovations to harness ever-changing oxygen availability at the dawn of complex life and its utilization for their organismal development.}, } @article {pmid33081011, year = {2020}, author = {Steinberg, E and Orehov, N and Tischenko, K and Schwob, O and Zamir, G and Hubert, A and Manevitch, Z and Benny, O}, title = {Rapid Clearing for High Resolution 3D Imaging of Ex Vivo Pancreatic Cancer Spheroids.}, journal = {International journal of molecular sciences}, volume = {21}, number = {20}, pages = {}, pmid = {33081011}, issn = {1422-0067}, mesh = {Cell Line, Tumor ; Extracellular Matrix/metabolism ; Human Umbilical Vein Endothelial Cells/metabolism ; Humans ; *Imaging, Three-Dimensional ; Pancreatic Neoplasms/*diagnostic imaging/*pathology ; Spheroids, Cellular/*pathology ; Tumor Microenvironment ; }, abstract = {The currently accepted imaging methods have been a central hurdle to imaging the finer details of tumor behavior in three-dimensional (3D) ex vivo multicellular culture models. In our search for an improved way of imaging tumor behavior in its physiological-like niche, we developed a simple, efficient, and straightforward procedure using standard reagents and imaging equipment that significantly enhanced 3D imaging up to a ~200-micron depth. We tested its efficacy on pancreatic spheroids, prototypes of high-density tissues that are difficult to image. We found we could both save time with this method and extract information about pancreatic tumor spheroids that previously was difficult to obtain. We were able to discern clear differences in the organization of pancreatic tumor spheroids generated from different origins, suggesting cell-specific, inherent, bottom-up organization with a correlation to the level of malignancy. We also examined the dynamic changes in the spheroids at predetermined time points, providing important information related to tissue morphogenesis and its metabolic state. Lastly, this process enabled us to assess a drug vehicle's potential to penetrate dense tumor tissue by improving our view of the inert particles' diffusion in the 3D spheroid. This clearing method, a simple procedure, can open the door to more accurate imaging and reveal more about cancer behavior.}, } @article {pmid33072737, year = {2020}, author = {Teulière, J and Bernard, G and Bapteste, E}, title = {The Distribution of Genes Associated With Regulated Cell Death Is Decoupled From the Mitochondrial Phenotypes Within Unicellular Eukaryotic Hosts.}, journal = {Frontiers in cell and developmental biology}, volume = {8}, number = {}, pages = {536389}, pmid = {33072737}, issn = {2296-634X}, abstract = {Genetically regulated cell death (RCD) occurs in all domains of life. In eukaryotes, the evolutionary origin of the mitochondrion and of certain forms of RCD, in particular apoptosis, are thought to coincide, suggesting a central general role for mitochondria in cellular suicide. We tested this mitochondrial centrality hypothesis across a dataset of 67 species of protists, presenting 5 classes of mitochondrial phenotypes, including functional mitochondria, metabolically diversified mitochondria, functionally reduced mitochondria (Mitochondrion Related Organelle or MRO) and even complete absence of mitochondria. We investigated the distribution of genes associated with various forms of RCD. No homologs for described mammalian regulators of regulated necrosis could be identified in our set of 67 unicellular taxa. Protists with MRO and the secondarily a mitochondriate Monocercomonoides exilis display heterogeneous reductions of apoptosis gene sets with respect to typical mitochondriate protists. Remarkably, despite the total lack of mitochondria in M. exilis, apoptosis-associated genes could still be identified. These same species of protists with MRO and M. exilis harbored non-reduced autophagic cell death gene sets. Moreover, transiently multicellular protist taxa appeared enriched in apoptotic and autophagy associated genes compared to free-living protists. This analysis suggests that genes associated with apoptosis in animals and the presence of the mitochondria are significant yet non-essential biological components for RCD in protists. More generally, our results support the hypothesis of a selection for RCD, including both apoptosis and autophagy, as a developmental mechanism linked to multicellularity.}, } @article {pmid33068526, year = {2020}, author = {Palazzo, AF and Koonin, EV}, title = {Functional Long Non-coding RNAs Evolve from Junk Transcripts.}, journal = {Cell}, volume = {183}, number = {5}, pages = {1151-1161}, doi = {10.1016/j.cell.2020.09.047}, pmid = {33068526}, issn = {1097-4172}, support = {//CIHR/Canada ; }, mesh = {Animals ; DNA, Intergenic/genetics ; Enhancer Elements, Genetic/genetics ; Evolution, Molecular ; Humans ; RNA, Long Noncoding/*genetics/metabolism ; RNA, Messenger/*genetics/metabolism ; Transcription, Genetic ; }, abstract = {Transcriptome studies reveal pervasive transcription of complex genomes, such as those of mammals. Despite popular arguments for functionality of most, if not all, of these transcripts, genome-wide analysis of selective constraints indicates that most of the produced RNA are junk. However, junk is not garbage. On the contrary, junk transcripts provide the raw material for the evolution of diverse long non-coding (lnc) RNAs by non-adaptive mechanisms, such as constructive neutral evolution. The generation of many novel functional entities, such as lncRNAs, that fuels organismal complexity does not seem to be driven by strong positive selection. Rather, the weak selection regime that dominates the evolution of most multicellular eukaryotes provides ample material for functional innovation with relatively little adaptation involved.}, } @article {pmid33064719, year = {2020}, author = {Liu, XB and Xia, EH and Li, M and Cui, YY and Wang, PM and Zhang, JX and Xie, BG and Xu, JP and Yan, JJ and Li, J and Nagy, LG and Yang, ZL}, title = {Transcriptome data reveal conserved patterns of fruiting body development and response to heat stress in the mushroom-forming fungus Flammulina filiformis.}, journal = {PloS one}, volume = {15}, number = {10}, pages = {e0239890}, pmid = {33064719}, issn = {1932-6203}, mesh = {Agaricales/*genetics/growth & development/metabolism ; Conserved Sequence ; *Evolution, Molecular ; Fruiting Bodies, Fungal/genetics/*growth & development/metabolism ; Fungal Proteins/genetics/metabolism ; Heat-Shock Proteins/genetics/metabolism ; *Heat-Shock Response ; *Transcriptome ; }, abstract = {Mushroom-forming fungi are complex multicellular organisms that form the basis of a large industry, yet, our understanding of the mechanisms of mushroom development and its responses to various stresses remains limited. The winter mushroom (Flammulina filiformis) is cultivated at a large commercial scale in East Asia and is a species with a preference for low temperatures. This study investigated fruiting body development in F. filiformis by comparing transcriptomes of 4 developmental stages, and compared the developmental genes to a 200-genome dataset to identify conserved genes involved in fruiting body development, and examined the response of heat sensitive and -resistant strains to heat stress. Our data revealed widely conserved genes involved in primordium development of F. filiformis, many of which originated before the emergence of the Agaricomycetes, indicating co-option for complex multicellularity during evolution. We also revealed several notable fruiting-specific genes, including the genes with conserved stipe-specific expression patterns and the others which related to sexual development, water absorption, basidium formation and sporulation, among others. Comparative analysis revealed that heat stress induced more genes in the heat resistant strain (M1) than in the heat sensitive one (XR). Of particular importance are the hsp70, hsp90 and fes1 genes, which may facilitate the adjustment to heat stress in the early stages of fruiting body development. These data highlighted novel genes involved in complex multicellular development in fungi and aid further studies on gene function and efforts to improve the productivity and heat tolerance in mushroom-forming fungi.}, } @article {pmid33062243, year = {2020}, author = {Arias Del Angel, JA and Nanjundiah, V and Benítez, M and Newman, SA}, title = {Interplay of mesoscale physics and agent-like behaviors in the parallel evolution of aggregative multicellularity.}, journal = {EvoDevo}, volume = {11}, number = {}, pages = {21}, pmid = {33062243}, issn = {2041-9139}, abstract = {Myxobacteria and dictyostelids are prokaryotic and eukaryotic multicellular lineages, respectively, that after nutrient depletion aggregate and develop into structures called fruiting bodies. The developmental processes and resulting morphological outcomes resemble one another to a remarkable extent despite their independent origins, the evolutionary distance between them and the lack of traceable homology in molecular mechanisms. We hypothesize that the morphological parallelism between the two lineages arises as the consequence of the interplay within multicellular aggregates between generic processes, physical and physicochemical processes operating similarly in living and non-living matter at the mesoscale (~10[-3]-10[-1] m) and agent-like behaviors, unique to living systems and characteristic of the constituent cells, considered as autonomous entities acting according to internal rules in a shared environment. Here, we analyze the contributions of generic and agent-like determinants in myxobacteria and dictyostelid development and their roles in the generation of their common traits. Consequent to aggregation, collective cell-cell contacts mediate the emergence of liquid-like properties, making nascent multicellular masses subject to novel patterning and morphogenetic processes. In both lineages, this leads to behaviors such as streaming, rippling, and rounding-up, as seen in non-living fluids. Later the aggregates solidify, leading them to exhibit additional generic properties and motifs. Computational models suggest that the morphological phenotypes of the multicellular masses deviate from the predictions of generic physics due to the contribution of agent-like behaviors of cells such as directed migration, quiescence, and oscillatory signal transduction mediated by responses to external cues. These employ signaling mechanisms that reflect the evolutionary histories of the respective organisms. We propose that the similar developmental trajectories of myxobacteria and dictyostelids are more due to shared generic physical processes in coordination with analogous agent-type behaviors than to convergent evolution under parallel selection regimes. Insights from the biology of these aggregative forms may enable a unified understanding of developmental evolution, including that of animals and plants.}, } @article {pmid33060357, year = {2020}, author = {Toda, S and McKeithan, WL and Hakkinen, TJ and Lopez, P and Klein, OD and Lim, WA}, title = {Engineering synthetic morphogen systems that can program multicellular patterning.}, journal = {Science (New York, N.Y.)}, volume = {370}, number = {6514}, pages = {327-331}, pmid = {33060357}, issn = {1095-9203}, support = {F32 DK123939/DK/NIDDK NIH HHS/United States ; R01 DE028496/DE/NIDCR NIH HHS/United States ; R35 DE026602/DE/NIDCR NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; *Body Patterning ; Drosophila melanogaster/growth & development ; Fibroblasts ; Green Fluorescent Proteins/genetics/*metabolism ; Protein Engineering ; Receptors, Notch/genetics/metabolism ; Tissue Engineering/*methods ; }, abstract = {In metazoan tissues, cells decide their fates by sensing positional information provided by specialized morphogen proteins. To explore what features are sufficient for positional encoding, we asked whether arbitrary molecules (e.g., green fluorescent protein or mCherry) could be converted into synthetic morphogens. Synthetic morphogens expressed from a localized source formed a gradient when trapped by surface-anchoring proteins, and they could be sensed by synthetic receptors. Despite their simplicity, these morphogen systems yielded patterns reminiscent of those observed in vivo. Gradients could be reshaped by altering anchor density or by providing a source of competing inhibitor. Gradient interpretation could be altered by adding feedback loops or morphogen cascades to receiver cell response circuits. Orthogonal cell-cell communication systems provide insight into morphogen evolution and a platform for engineering tissues.}, } @article {pmid33058872, year = {2020}, author = {Dyrka, W and Coustou, V and Daskalov, A and Lends, A and Bardin, T and Berbon, M and Kauffmann, B and Blancard, C and Salin, B and Loquet, A and Saupe, SJ}, title = {Identification of NLR-associated Amyloid Signaling Motifs in Bacterial Genomes.}, journal = {Journal of molecular biology}, volume = {432}, number = {23}, pages = {6005-6027}, doi = {10.1016/j.jmb.2020.10.004}, pmid = {33058872}, issn = {1089-8638}, mesh = {Amino Acid Motifs/genetics ; Amino Acid Sequence/genetics ; Amyloid/*genetics ; Amyloidogenic Proteins/genetics ; Animals ; Cyanobacteria/genetics ; Drosophila/genetics ; *Evolution, Molecular ; Fungi/genetics ; Genome, Bacterial/genetics ; Immunity, Innate/*genetics ; NLR Proteins/*genetics ; Prions/genetics ; Signal Transduction/genetics ; }, abstract = {In filamentous fungi, amyloid signaling sequences allow Nod-like receptors (NLRs) to activate downstream cell-death inducing proteins with HeLo and HeLo-like (HELL) domains and amyloid RHIM and RHIM-related motifs control immune defense pathways in mammals and flies. Herein, we show bioinformatically that analogous amyloid signaling motifs exist in bacteria. These short motifs are found at the N terminus of NLRs and at the C terminus of proteins with a domain we term BELL. The corresponding NLR and BELL proteins are encoded by adjacent genes. We identify 10 families of such bacterial amyloid signaling sequences (BASS), one of which (BASS3) is homologous to RHIM and a fungal amyloid motif termed PP. BASS motifs occur nearly exclusively in bacteria forming multicellular structures (mainly in Actinobacteria and Cyanobacteria). We analyze experimentally a subset of seven of these motifs (from the most common BASS1 family and the RHIM-related BASS3 family) and find that these sequences form fibrils in vitro. Using a fungal in vivo model, we show that all tested BASS-motifs form prions and that the NLR-side motifs seed prion-formation of the corresponding BELL-side motif. We find that BASS3 motifs show partial prion cross-seeding with mammalian RHIM and fungal PP-motifs and that proline mutations on key positions of the BASS3 core motif, conserved in RHIM and PP-motifs, abolish prion formation. This work expands the paradigm of prion amyloid signaling to multicellular prokaryotes and suggests a long-term evolutionary conservation of these motifs from bacteria, to fungi and animals.}, } @article {pmid33050851, year = {2020}, author = {Kurakin, GF and Samoukina, AM and Potapova, NA}, title = {Bacterial and Protozoan Lipoxygenases Could be Involved in Cell-to-Cell Signaling and Immune Response Suppression.}, journal = {Biochemistry. Biokhimiia}, volume = {85}, number = {9}, pages = {1048-1071}, doi = {10.1134/S0006297920090059}, pmid = {33050851}, issn = {1608-3040}, mesh = {Animals ; Bacteria/*enzymology ; *Biological Evolution ; *Cell Communication ; Humans ; Immunity/*immunology ; Lipoxygenases/*metabolism ; Protozoan Proteins/*metabolism ; }, abstract = {Lipoxygenases are found in animals, plants, and fungi, where they are involved in a wide range of cell-to-cell signaling processes. The presence of lipoxygenases in a number of bacteria and protozoa has been also established, but their biological significance remains poorly understood. Several hypothetical functions of lipoxygenases in bacteria and protozoa have been suggested without experimental validation. The objective of our study was evaluating the functions of bacterial and protozoan lipoxygenases by evolutionary and taxonomic analysis using bioinformatics tools. Lipoxygenase sequences were identified and examined using BLAST, followed by analysis of constructed phylogenetic trees and networks. Our results support the theory on the involvement of lipoxygenases in the formation of multicellular structures by microorganisms and their possible evolutionary significance in the emergence of multicellularity. Furthermore, we observed association of lipoxygenases with the suppression of host immune response by parasitic and symbiotic bacteria including dangerous opportunistic pathogens.}, } @article {pmid33035180, year = {2020}, author = {Essen, LO and Vogt, MS and Mösch, HU}, title = {Diversity of GPI-anchored fungal adhesins.}, journal = {Biological chemistry}, volume = {401}, number = {12}, pages = {1389-1405}, doi = {10.1515/hsz-2020-0199}, pmid = {33035180}, issn = {1437-4315}, mesh = {Cell Adhesion ; Glycosylphosphatidylinositols/*metabolism ; Saccharomyces cerevisiae/cytology/*metabolism ; Saccharomyces cerevisiae Proteins/*metabolism ; }, abstract = {Selective adhesion of fungal cells to one another and to foreign surfaces is fundamental for the development of multicellular growth forms and the successful colonization of substrates and host organisms. Accordingly, fungi possess diverse cell wall-associated adhesins, mostly large glycoproteins, which present N-terminal adhesion domains at the cell surface for ligand recognition and binding. In order to function as robust adhesins, these glycoproteins must be covalently linkedto the cell wall via C-terminal glycosylphosphatidylinositol (GPI) anchors by transglycosylation. In this review, we summarize the current knowledge on the structural and functional diversity of so far characterized protein families of adhesion domains and set it into a broad context by an in-depth bioinformatics analysis using sequence similarity networks. In addition, we discuss possible mechanisms for the membrane-to-cell wall transfer of fungal adhesins by membrane-anchored Dfg5 transglycosidases.}, } @article {pmid33031891, year = {2021}, author = {Gao, JG}, title = {Tracking the evolutionary innovations of plant terrestrialization.}, journal = {Gene}, volume = {769}, number = {}, pages = {145203}, doi = {10.1016/j.gene.2020.145203}, pmid = {33031891}, issn = {1879-0038}, mesh = {*Biological Evolution ; Bryophyta/genetics/physiology ; Gene Transfer, Horizontal ; Genome, Plant ; *Plant Physiological Phenomena ; Plants/genetics ; }, abstract = {The gradual transition of the algal ancestor from the freshwater to land has always attracted evolutionary biologists. The recent report of high-quality reference genomes of five Charophyta algae (Spirogloea muscicola, Mesotaenium endlicherianum, Mesostigma viride, Chlorokybus atmophyticus and Penium margaritaceum) and one hornwort (Anthoceros angustus) species sheds light on this fascinating transition. These early diverging plants and algae could have gained new genes from soil bacteria and fungi through horizontal gene transfer (HGT), which was so common during plant terrestrialization and may outrun our expectations. Through reviewing and critical thinking about the advancements on these plant genomes, here, I propose three prospective research directions that need to address in the future: (i) due to the ubiquitous nature of viruses that is similar to soil bacteria and fungi, there is less attention to viruses that probably also play an important role in the genome evolution of plants via HGT; (ii) multicellularity has occurred many times independently, but we still know a little about the biological and ecological mechanisms leading to multi-cellularity in Streptophyta; (iii) and most importantly, the quantitative relationships between genetic innovations and environmental variables such as temperature, precipitation and solar radiation, need pioneering research collaborated by biological evolutionists, computer scientists, and ecologists, which are crucial for understanding the macroevolution of plants and could also be used to simulate the evolution of plants under future climate change.}, } @article {pmid33028229, year = {2020}, author = {Jiang, L and Lu, Y and Zheng, L and Li, G and Chen, L and Zhang, M and Ni, J and Liu, Q and Zhang, Y}, title = {The algal selenoproteomes.}, journal = {BMC genomics}, volume = {21}, number = {1}, pages = {699}, pmid = {33028229}, issn = {1471-2164}, mesh = {Codon, Terminator ; *Eukaryota/genetics/metabolism ; Evolution, Molecular ; Proteome ; *Selenium ; Selenocysteine ; *Selenoproteins/genetics/metabolism ; }, abstract = {BACKGROUND: Selenium is an essential trace element, and selenocysteine (Sec, U) is its predominant form in vivo. Proteins that contain Sec are selenoproteins, whose special structural features include not only the TGA codon encoding Sec but also the SECIS element in mRNA and the conservation of the Sec-flanking region. These unique features have led to the development of a series of bioinformatics methods to predict and research selenoprotein genes. There have been some studies and reports on the evolution and distribution of selenoprotein genes in prokaryotes and multicellular eukaryotes, but the systematic analysis of single-cell eukaryotes, especially algae, has been very limited.

RESULTS: In this study, we predicted selenoprotein genes in 137 species of algae by using a program we previously developed. More than 1000 selenoprotein genes were obtained. A database website was built to record these algae selenoprotein genes (www.selenoprotein.com). These genes belong to 42 selenoprotein families, including three novel selenoprotein gene families.

CONCLUSIONS: This study reveals the primordial state of the eukaryotic selenoproteome. It is an important clue to explore the significance of selenium for primordial eukaryotes and to determine the complete evolutionary spectrum of selenoproteins in all life forms.}, } @article {pmid33024265, year = {2021}, author = {Ibrahim-Hashim, A and Luddy, K and Abrahams, D and Enriquez-Navas, P and Damgaci, S and Yao, J and Chen, T and Bui, MM and Gillies, RJ and O'Farrelly, C and Richards, CL and Brown, JS and Gatenby, RA}, title = {Artificial selection for host resistance to tumour growth and subsequent cancer cell adaptations: an evolutionary arms race.}, journal = {British journal of cancer}, volume = {124}, number = {2}, pages = {455-465}, pmid = {33024265}, issn = {1532-1827}, support = {P30 CA076292/CA/NCI NIH HHS/United States ; U54 CA143970/CA/NCI NIH HHS/United States ; R01 CA077575/CA/NCI NIH HHS/United States ; }, mesh = {Adaptation, Physiological/*physiology ; Animals ; *Biological Evolution ; *Carcinoma, Lewis Lung ; Cell Plasticity/*physiology ; Disease Resistance/*physiology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, SCID ; }, abstract = {BACKGROUND: Cancer progression is governed by evolutionary dynamics in both the tumour population and its host. Since cancers die with the host, each new population of cancer cells must reinvent strategies to overcome the host's heritable defences. In contrast, host species evolve defence strategies over generations if tumour development limits procreation.

METHODS: We investigate this "evolutionary arms race" through intentional breeding of immunodeficient SCID and immunocompetent Black/6 mice to evolve increased tumour suppression. Over 10 generations, we injected Lewis lung mouse carcinoma cells [LL/2-Luc-M38] and selectively bred the two individuals with the slowest tumour growth at day 11. Their male progeny were hosts in the subsequent round.

RESULTS: The evolved SCID mice suppressed tumour growth through biomechanical restriction from increased mesenchymal proliferation, and the evolved Black/6 mice suppressed tumour growth by increasing immune-mediated killing of cancer cells. However, transcriptomic changes of multicellular tissue organisation and function genes allowed LL/2-Luc-M38 cells to adapt through increased matrix remodelling in SCID mice, and reduced angiogenesis, increased energy utilisation and accelerated proliferation in Black/6 mice.

CONCLUSION: Host species can rapidly evolve both immunologic and non-immunologic tumour defences. However, cancer cell plasticity allows effective phenotypic and population-based counter strategies.}, } @article {pmid33009502, year = {2020}, author = {Rochman, ND and Wolf, YI and Koonin, EV}, title = {Deep phylogeny of cancer drivers and compensatory mutations.}, journal = {Communications biology}, volume = {3}, number = {1}, pages = {551}, pmid = {33009502}, issn = {2399-3642}, mesh = {Animals ; Evolution, Molecular ; Genes, Neoplasm/*genetics ; Genes, Tumor Suppressor ; Humans ; Mutation/*genetics ; Neoplasms/*genetics ; Oncogenes/genetics ; Phylogeny ; Sequence Alignment ; }, abstract = {Driver mutations (DM) are the genetic impetus for most cancers. The DM are assumed to be deleterious in species evolution, being eliminated by purifying selection unless compensated by other mutations. We present deep phylogenies for 84 cancer driver genes and investigate the prevalence of 434 DM across gene-species trees. The DM are rare in species evolution, and 181 are completely absent, validating their negative fitness effect. The DM are more common in unicellular than in multicellular eukaryotes, suggesting a link between these mutations and cell proliferation control. 18 DM appear as the ancestral state in one or more major clades, including 3 among mammals. We identify within-gene, compensatory mutations for 98 DM and infer likely interactions between the DM and compensatory sites in protein structures. These findings elucidate the evolutionary status of DM and are expected to advance the understanding of the functions and evolution of oncogenes and tumor suppressors.}, } @article {pmid32991271, year = {2020}, author = {Michalakis, Y and Blanc, S}, title = {The Curious Strategy of Multipartite Viruses.}, journal = {Annual review of virology}, volume = {7}, number = {1}, pages = {203-218}, doi = {10.1146/annurev-virology-010220-063346}, pmid = {32991271}, issn = {2327-0578}, mesh = {DNA Viruses/genetics ; *Genome, Viral ; Humans ; Virion/genetics ; Virus Replication ; Viruses/*genetics ; }, abstract = {Multipartite virus genomes are composed of several segments, each packaged in a distinct viral particle. Although this puzzling genome architecture is found in ∼17% of known viral species, its distribution among hosts or among distinct types of genome-composing nucleic acid remains poorly understood. No convincing advantage of multipartitism has been identified, yet the maintenance of genomic integrity appears problematic. Here we review recent studies shedding light on these issues. Multipartite viruses rapidly modify the copy number of each segment/gene from one host species to another, a putative benefit if host switches are common. One multipartite virus functions in a multicellular way: The segments do not all need to be present in the same cell and can functionally complement across cells, maintaining genome integrity within hosts. The genomic integrity maintenance during host-to-host transmission needs further elucidation. These features challenge several virology foundations and could apply to other multicomponent viral systems.}, } @article {pmid32973760, year = {2020}, author = {Petre, B}, title = {Toward the Discovery of Host-Defense Peptides in Plants.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {1825}, pmid = {32973760}, issn = {1664-3224}, mesh = {Antimicrobial Cationic Peptides/*metabolism ; Bacterial Infections/immunology/*metabolism/microbiology ; Botany ; Host-Pathogen Interactions ; *Plant Diseases/immunology/microbiology/virology ; Plant Immunity ; Plant Proteins/*metabolism ; Plants/immunology/*metabolism/microbiology/virology ; Research ; Signal Transduction ; Virus Diseases/immunology/*metabolism/virology ; }, abstract = {Defense peptides protect multicellular eukaryotes from infections. In biomedical sciences, a dominant conceptual framework refers to defense peptides as host-defense peptides (HDPs), which are bifunctional peptides with both direct antimicrobial and immunomodulatory activities. No HDP has been reported in plants so far, and the very concept of HDP has not been captured yet by the plant science community. Plant science thus lacks the conceptual framework that would coordinate research efforts aimed at discovering plant HDPs. In this perspective article, I used bibliometric and literature survey approaches to raise awareness about the HDP concept among plant scientists, and to encourage research efforts aimed at discovering plant HDPs. Such discovery would enrich our comprehension of the function and evolution of the plant immune system, and provide us with novel molecular tools to develop innovative strategies to control crop diseases.}, } @article {pmid32934242, year = {2020}, author = {Kinsella, CM and Bart, A and Deijs, M and Broekhuizen, P and Kaczorowska, J and Jebbink, MF and van Gool, T and Cotten, M and van der Hoek, L}, title = {Entamoeba and Giardia parasites implicated as hosts of CRESS viruses.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {4620}, pmid = {32934242}, issn = {2041-1723}, mesh = {Adult ; Cohort Studies ; Entamoeba/*virology ; Feces/parasitology/virology ; Female ; Genome, Viral ; Giardia/*virology ; Host Specificity ; Humans ; Male ; Middle Aged ; Phylogeny ; Virus Physiological Phenomena ; Viruses/classification/genetics ; Young Adult ; }, abstract = {Metagenomic techniques have enabled genome sequencing of unknown viruses without isolation in cell culture, but information on the virus host is often lacking, preventing viral characterisation. High-throughput methods capable of identifying virus hosts based on genomic data alone would aid evaluation of their medical or biological relevance. Here, we address this by linking metagenomic discovery of three virus families in human stool samples with determination of probable hosts. Recombination between viruses provides evidence of a shared host, in which genetic exchange occurs. We utilise networks of viral recombination to delimit virus-host clusters, which are then anchored to specific hosts using (1) statistical association to a host organism in clinical samples, (2) endogenous viral elements in host genomes, and (3) evidence of host small RNA responses to these elements. This analysis suggests two CRESS virus families (Naryaviridae and Nenyaviridae) infect Entamoeba parasites, while a third (Vilyaviridae) infects Giardia duodenalis. The trio supplements five CRESS virus families already known to infect eukaryotes, extending the CRESS virus host range to protozoa. Phylogenetic analysis implies CRESS viruses infecting multicellular life have evolved independently on at least three occasions.}, } @article {pmid32931463, year = {2020}, author = {Cai, Y and Huang, J and Xu, H and Zhang, T and Cao, C and Pan, Y}, title = {Synthesis, characterization and application of magnetoferritin nanoparticle by using human H chain ferritin expressed by Pichia pastoris.}, journal = {Nanotechnology}, volume = {31}, number = {48}, pages = {485709}, doi = {10.1088/1361-6528/abb15d}, pmid = {32931463}, issn = {1361-6528}, mesh = {Animals ; Apoferritins/*analysis/genetics/toxicity/ultrastructure ; Fluorescent Dyes/*analysis/toxicity ; Gene Expression ; Humans ; Iron/*analysis/toxicity ; Nanoparticles/*analysis/ultrastructure ; Optical Imaging/*methods ; Oxides/*analysis/toxicity ; Rats, Sprague-Dawley ; Recombinant Proteins/analysis/genetics/toxicity/ultrastructure ; Saccharomycetales/genetics ; }, abstract = {Protein-based nanoparticles have developed rapidly in areas such as drug delivery, biomedical imaging and biocatalysis. Ferritin possesses unique properties that make it attractive as a potential platform for a variety of nanobiotechnological applications. Here we synthesized magnetoferritin (P-MHFn) nanoparticles for the first time by using the human H chain of ferritin that was expressed by Pichia pastoris (P-HFn). Western blot results showed that recombinant P-HFn was successfully expressed after methanol induction. Transmission electron microscopy (TEM) showed the spherical cage-like shape and monodispersion of P-HFn. The synthesized magnetoferritin (P-MHFn) retained the properties of magnetoferritin nanoparticles synthesized using HFn expressed by E. coli (E-MHFn): superparamagnetism under ambient conditions and peroxidase-like activity. It is stable under a wider range of pH values (from 5.0 to 11.0), likely due to post-translational modifications such as N-glycosylation on P-HFn. In vivo near-infrared fluorescence imaging experiments revealed that P-MHFn nanoparticles can accumulate in tumors, which suggests that P-MHFn could be used in tumor imaging and therapy. An acute toxicity study of P-MHFn in Sprague Dawley rats showed no abnormalities at a dose up to 20 mg Fe Kg[-1] body weight. Therefore, this study shed light on the development of magnetoferritin nanoparticles using therapeutic HFn expressed by Pichia pastoris for biomedical applications.}, } @article {pmid32930360, year = {2021}, author = {Salas-Vidal, E and Méndez-Cruz, FJ and Ramírez-Corona, A and Reza-Medina, B}, title = {Oxygen, reactive oxygen species and developmental redox networks: Evo-Devo Evil-Devils?.}, journal = {The International journal of developmental biology}, volume = {65}, number = {4-5-6}, pages = {345-356}, doi = {10.1387/ijdb.200170es}, pmid = {32930360}, issn = {1696-3547}, mesh = {Animals ; *Biological Evolution ; *Developmental Biology ; Oxidation-Reduction ; *Oxygen ; *Reactive Oxygen Species ; }, abstract = {Molecular oxygen (O2), reactive oxygen species (ROS), and associated redox networks are cornerstones of aerobic life. These molecules and networks have gained recognition as fundamental players in mechanisms that regulate the development of multicellular organisms. First, we present a brief review in which we provide a historical description of some relevant discoveries that led to this recognition. We also discuss the fact that, despite its abundance in nature, oxygen is a limiting factor, and its high availability variation impacted the evolution of adaptive mechanisms to guarantee the proper development of diverse species under such extreme environments. Finally, some examples of when oxygen and ROS were identified as relevant for the control of developmental processes are discussed. We take into account not only the current knowledge on animal redox developmental biology, but also briefly discuss potential scenarios on the origin and evolution of redox developmental mechanisms and the importance of the ever-changing environment.}, } @article {pmid32929605, year = {2020}, author = {Cui, Y and Zhao, H and Wu, S and Li, X}, title = {Human Female Reproductive System Organoids: Applications in Developmental Biology, Disease Modelling, and Drug Discovery.}, journal = {Stem cell reviews and reports}, volume = {16}, number = {6}, pages = {1173-1184}, doi = {10.1007/s12015-020-10039-0}, pmid = {32929605}, issn = {2629-3277}, mesh = {Animals ; *Developmental Biology ; Disease Models, Animal ; *Drug Discovery ; Female ; Genitalia, Female/*pathology ; Humans ; Organoids/*pathology ; Trophoblasts/pathology ; }, abstract = {Organoid technique has achieved significant progress in recent years, owing to the rapid development of the three-dimensional (3D) culture techniques in adult stem cells (ASCs) and pluripotent stem cells (PSCs) that are capable of self-renewal and induced differentiation. However, our understanding of human female reproductive system organoids is in its infancy. Recently, scientists have established self-organizing 3D organoids for human endometrium, fallopian tubes, oocyte, and trophoblasts by culturing stem cells with a cocktail of cytokines in a 3D scaffold. These organoids express multicellular biomarkers and show functional characteristics similar to those of their origin organs, which provide potential avenues to explore reproductive system development, disease modelling, and patient-specific therapy. Nevertheless, advanced culture methods, such as co-culture system, 3D bioprinting and organoid-on-a-chip technology, remain to be explored, and more efforts should be made for further elucidation of cell-cell crosstalk. This review describes the development and applications of human female reproductive system organoids. Graphical abstract Figure: Applications in developmental biology, disease modelling, and drug discovery of human female reproductive system organoids. ASCs: adult stem cells; PSCs: pluripotent stem cells.}, } @article {pmid32929365, year = {2020}, author = {Mowday, AM and Copp, JN and Syddall, SP and Dubois, LJ and Wang, J and Lieuwes, NG and Biemans, R and Ashoorzadeh, A and Abbattista, MR and Williams, EM and Guise, CP and Lambin, P and Ackerley, DF and Smaill, JB and Theys, J and Patterson, AV}, title = {E. coli nitroreductase NfsA is a reporter gene for non-invasive PET imaging in cancer gene therapy applications.}, journal = {Theranostics}, volume = {10}, number = {23}, pages = {10548-10562}, pmid = {32929365}, issn = {1838-7640}, mesh = {Animals ; Antineoplastic Agents, Alkylating/*pharmacology/therapeutic use ; Drug Resistance, Neoplasm ; Escherichia coli Proteins/*administration & dosage/genetics ; Etanidazole/administration & dosage/analogs & derivatives/pharmacokinetics ; *Genes, Reporter ; Genetic Therapy ; Genetic Vectors/administration & dosage/pharmacokinetics ; HCT116 Cells ; Humans ; Hydrocarbons, Fluorinated/administration & dosage/pharmacokinetics ; Imidazoles/administration & dosage ; Indicators and Reagents/administration & dosage/pharmacokinetics ; Mice ; Molecular Imaging/methods ; Neoplasms/*diagnostic imaging/drug therapy/genetics/pathology ; Nitrogen Mustard Compounds/pharmacology/therapeutic use ; Nitroreductases/*administration & dosage/genetics ; Positron-Emission Tomography/*methods ; Precision Medicine/methods ; Proof of Concept Study ; Radiopharmaceuticals/administration & dosage ; Recombinant Proteins/administration & dosage/genetics ; Triazoles/administration & dosage ; Tumor Hypoxia ; Xenograft Model Antitumor Assays ; }, abstract = {The use of reporter genes to non-invasively image molecular processes inside cells has significant translational potential, particularly in the context of systemically administered gene therapy vectors and adoptively administered cells such as immune or stem cell based therapies. Bacterial nitroreductase enzymes possess ideal properties for reporter gene imaging applications, being of non-human origin and possessing the ability to metabolize a range of clinically relevant nitro(hetero)cyclic substrates. Methods: A library of eleven Escherichia coli nitroreductase candidates were screened for the ability to efficiently metabolize 2-nitroimidazole based positron emission tomography (PET) probes originally developed as radiotracers for hypoxic cell imaging. Several complementary methods were utilized to detect formation of cell-entrapped metabolites, including various in vitro and in vivo models to establish the capacity of the 2-nitroimidazole PET agent EF5 to quantify expression of a nitroreductase candidate. Proof-of-principle PET imaging studies were successfully conducted using [18]F-HX4. Results: Recombinant enzyme kinetics, bacterial SOS reporter assays, anti-proliferative assays and flow cytometry approaches collectively identified the major oxygen-insensitive nitroreductase NfsA from E. coli (NfsA_Ec) as the most promising nitroreductase reporter gene. Cells expressing NfsA_Ec were demonstrably labelled with the imaging agent EF5 in a manner that was quantitatively superior to hypoxia, in monolayers (2D), multicellular layers (3D), and in human tumor xenograft models. EF5 retention correlated with NfsA_Ec positive cell density over a range of EF5 concentrations in 3D in vitro models and in xenografts in vivo and was predictive of in vivo anti-tumor activity of the cytotoxic prodrug PR-104. Following PET imaging with [18]F-HX4, a significantly higher tumor-to-blood ratio was observed in two xenograft models for NfsA_Ec expressing tumors compared to the parental tumors thereof, providing verification of this reporter gene imaging approach. Conclusion: This study establishes that the bacterial nitroreductase NfsA_Ec can be utilized as an imaging capable reporter gene, with the ability to metabolize and trap 2-nitroimidazole PET imaging agents for non-invasive imaging of gene expression.}, } @article {pmid32802320, year = {2020}, author = {Cohen, IR and Marron, A}, title = {The evolution of universal adaptations of life is driven by universal properties of matter: energy, entropy, and interaction.}, journal = {F1000Research}, volume = {9}, number = {}, pages = {626}, pmid = {32802320}, issn = {2046-1402}, mesh = {*Adaptation, Biological ; Animals ; *Entropy ; Humans ; Metabolic Networks and Pathways ; Microbiota ; Phenotype ; *Reproduction ; }, abstract = {The evolution of multicellular eukaryotes expresses two sorts of adaptations: local adaptations like fur or feathers, which characterize species in particular environments, and universal adaptations like microbiomes or sexual reproduction, which characterize most multicellulars in any environment. We reason that the mechanisms driving the universal adaptations of multicellulars should themselves be universal, and propose a mechanism based on properties of matter and systems: energy, entropy, and interaction. Energy from the sun, earth and beyond creates new arrangements and interactions. Metabolic networks channel some of this energy to form cooperating, interactive arrangements. Entropy, used here as a term for all forces that dismantle ordered structures (rather than as a physical quantity), acts as a selective force. Entropy selects for arrangements that resist it long enough to replicate, and dismantles those that do not. Interactions, energy-charged and dynamic, restrain entropy and enable survival and propagation of integrated living systems. This fosters survival-of-the-fitted - those entities that resist entropic destruction - and not only of the fittest - the entities with the greatest reproductive success. The "unit" of evolution is not a discrete entity, such as a gene, individual, or species; what evolves are collections of related interactions at multiple scales. Survival-of-the-fitted explains universal adaptations, including resident microbiomes, sexual reproduction, continuous diversification, programmed turnover, seemingly wasteful phenotypes, altruism, co-evolving environmental niches, and advancing complexity. Indeed survival-of-the-fittest may be a particular case of the survival-of-the-fitted mechanism, promoting local adaptations that express reproductive advantages in addition to resisting entropy. Survival-of-the-fitted accounts for phenomena that have been attributed to neutral evolution: in the face of entropy, there is no neutrality; all variations are challenged by ubiquitous energy and entropy, retaining those that are "fit enough". We propose experiments to test predictions of the survival-of-the-fitted theory, and discuss implications for the wellbeing of humans and the biosphere.}, } @article {pmid32918875, year = {2020}, author = {Funato, Y and Yoshida, A and Hirata, Y and Hashizume, O and Yamazaki, D and Miki, H}, title = {The Oncogenic PRL Protein Causes Acid Addiction of Cells by Stimulating Lysosomal Exocytosis.}, journal = {Developmental cell}, volume = {55}, number = {4}, pages = {387-397.e8}, doi = {10.1016/j.devcel.2020.08.009}, pmid = {32918875}, issn = {1878-1551}, mesh = {Acids/*metabolism ; Animals ; CRISPR-Cas Systems/genetics ; Caenorhabditis elegans/metabolism ; Conserved Sequence ; Dogs ; Evolution, Molecular ; *Exocytosis ; HEK293 Cells ; Humans ; Immediate-Early Proteins/*metabolism ; Intracellular Membranes/metabolism ; Lysosomes/*metabolism ; Madin Darby Canine Kidney Cells ; Mice, Inbred C57BL ; Neoplasm Metastasis ; Neoplasm Proteins/*metabolism ; Protein Tyrosine Phosphatases/*metabolism ; }, abstract = {Extracellular pH is usually maintained around 7.4 in multicellular organisms, and cells are optimized to proliferate under this condition. Here, we find cells can adapt to a more acidic pH of 6.5 and become addicted to this acidic microenvironment by expressing phosphatase of regenerating liver (PRL), a driver of cancer malignancy. Genome-scale CRISPR-Cas9 knockout screening and subsequent analyses revealed that PRL promotes H[+] extrusion and acid addiction by stimulating lysosomal exocytosis. Further experiments using cultured cells and Caenorhabditis elegans clarified the molecular link between PRL and lysosomal exocytosis across species, involving activation of lysosomal Ca[2+] channel TRPML by ROS. Indeed, disruption of TRPML in cancer cells abolished PRL-stimulated lysosomal exocytosis, acid addiction, and metastasis. Thus, PRL is the molecular switch turning cells addicted to an acidic condition, which should benefit cancer cells to thrive in an acidic tumor microenvironment.}, } @article {pmid32914530, year = {2020}, author = {Gao, M and Mackley, IGP and Mesbahi-Vasey, S and Bamonte, HA and Struyvenberg, SA and Landolt, L and Pederson, NJ and Williams, LI and Bahl, CD and Brooks, L and Amacher, JF}, title = {Structural characterization and computational analysis of PDZ domains in Monosiga brevicollis.}, journal = {Protein science : a publication of the Protein Society}, volume = {29}, number = {11}, pages = {2226-2244}, pmid = {32914530}, issn = {1469-896X}, support = {S10OD021832/NH/NIH HHS/United States ; S10 OD021832/OD/NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {*Algorithms ; Choanoflagellata/*chemistry/genetics ; Crystallography, X-Ray ; Databases, Protein ; *Models, Molecular ; *PDZ Domains ; Protozoan Proteins/*chemistry/genetics ; *Sequence Analysis, Protein ; }, abstract = {Identification of the molecular networks that facilitated the evolution of multicellular animals from their unicellular ancestors is a fundamental problem in evolutionary cellular biology. Choanoflagellates are recognized as the closest extant nonmetazoan ancestors to animals. These unicellular eukaryotes can adopt a multicellular-like "rosette" state. Therefore, they are compelling models for the study of early multicellularity. Comparative studies revealed that a number of putative human orthologs are present in choanoflagellate genomes, suggesting that a subset of these genes were necessary for the emergence of multicellularity. However, previous work is largely based on sequence alignments alone, which does not confirm structural nor functional similarity. Here, we focus on the PDZ domain, a peptide-binding domain which plays critical roles in myriad cellular signaling networks and which underwent a gene family expansion in metazoan lineages. Using a customized sequence similarity search algorithm, we identified 178 PDZ domains in the Monosiga brevicollis proteome. This includes 11 previously unidentified sequences, which we analyzed using Rosetta and homology modeling. To assess conservation of protein structure, we solved high-resolution crystal structures of representative M. brevicollis PDZ domains that are homologous to human Dlg1 PDZ2, Dlg1 PDZ3, GIPC, and SHANK1 PDZ domains. To assess functional conservation, we calculated binding affinities for mbGIPC, mbSHANK1, mbSNX27, and mbDLG-3 PDZ domains from M. brevicollis. Overall, we find that peptide selectivity is generally conserved between these two disparate organisms, with one possible exception, mbDLG-3. Overall, our results provide novel insight into signaling pathways in a choanoflagellate model of primitive multicellularity.}, } @article {pmid32900997, year = {2020}, author = {Fukushima, K and Pollock, DD}, title = {Amalgamated cross-species transcriptomes reveal organ-specific propensity in gene expression evolution.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {4459}, pmid = {32900997}, issn = {2041-1723}, support = {R01 GM083127/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Databases, Nucleic Acid ; *Evolution, Molecular ; Female ; Gene Duplication ; Humans ; Male ; Models, Genetic ; Multigene Family ; Organ Specificity ; Phylogeny ; Proteins/genetics ; RNA-Seq ; Species Specificity ; *Transcriptome ; Vertebrates/classification/genetics ; }, abstract = {The origins of multicellular physiology are tied to evolution of gene expression. Genes can shift expression as organisms evolve, but how ancestral expression influences altered descendant expression is not well understood. To examine this, we amalgamate 1,903 RNA-seq datasets from 182 research projects, including 6 organs in 21 vertebrate species. Quality control eliminates project-specific biases, and expression shifts are reconstructed using gene-family-wise phylogenetic Ornstein-Uhlenbeck models. Expression shifts following gene duplication result in more drastic changes in expression properties than shifts without gene duplication. The expression properties are tightly coupled with protein evolutionary rate, depending on whether and how gene duplication occurred. Fluxes in expression patterns among organs are nonrandom, forming modular connections that are reshaped by gene duplication. Thus, if expression shifts, ancestral expression in some organs induces a strong propensity for expression in particular organs in descendants. Regardless of whether the shifts are adaptive or not, this supports a major role for what might be termed preadaptive pathways of gene expression evolution.}, } @article {pmid32889101, year = {2020}, author = {Sidorova, A and Tverdislov, V and Levashova, N and Garaeva, A}, title = {A model of autowave self-organization as a hierarchy of active media in the biological evolution.}, journal = {Bio Systems}, volume = {198}, number = {}, pages = {104234}, doi = {10.1016/j.biosystems.2020.104234}, pmid = {32889101}, issn = {1872-8324}, mesh = {*Algorithms ; *Biological Evolution ; Eukaryota/*classification/cytology/genetics ; *Genetic Speciation ; Genome/genetics ; *Models, Theoretical ; Mutation/genetics ; Prokaryotic Cells/*classification/metabolism ; Species Specificity ; Time Factors ; }, abstract = {Within the framework of the active media concept, we develop a biophysical model of autowave self-organization which is treated as a hierarchy of active media in the evolution of the biosphere. We also propose a mathematical model of the autowave process of speciation in a flow of mutations for the three main taxonometric groups (prokaryotes, unicellular and multicellular eukaryotes) with a naturally determined lower boundary of living matter (the appearance of prokaryotes) and an open upper boundary for the formation of new species. It is shown that the fluctuation-bifurcation description of the evolution for the formation of new taxonometric groups as a trajectory of transformation of small fluctuations into giant ones adequately reflects the process of self-organization during the formation of taxa. The major concepts of biological evolution, conditions of hierarchy formation as a fundamental manifestation of self-organization and complexity in the evolution of biological systems are considered.}, } @article {pmid32888478, year = {2020}, author = {Pentz, JT and Márquez-Zacarías, P and Bozdag, GO and Burnetti, A and Yunker, PJ and Libby, E and Ratcliff, WC}, title = {Ecological Advantages and Evolutionary Limitations of Aggregative Multicellular Development.}, journal = {Current biology : CB}, volume = {30}, number = {21}, pages = {4155-4164.e6}, doi = {10.1016/j.cub.2020.08.006}, pmid = {32888478}, issn = {1879-0445}, mesh = {*Biological Evolution ; Cell Adhesion/*physiology ; *Models, Biological ; Saccharomyces cerevisiae/*growth & development ; }, abstract = {All multicellular organisms develop through one of two basic routes: they either aggregate from free-living cells, creating potentially chimeric multicellular collectives, or they develop clonally via mother-daughter cellular adhesion. Although evolutionary theory makes clear predictions about trade-offs between these developmental modes, these have never been experimentally tested in otherwise genetically identical organisms. We engineered unicellular baker's yeast (Saccharomyces cerevisiae) to develop either clonally ("snowflake"; Δace2) or aggregatively ("floc"; GAL1p::FLO1) and examined their fitness in a fluctuating environment characterized by periods of growth and selection for rapid sedimentation. When cultured independently, aggregation was far superior to clonal development, providing a 35% advantage during growth and a 2.5-fold advantage during settling selection. Yet when competed directly, clonally developing snowflake yeast rapidly displaced aggregative floc. This was due to unexpected social exploitation: snowflake yeast, which do not produce adhesive FLO1, nonetheless become incorporated into flocs at a higher frequency than floc cells themselves. Populations of chimeric clusters settle much faster than floc alone, providing snowflake yeast with a fitness advantage during competition. Mathematical modeling suggests that such developmental cheating may be difficult to circumvent; hypothetical "choosy floc" that avoid exploitation by maintaining clonality pay an ecological cost when rare, often leading to their extinction. Our results highlight the conflict at the heart of aggregative development: non-specific cellular binding provides a strong ecological advantage-the ability to quickly form groups-but this very feature leads to its exploitation.}, } @article {pmid32882615, year = {2020}, author = {Ruiz-Arrebola, S and Tornero-López, AM and Guirado, D and Villalobos, M and Lallena, AM}, title = {An on-lattice agent-based Monte Carlo model simulating the growth kinetics of multicellular tumor spheroids.}, journal = {Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB)}, volume = {77}, number = {}, pages = {194-203}, doi = {10.1016/j.ejmp.2020.07.026}, pmid = {32882615}, issn = {1724-191X}, mesh = {*Breast Neoplasms ; Female ; Humans ; Kinetics ; Monte Carlo Method ; Necrosis ; *Spheroids, Cellular ; }, abstract = {PURPOSE: To develop an on-lattice agent-based model describing the growth of multicellular tumor spheroids using simple Monte Carlo tools.

METHODS: Cells are situated on the vertices of a cubic grid. Different cell states (proliferative, hypoxic or dead) and cell evolution rules, driven by 10 parameters, and the effects of the culture medium are included. About twenty spheroids of MCF-7 human breast cancer were cultivated and the experimental data were used for tuning the model parameters.

RESULTS: Simulated spheroids showed adequate sizes of the necrotic nuclei and of the hypoxic and proliferative cell phases as a function of the growth time, mimicking the overall characteristics of the experimental spheroids. The relation between the radii of the necrotic nucleus and the whole spheroid obtained in the simulations was similar to the experimental one and the number of cells, as a function of the spheroid volume, was well reproduced. The statistical variability of the Monte Carlo model described the whole volume range observed for the experimental spheroids. Assuming that the model parameters vary within Gaussian distributions it was obtained a sample of spheroids that reproduced much better the experimental findings.

CONCLUSIONS: The model developed allows describing the growth of in vitro multicellular spheroids and the experimental variability can be well reproduced. Its flexibility permits to vary both the agents involved and the rules that govern the spheroid growth. More general situations, such as, e. g., tumor vascularization, radiotherapy effects on solid tumors, or the validity of the tumor growth mathematical models can be studied.}, } @article {pmid32873627, year = {2021}, author = {Saucedo, LJ and Triolo, RE and Segar, KE}, title = {How Drosophila Can Inform the Emerging Paradigm of the Role of Antioxidants in Cancer.}, journal = {Molecular cancer research : MCR}, volume = {19}, number = {1}, pages = {38-41}, doi = {10.1158/1541-7786.MCR-20-0172}, pmid = {32873627}, issn = {1557-3125}, mesh = {Animals ; Antioxidants/*metabolism ; Drosophila melanogaster/*genetics ; Humans ; Neoplasms/*genetics ; }, abstract = {Drosophila melanogaster has proven to be an effective model system in uncovering both genetic and cellular contributions to human cancer. Many elusive genes and signaling pathways that control oncogenic growth were first identified using flies. In many cases, these discoveries were not driven by a direct search for novel genes involved in cancer but rather stemmed from research programs to uncover mechanisms that control growth and development. However, the bounty of genetic tools and the shared evolution of multicellular organisms places Drosophila in a powerful position to purposefully elucidate observations seen in human cancers. In the past decade, the role of antioxidants in cancer progression has shifted dramatically. This review highlights major findings driving this change in perspective and underscores an array of existing work and resources in laboratories using Drosophila that can make significant contributions to how the redox environment affects cancer progression.}, } @article {pmid32871001, year = {2021}, author = {Futo, M and Opašić, L and Koska, S and Čorak, N and Široki, T and Ravikumar, V and Thorsell, A and Lenuzzi, M and Kifer, D and Domazet-Lošo, M and Vlahoviček, K and Mijakovic, I and Domazet-Lošo, T}, title = {Embryo-Like Features in Developing Bacillus subtilis Biofilms.}, journal = {Molecular biology and evolution}, volume = {38}, number = {1}, pages = {31-47}, pmid = {32871001}, issn = {1537-1719}, mesh = {Bacillus subtilis/cytology/*physiology ; *Biofilms ; *Biological Evolution ; }, abstract = {Correspondence between evolution and development has been discussed for more than two centuries. Recent work reveals that phylogeny-ontogeny correlations are indeed present in developmental transcriptomes of eukaryotic clades with complex multicellularity. Nevertheless, it has been largely ignored that the pervasive presence of phylogeny-ontogeny correlations is a hallmark of development in eukaryotes. This perspective opens a possibility to look for similar parallelisms in biological settings where developmental logic and multicellular complexity are more obscure. For instance, it has been increasingly recognized that multicellular behavior underlies biofilm formation in bacteria. However, it remains unclear whether bacterial biofilm growth shares some basic principles with development in complex eukaryotes. Here we show that the ontogeny of growing Bacillus subtilis biofilms recapitulates phylogeny at the expression level. Using time-resolved transcriptome and proteome profiles, we found that biofilm ontogeny correlates with the evolutionary measures, in a way that evolutionary younger and more diverged genes were increasingly expressed toward later timepoints of biofilm growth. Molecular and morphological signatures also revealed that biofilm growth is highly regulated and organized into discrete ontogenetic stages, analogous to those of eukaryotic embryos. Together, this suggests that biofilm formation in Bacillus is a bona fide developmental process comparable to organismal development in animals, plants, and fungi. Given that most cells on Earth reside in the form of biofilms and that biofilms represent the oldest known fossils, we anticipate that the widely adopted vision of the first life as a single-cell and free-living organism needs rethinking.}, } @article {pmid32861802, year = {2020}, author = {Stewart, JE}, title = {Towards a general theory of the major cooperative evolutionary transitions.}, journal = {Bio Systems}, volume = {198}, number = {}, pages = {104237}, doi = {10.1016/j.biosystems.2020.104237}, pmid = {32861802}, issn = {1872-8324}, mesh = {Adaptation, Physiological/*physiology ; *Biological Evolution ; *Communication ; *Cooperative Behavior ; Humans ; Political Systems ; Public Policy ; Social Behavior ; Socioeconomic Factors ; }, abstract = {Major Cooperative Evolutionary Transitions occur when smaller-scale entities cooperate together to give rise to larger-scale entities that evolve and adapt as coherent wholes. Key examples of cooperative transitions are the emergence of the complex eukaryote cell from communities of simpler cells, the transition from eukaryote cells to multicellular organisms, and the organization of humans into complex, modern societies. A number of attempts have been made to develop a general theory of the major cooperative transitions. This paper begins by critiquing key aspects of these previous attempts. Largely, these attempts comprise poorly-integrated collections of separate models that were each originally developed to explain particular transitions. In contrast, this paper sets out to identify processes that are common to all cooperative transitions. It develops an alternative theoretical framework known as Management Theory. This general framework suggests that all major cooperative transitions are the result of the emergence of powerful, evolvable 'managers' that derive benefit from using their power to organize smaller-scale entities into larger-scale cooperatives. Management Theory is a contribution to the development of a general, "all levels" understanding of major cooperative transitions that is capable of identifying those features that are level-specific, those that are common across levels and those that are involved in trends across levels.}, } @article {pmid32857975, year = {2020}, author = {Parra-Acero, H and Harcet, M and Sánchez-Pons, N and Casacuberta, E and Brown, NH and Dudin, O and Ruiz-Trillo, I}, title = {Integrin-Mediated Adhesion in the Unicellular Holozoan Capsaspora owczarzaki.}, journal = {Current biology : CB}, volume = {30}, number = {21}, pages = {4270-4275.e4}, doi = {10.1016/j.cub.2020.08.015}, pmid = {32857975}, issn = {1879-0445}, mesh = {CD18 Antigens/metabolism ; Cell Adhesion/*physiology ; Eukaryota/cytology/*physiology ; Fibronectins/metabolism ; Integrins/metabolism ; Pseudopodia/metabolism ; Vinculin/metabolism ; }, abstract = {In animals, cell-matrix adhesions are essential for cell migration, tissue organization, and differentiation, which have central roles in embryonic development [1-6]. Integrins are the major cell surface adhesion receptors mediating cell-matrix adhesion in animals. They are heterodimeric transmembrane proteins that bind extracellular matrix (ECM) molecules on one side and connect to the actin cytoskeleton on the other [7]. Given the importance of integrin-mediated cell-matrix adhesion in development of multicellular animals, it is of interest to discover when and how this machinery arose during evolution. Comparative genomic analyses have shown that core components of the integrin adhesome pre-date the emergence of animals [8-11]; however, whether it mediates cell adhesion in non-metazoan taxa remains unknown. Here, we investigate cell-substrate adhesion in Capsaspora owczarzaki, the closest unicellular relative of animals with the most complete integrin adhesome [11, 12]. Previous work described that the life cycle of C. owczarzaki (hereafter, Capsaspora) includes three distinct life stages: adherent; cystic; and aggregative [13]. Using an adhesion assay, we show that, during the adherent life stage, C. owczarzaki adheres to surfaces using actin-dependent filopodia. We show that integrin β2 and its associated protein vinculin localize as distinct patches in the filopodia. We also demonstrate that substrate adhesion and integrin localization are enhanced by mammalian fibronectin. Finally, using a specific antibody for integrin β2, we inhibited cell adhesion to a fibronectin-coated surface. Our results suggest that adhesion to the substrate in C. owczarzaki is mediated by integrins. We thus propose that integrin-mediated adhesion pre-dates the emergence of animals.}, } @article {pmid32849605, year = {2020}, author = {Pérez-Hernández, CA and Kern, CC and Butkeviciute, E and McCarthy, E and Dockrell, HM and Moreno-Altamirano, MMB and Aguilar-López, BA and Bhosale, G and Wang, H and Gems, D and Duchen, MR and Smith, SG and Sánchez-García, FJ}, title = {Mitochondrial Signature in Human Monocytes and Resistance to Infection in C. elegans During Fumarate-Induced Innate Immune Training.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {1715}, pmid = {32849605}, issn = {1664-3224}, support = {MR/R005850/1/MRC_/Medical Research Council/United Kingdom ; /BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; 098565/Z/12/Z/WT_/Wellcome Trust/United Kingdom ; 215574/Z/19/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Caenorhabditis elegans/*drug effects/immunology/metabolism/microbiology ; Calcium Signaling/drug effects ; Cells, Cultured ; Cytokines/metabolism ; Escherichia coli/immunology/*pathogenicity ; Escherichia coli Infections/immunology/metabolism/microbiology/*prevention & control ; Fumarates/*pharmacology ; Host-Pathogen Interactions ; Humans ; Immunity, Innate/*drug effects ; Immunologic Memory/*drug effects ; Membrane Potential, Mitochondrial/drug effects ; Mitochondria/*drug effects/immunology/metabolism ; Mitochondrial Dynamics/drug effects ; Monocytes/*drug effects/immunology/metabolism ; }, abstract = {Monocytes can develop immunological memory, a functional characteristic widely recognized as innate immune training, to distinguish it from memory in adaptive immune cells. Upon a secondary immune challenge, either homologous or heterologous, trained monocytes/macrophages exhibit a more robust production of pro-inflammatory cytokines, such as IL-1β, IL-6, and TNF-α, than untrained monocytes. Candida albicans, β-glucan, and BCG are all inducers of monocyte training and recent metabolic profiling analyses have revealed that training induction is dependent on glycolysis, glutaminolysis, and the cholesterol synthesis pathway, along with fumarate accumulation; interestingly, fumarate itself can induce training. Since fumarate is produced by the tricarboxylic acid (TCA) cycle within mitochondria, we asked whether extra-mitochondrial fumarate has an effect on mitochondrial function. Results showed that the addition of fumarate to monocytes induces mitochondrial Ca[2+] uptake, fusion, and increased membrane potential (Δψm), while mitochondrial cristae became closer to each other, suggesting that immediate (from minutes to hours) mitochondrial activation plays a role in the induction phase of innate immune training of monocytes. To establish whether fumarate induces similar mitochondrial changes in vivo in a multicellular organism, effects of fumarate supplementation were tested in the nematode worm Caenorhabditis elegans. This induced mitochondrial fusion in both muscle and intestinal cells and also increased resistance to infection of the pharynx with E. coli. Together, these findings contribute to defining a mitochondrial signature associated with the induction of innate immune training by fumarate treatment, and to the understanding of whole organism infection resistance.}, } @article {pmid32839450, year = {2020}, author = {Du, P and Zhao, H and Zhang, H and Wang, R and Huang, J and Tian, Y and Luo, X and Luo, X and Wang, M and Xiang, Y and Qian, L and Chen, Y and Tao, Y and Lou, C}, title = {De novo design of an intercellular signaling toolbox for multi-channel cell-cell communication and biological computation.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {4226}, pmid = {32839450}, issn = {2041-1723}, mesh = {Cell Communication/*genetics ; Computational Biology/*methods ; Escherichia coli/genetics/metabolism ; Green Fluorescent Proteins/genetics/metabolism ; HEK293 Cells ; Humans ; Microscopy, Fluorescence ; Mutation ; Reproducibility of Results ; Saccharomyces cerevisiae/genetics/metabolism ; Signal Transduction/*genetics ; Transcription Factors/*genetics/metabolism ; }, abstract = {Intercellular signaling is indispensable for single cells to form complex biological structures, such as biofilms, tissues and organs. The genetic tools available for engineering intercellular signaling, however, are quite limited. Here we exploit the chemical diversity of biological small molecules to de novo design a genetic toolbox for high-performance, multi-channel cell-cell communications and biological computations. By biosynthetic pathway design for signal molecules, rational engineering of sensing promoters and directed evolution of sensing transcription factors, we obtain six cell-cell signaling channels in bacteria with orthogonality far exceeding the conventional quorum sensing systems and successfully transfer some of them into yeast and human cells. For demonstration, they are applied in cell consortia to generate bacterial colony-patterns using up to four signaling channels simultaneously and to implement distributed bio-computation containing seven different strains as basic units. This intercellular signaling toolbox paves the way for engineering complex multicellularity including artificial ecosystems and smart tissues.}, } @article {pmid32822576, year = {2020}, author = {Maynard, A and McCoach, CE and Rotow, JK and Harris, L and Haderk, F and Kerr, DL and Yu, EA and Schenk, EL and Tan, W and Zee, A and Tan, M and Gui, P and Lea, T and Wu, W and Urisman, A and Jones, K and Sit, R and Kolli, PK and Seeley, E and Gesthalter, Y and Le, DD and Yamauchi, KA and Naeger, DM and Bandyopadhyay, S and Shah, K and Cech, L and Thomas, NJ and Gupta, A and Gonzalez, M and Do, H and Tan, L and Bacaltos, B and Gomez-Sjoberg, R and Gubens, M and Jahan, T and Kratz, JR and Jablons, D and Neff, N and Doebele, RC and Weissman, J and Blakely, CM and Darmanis, S and Bivona, TG}, title = {Therapy-Induced Evolution of Human Lung Cancer Revealed by Single-Cell RNA Sequencing.}, journal = {Cell}, volume = {182}, number = {5}, pages = {1232-1251.e22}, pmid = {32822576}, issn = {1097-4172}, support = {R01 CA227807/CA/NCI NIH HHS/United States ; T32 HL007185/HL/NHLBI NIH HHS/United States ; U54 CA224081/CA/NCI NIH HHS/United States ; R01 CA211052/CA/NCI NIH HHS/United States ; U01 CA217882/CA/NCI NIH HHS/United States ; 2018110/DDCF_/Doris Duke Charitable Foundation/United States ; R01 CA231300/CA/NCI NIH HHS/United States ; R01 CA169338/CA/NCI NIH HHS/United States ; R01 CA204302/CA/NCI NIH HHS/United States ; K12 CA086913/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers, Tumor/genetics ; Cell Line ; Ecosystem ; Humans ; Lung Neoplasms/*genetics/pathology ; Macrophages/pathology ; Sequence Analysis, RNA/methods ; Single-Cell Analysis/methods ; T-Lymphocytes/pathology ; Tumor Microenvironment/genetics ; }, abstract = {Lung cancer, the leading cause of cancer mortality, exhibits heterogeneity that enables adaptability, limits therapeutic success, and remains incompletely understood. Single-cell RNA sequencing (scRNA-seq) of metastatic lung cancer was performed using 49 clinical biopsies obtained from 30 patients before and during targeted therapy. Over 20,000 cancer and tumor microenvironment (TME) single-cell profiles exposed a rich and dynamic tumor ecosystem. scRNA-seq of cancer cells illuminated targetable oncogenes beyond those detected clinically. Cancer cells surviving therapy as residual disease (RD) expressed an alveolar-regenerative cell signature suggesting a therapy-induced primitive cell-state transition, whereas those present at on-therapy progressive disease (PD) upregulated kynurenine, plasminogen, and gap-junction pathways. Active T-lymphocytes and decreased macrophages were present at RD and immunosuppressive cell states characterized PD. Biological features revealed by scRNA-seq were biomarkers of clinical outcomes in independent cohorts. This study highlights how therapy-induced adaptation of the multi-cellular ecosystem of metastatic cancer shapes clinical outcomes.}, } @article {pmid32810421, year = {2020}, author = {Grassam-Rowe, A and Ou, X and Lei, M}, title = {Novel cardiac cell subpopulations: Pnmt-derived cardiomyocytes.}, journal = {Open biology}, volume = {10}, number = {8}, pages = {200095}, pmid = {32810421}, issn = {2046-2441}, support = {G1002082/MRC_/Medical Research Council/United Kingdom ; PG/14/80/31106/BHF_/British Heart Foundation/United Kingdom ; G10002647/MRC_/Medical Research Council/United Kingdom ; G1002647/MRC_/Medical Research Council/United Kingdom ; PG/11/59/29004/BHF_/British Heart Foundation/United Kingdom ; PG/16/67/32340/BHF_/British Heart Foundation/United Kingdom ; PG/12/21/29473/BHF_/British Heart Foundation/United Kingdom ; }, mesh = {Age Factors ; Animals ; Biomarkers ; Catecholamines/metabolism ; *Cell Plasticity ; Electrophysiological Phenomena ; Humans ; Myocardium/cytology/enzymology/metabolism ; Myocytes, Cardiac/*cytology/*metabolism ; Organogenesis/genetics ; Phenotype ; Phenylethanolamine N-Methyltransferase/genetics/*metabolism ; }, abstract = {Diversity among highly specialized cells underlies the fundamental biology of complex multi-cellular organisms. One of the essential scientific questions in cardiac biology has been to define subpopulations within the heart. The heart parenchyma comprises specialized cardiomyocytes (CMs). CMs have been canonically classified into a few phenotypically diverse subpopulations largely based on their function and anatomic localization. However, there is growing evidence that CM subpopulations are in fact numerous, with a diversity of genetic origin and putatively different roles in physiology and pathophysiology. In this chapter, we introduce a recently discovered CM subpopulation: phenylethanolamine-N-methyl transferase (Pnmt)-derived cardiomyocytes (PdCMs). We discuss: (i) canonical classifications of CM subpopulations; (ii) discovery of PdCMs; (iii) Pnmt and the role of catecholamines in the heart; similarities and dissimilarities of PdCMs and canonical CMs; and (iv) putative functions of PdCMs in both physiological and pathological states and future directions, such as in intra-cardiac adrenergic signalling.}, } @article {pmid32797190, year = {2021}, author = {Ho, AT and Hurst, LD}, title = {Effective Population Size Predicts Local Rates but Not Local Mitigation of Read-through Errors.}, journal = {Molecular biology and evolution}, volume = {38}, number = {1}, pages = {244-262}, pmid = {32797190}, issn = {1537-1719}, mesh = {Arabidopsis ; *Codon, Terminator ; Dictyostelium ; *Evolution, Molecular ; *Mutation Rate ; Population Density ; *Selection, Genetic ; }, abstract = {In correctly predicting that selection efficiency is positively correlated with the effective population size (Ne), the nearly neutral theory provides a coherent understanding of between-species variation in numerous genomic parameters, including heritable error (germline mutation) rates. Does the same theory also explain variation in phenotypic error rates and in abundance of error mitigation mechanisms? Translational read-through provides a model to investigate both issues as it is common, mostly nonadaptive, and has good proxy for rate (TAA being the least leaky stop codon) and potential error mitigation via "fail-safe" 3' additional stop codons (ASCs). Prior theory of translational read-through has suggested that when population sizes are high, weak selection for local mitigation can be effective thus predicting a positive correlation between ASC enrichment and Ne. Contra to prediction, we find that ASC enrichment is not correlated with Ne. ASC enrichment, although highly phylogenetically patchy, is, however, more common both in unicellular species and in genes expressed in unicellular modes in multicellular species. By contrast, Ne does positively correlate with TAA enrichment. These results imply that local phenotypic error rates, not local mitigation rates, are consistent with a drift barrier/nearly neutral model.}, } @article {pmid32778581, year = {2020}, author = {Xin, Y and Le Poul, Y and Ling, L and Museridze, M and Mühling, B and Jaenichen, R and Osipova, E and Gompel, N}, title = {Enhancer evolutionary co-option through shared chromatin accessibility input.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {117}, number = {34}, pages = {20636-20644}, pmid = {32778581}, issn = {1091-6490}, mesh = {Animals ; Biological Evolution ; Chromatin/genetics/metabolism ; Drosophila Proteins/*genetics/metabolism ; Drosophila melanogaster/genetics ; Enhancer Elements, Genetic/*genetics ; Evolution, Molecular ; Gene Expression Regulation, Developmental/*genetics ; Regulatory Elements, Transcriptional/genetics ; Wings, Animal/metabolism ; }, abstract = {The diversity of forms in multicellular organisms originates largely from the spatial redeployment of developmental genes [S. B. Carroll, Cell 134, 25-36 (2008)]. Several scenarios can explain the emergence of cis-regulatory elements that govern novel aspects of a gene expression pattern [M. Rebeiz, M. Tsiantis, Curr. Opin. Genet. Dev. 45, 115-123 (2017)]. One scenario, enhancer co-option, holds that a DNA sequence producing an ancestral regulatory activity also becomes the template for a new regulatory activity, sharing regulatory information. While enhancer co-option might fuel morphological diversification, it has rarely been documented [W. J. Glassford et al., Dev. Cell 34, 520-531 (2015)]. Moreover, if two regulatory activities are borne from the same sequence, their modularity, considered a defining feature of enhancers [J. Banerji, L. Olson, W. Schaffner, Cell 33, 729-740 (1983)], might be affected by pleiotropy. Sequence overlap may thereby play a determinant role in enhancer function and evolution. Here, we investigated this problem with two regulatory activities of the Drosophila gene yellow, the novel spot enhancer and the ancestral wing blade enhancer. We used precise and comprehensive quantification of each activity in Drosophila wings to systematically map their sequences along the locus. We show that the spot enhancer has co-opted the sequences of the wing blade enhancer. We also identified a pleiotropic site necessary for DNA accessibility of a shared regulatory region. While the evolutionary steps leading to the derived activity are still unknown, such pleiotropy suggests that enhancer accessibility could be one of the molecular mechanisms seeding evolutionary co-option.}, } @article {pmid32767819, year = {2020}, author = {Kundu, R}, title = {Cationic Amphiphilic Peptides: Synthetic Antimicrobial Agents Inspired by Nature.}, journal = {ChemMedChem}, volume = {15}, number = {20}, pages = {1887-1896}, doi = {10.1002/cmdc.202000301}, pmid = {32767819}, issn = {1860-7187}, mesh = {Amino Acid Sequence ; Anti-Bacterial Agents/chemistry/*pharmacology/therapeutic use ; Antimicrobial Cationic Peptides/chemistry/*pharmacology/therapeutic use ; Bacteria/drug effects ; Clinical Trials as Topic ; Humans ; Lipopeptides/chemistry/pharmacology/therapeutic use ; Peptides, Cyclic/chemistry/pharmacology/therapeutic use ; Peptidomimetics/chemistry/pharmacology/therapeutic use ; Protein Conformation, alpha-Helical ; }, abstract = {Antimicrobial peptides are ubiquitous in multicellular organisms and have served as defense mechanisms for their successful evolution and throughout their life cycle. These peptides are short cationic amphiphilic polypeptides of fewer than 50 amino acids containing either a few disulfide-linked cysteine residues with a characteristic β-sheet-rich structure or linear α-helical conformations with hydrophilic side chains at one side of the helix and hydrophobic side chains on the other side. Antimicrobial peptides cause bacterial cell lysis either by direct cell-surface damage via electrostatic interactions between the cationic side chains of the peptide and the negatively charged cell surface, or by indirect modulation of the host defense systems. Electrostatic interactions lead to bacterial cell membrane disruption followed by leakage of cellular components and finally bacterial cell death. Because of their unusual mechanism of cell damage, antimicrobial peptides are effective against drug-resistant bacteria and may therefore prove more effective than classical antibiotics in certain cases. Currently, around 3000 natural antimicrobial peptides from six kingdoms (bacteria, archaea, protists, fungi, plants, and animals) have been isolated and sequenced. However, only a few of them are under clinical trials and/or in the commercial development stage for the treatment of bacterial infections caused by antibiotic-resistant bacteria. Moreover, high structural complexity, poor pharmacokinetic properties, and low antibacterial activity of natural antimicrobial peptides hinder their progress in drug development. To overcome these hurdles, researchers have become increasingly interested in modification and nature-inspired synthetic antimicrobial peptides. This review discusses some of the recent studies reported on antimicrobial peptides.}, } @article {pmid32762341, year = {2020}, author = {Whelan, CJ and Avdieiev, SS and Gatenby, RA}, title = {Insights From the Ecology of Information to Cancer Control.}, journal = {Cancer control : journal of the Moffitt Cancer Center}, volume = {27}, number = {3}, pages = {1073274820945980}, pmid = {32762341}, issn = {1526-2359}, support = {U54 CA193489/CA/NCI NIH HHS/United States ; }, mesh = {Cytoskeleton/physiology ; *Ecosystem ; Humans ; Integrins/physiology ; Models, Theoretical ; Neoplasms/pathology/*therapy ; Tumor Microenvironment ; }, abstract = {Uniquely in nature, living systems must acquire, store, and act upon information. The survival and replicative fate of each normal cell in a multicellular organism is determined solely by information obtained from its surrounding tissue. In contrast, cancer cells as single-cell eukaryotes live in a disrupted, heterogeneous environment with opportunities and hazards. Thus, cancer cells, unlike normal somatic cells, must constantly obtain information from their environment to ensure survival and proliferation. In this study, we build upon a simple mathematical modeling framework developed to predict (1) how information promotes population persistence in a highly heterogeneous environment and (2) how disruption of information resulting from habitat fragmentation increases the probability of population extinction. Because (1) tumors grow in a highly heterogeneous microenvironment and (2) many cancer therapies fragment tumors into isolated, small cancer cell populations, we identify parallels between these 2 systems and develop ideas for cancer cure based on lessons gleaned from Anthropocene extinctions. In many Anthropocene extinctions, such as that of the North American heath hen (Tympanuchus cupido cupido), a large and widespread population was initially reduced and fragmented owing to overexploitation by humans (a "first strike"). After this, the small surviving populations are vulnerable to extinction from environmental or demographic stochastic disturbances (a "second strike"). Following this analogy, after a tumor is fragmented into small populations of isolated cancer cells by an initial therapy, additional treatment can be applied with the intent of extinction (cure). Disrupting a cancer cell's ability to acquire and use information in a heterogeneous environment may be an important tactic for causing extinction following an effective initial therapy. Thus, information, from the scale of cells within tumors to that of species within ecosystems, can be used to identify vulnerabilities to extinction and opportunities for novel treatment strategies.}, } @article {pmid32738355, year = {2020}, author = {Miller, WB and Baluška, F and Torday, JS}, title = {Cellular senomic measurements in Cognition-Based Evolution.}, journal = {Progress in biophysics and molecular biology}, volume = {156}, number = {}, pages = {20-33}, doi = {10.1016/j.pbiomolbio.2020.07.002}, pmid = {32738355}, issn = {1873-1732}, mesh = {Animals ; *Biological Evolution ; Biology/trends ; Cell Communication ; *Cognition ; Homeostasis ; Humans ; Models, Biological ; Thermodynamics ; }, abstract = {All living entities are cognitive and dependent on ambiguous information. Any assessment of that imprecision is necessarily a measuring function. Individual cells measure information to sustain self-referential homeostatic equipoise (self-identity) in juxtaposition to the external environment. The validity of that information is improved by its collective assessment. The reception of cellular information obliges thermodynamic reactions that initiate a self-reinforcing work channel. This expresses as natural cellular engineering and niche constructions which become the complex interrelated tissue ecologies of holobionts. Multicellularity is collaborative cellular information management directed towards the optimization of information quality through its collective measured assessment. Biology and its evolution can now be re-framed as the continuous process of self-referential cellular measurement in the perpetual defense of individual cellular self-identities through the collective form.}, } @article {pmid32731489, year = {2020}, author = {Pajkos, M and Zeke, A and Dosztányi, Z}, title = {Ancient Evolutionary Origin of Intrinsically Disordered Cancer Risk Regions.}, journal = {Biomolecules}, volume = {10}, number = {8}, pages = {}, pmid = {32731489}, issn = {2218-273X}, support = {FIEK16-1-2016-0005//FIEK Grant of the National Research, Development and Innovation Office/International ; ED-18-1-2019-003//ELTE Thematic Excellence Programme supported by the Hungarian Ministry for Innovation and Technology./International ; }, mesh = {Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Evolution, Molecular ; Gene Duplication ; Humans ; Intrinsically Disordered Proteins/chemistry/*genetics ; Mutation ; Neoplasms/*genetics ; Protein Conformation ; Protein Domains ; }, abstract = {Cancer is a heterogeneous genetic disease that alters the proper functioning of proteins involved in key regulatory processes such as cell cycle, DNA repair, survival, or apoptosis. Mutations often accumulate in hot-spots regions, highlighting critical functional modules within these proteins that need to be altered, amplified, or abolished for tumor formation. Recent evidence suggests that these mutational hotspots can correspond not only to globular domains, but also to intrinsically disordered regions (IDRs), which play a significant role in a subset of cancer types. IDRs have distinct functional properties that originate from their inherent flexibility. Generally, they correspond to more recent evolutionary inventions and show larger sequence variations across species. In this work, we analyzed the evolutionary origin of disordered regions that are specifically targeted in cancer. Surprisingly, the majority of these disordered cancer risk regions showed remarkable conservation with ancient evolutionary origin, stemming from the earliest multicellular animals or even beyond. Nevertheless, we encountered several examples where the mutated region emerged at a later stage compared with the origin of the gene family. We also showed the cancer risk regions become quickly fixated after their emergence, but evolution continues to tinker with their genes with novel regulatory elements introduced even at the level of humans. Our concise analysis provides a much clearer picture of the emergence of key regulatory elements in proteins and highlights the importance of taking into account the modular organisation of proteins for the analyses of evolutionary origin.}, } @article {pmid32723540, year = {2020}, author = {Ovsepian, SV and O'Leary, VB and Vesselkin, NP}, title = {Evolutionary origins of chemical synapses.}, journal = {Vitamins and hormones}, volume = {114}, number = {}, pages = {1-21}, doi = {10.1016/bs.vh.2020.04.009}, pmid = {32723540}, issn = {0083-6729}, mesh = {Animals ; *Biological Evolution ; Neurons/*physiology ; Synapses/physiology ; Synaptic Transmission/*genetics/*physiology ; }, abstract = {Synaptic transmission is a fundamental neurobiological process by which neurons interact with each other and non-neuronal cells. It involves release of active substances from the presynaptic neuron onto receptive elements of postsynaptic cells, inducing waves of spreading electrochemical response. While much has been learned about the cellular and molecular mechanisms driving and governing transmitter release and sensing, the evolutionary origin of synaptic connections remains obscure. Herein, we review emerging evidence and concepts suggesting that key components of chemical synapse arose independently from neurons, in different functional and biological contexts, before the rise of multicellular living forms. We argue that throughout evolution, distinct synaptic constituents have been co-opted from ancestral forms for a new role in early metazoan, leading to the rise of chemical synapses and neurotransmission. Such a mosaic model of the origin of chemical synapses agrees with and supports the pluralistic hypothesis of evolutionary change.}, } @article {pmid32717856, year = {2020}, author = {Erber, L and Hoffmann, A and Fallmann, J and Hagedorn, M and Hammann, C and Stadler, PF and Betat, H and Prohaska, S and Mörl, M}, title = {Unusual Occurrence of Two Bona-Fide CCA-Adding Enzymes in Dictyostelium discoideum.}, journal = {International journal of molecular sciences}, volume = {21}, number = {15}, pages = {}, pmid = {32717856}, issn = {1422-0067}, mesh = {*Dictyostelium/enzymology/genetics ; *Genome, Protozoan ; *Protozoan Proteins/genetics/metabolism ; *RNA Nucleotidyltransferases/genetics/metabolism ; RNA, Protozoan/genetics/metabolism ; RNA, Transfer/genetics/metabolism ; }, abstract = {Dictyostelium discoideum, the model organism for the evolutionary supergroup of Amoebozoa, is a social amoeba that, upon starvation, undergoes transition from a unicellular to a multicellular organism. In its genome, we identified two genes encoding for tRNA nucleotidyltransferases. Such pairs of tRNA nucleotidyltransferases usually represent collaborating partial activities catalyzing CC- and A-addition to the tRNA 3'-end, respectively. In D. discoideum, however, both enzymes exhibit identical activities, representing bona-fide CCA-adding enzymes. Detailed characterization of the corresponding activities revealed that both enzymes seem to be essential and are regulated inversely during different developmental stages of D. discoideum. Intriguingly, this is the first description of two functionally equivalent CCA-adding enzymes using the same set of tRNAs and showing a similar distribution within the cell. This situation seems to be a common feature in Dictyostelia, as other members of this phylum carry similar pairs of tRNA nucleotidyltransferase genes in their genome.}, } @article {pmid32707067, year = {2020}, author = {Preussger, D and Giri, S and Muhsal, LK and Oña, L and Kost, C}, title = {Reciprocal Fitness Feedbacks Promote the Evolution of Mutualistic Cooperation.}, journal = {Current biology : CB}, volume = {30}, number = {18}, pages = {3580-3590.e7}, doi = {10.1016/j.cub.2020.06.100}, pmid = {32707067}, issn = {1879-0445}, mesh = {*Biological Evolution ; Escherichia coli/*genetics/growth & development/*metabolism ; *Feedback, Physiological ; *Genetic Fitness ; Humans ; *Microbial Interactions ; *Symbiosis ; }, abstract = {Mutually beneficial interactions are ubiquitous in nature and have played a pivotal role for the evolution of life on earth. However, the factors facilitating their emergence remain poorly understood. Here, we address this issue both experimentally and by mathematical modeling using cocultures of auxotrophic strains of Escherichia coli, whose growth depends on a reciprocal exchange of amino acids. Coevolving auxotrophic pairs in a spatially heterogeneous environment for less than 150 generations transformed the initial interaction that was merely based on an exchange of metabolic byproducts into a costly metabolic cooperation, in which both partners increased the amounts of metabolites they produced to benefit their corresponding partner. The observed changes were afforded by the formation of multicellular clusters, within which increased cooperative investments were favored by positive fitness feedbacks among interacting genotypes. Under these conditions, non-cooperative individuals were less fit than cooperative mutants. Together, our results highlight the ease with which mutualistic cooperation can evolve, suggesting similar mechanisms likely operate in natural communities. VIDEO ABSTRACT.}, } @article {pmid32698133, year = {2020}, author = {Yan, JJ and Lee, YC and Tsou, YL and Tseng, YC and Hwang, PP}, title = {Insulin-like growth factor 1 triggers salt secretion machinery in fish under acute salinity stress.}, journal = {The Journal of endocrinology}, volume = {246}, number = {3}, pages = {277-288}, doi = {10.1530/JOE-20-0053}, pmid = {32698133}, issn = {1479-6805}, mesh = {Animals ; Fish Proteins/metabolism ; Insulin-Like Growth Factor I/antagonists & inhibitors/*metabolism ; Oryzias ; Salinity ; Salt Stress ; Signal Transduction/drug effects ; Sodium Chloride/*pharmacology ; }, abstract = {Timely adjustment of osmoregulation upon acute salinity stress is essential for the survival of euryhaline fish. This rapid response is thought to be tightly controlled by hormones; however, there are still questions unanswered. In this work, we tested the hypothesis that the endocrine hormone, insulin-like growth factor 1 (Igf1), a slow-acting hormone, is involved in the activation of salt secretion mechanisms in euryhaline medaka (Oryzias melastigma) during acclimation to acute salinity stress. In response to a 30-ppt seawater (SW) challenge, Na+/Cl- secretion was enhanced within 0.5 h, with concomitant organization of ionocyte multicellular complexes and without changes in expression of major transporters. Igf1 receptor inhibitors significantly impair the Na+/Cl- secretion and ionocyte multicellular complex responses without affecting transporter expression. Thus, Igf1 may activate salt secretion as part of the teleost response to acute salinity stress by exerting effects on transporter function and enhancing the formation of ionocyte multicellular complexes. These findings provide new insights into hormonal control of body fluid ionic/osmotic homeostasis during vertebrate evolution.}, } @article {pmid32693719, year = {2020}, author = {Fisher, RM and Shik, JZ and Boomsma, JJ}, title = {The evolution of multicellular complexity: the role of relatedness and environmental constraints.}, journal = {Proceedings. Biological sciences}, volume = {287}, number = {1931}, pages = {20192963}, pmid = {32693719}, issn = {1471-2954}, mesh = {Animals ; *Biological Evolution ; Phylogeny ; }, abstract = {A major challenge in evolutionary biology has been to explain the variation in multicellularity across the many independently evolved multicellular lineages, from slime moulds to vertebrates. Social evolution theory has highlighted the key role of relatedness in determining multicellular complexity and obligateness; however, there is a need to extend this to a broader perspective incorporating the role of the environment. In this paper, we formally test Bonner's 1998 hypothesis that the environment is crucial in determining the course of multicellular evolution, with aggregative multicellularity evolving more frequently on land and clonal multicellularity more frequently in water. Using a combination of scaling theory and phylogenetic comparative analyses, we describe multicellular organizational complexity across 139 species spanning 14 independent transitions to multicellularity and investigate the role of the environment in determining multicellular group formation and in imposing constraints on multicellular evolution. Our results, showing that the physical environment has impacted the way in which multicellular groups form, highlight that environmental conditions might have affected the major evolutionary transition to obligate multicellularity.}, } @article {pmid32691527, year = {2020}, author = {Parmentier, T and De Laender, F and Bonte, D}, title = {The topology and drivers of ant-symbiont networks across Europe.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {95}, number = {6}, pages = {1664-1688}, doi = {10.1111/brv.12634}, pmid = {32691527}, issn = {1469-185X}, support = {BOF17/PDO/084//Bijzonder Onderzoeksfonds/International ; 1203020N//Fonds Wetenschappelijk Onderzoek/International ; W0.003.16N//Fonds Wetenschappelijk Onderzoek/International ; }, mesh = {Animals ; *Ants ; Biological Evolution ; Ecosystem ; Phylogeny ; Symbiosis ; }, abstract = {Intimate associations between different species drive community composition across ecosystems. Understanding the ecological and evolutionary drivers of these symbiotic associations is challenging because their structure eventually determines stability and resilience of the entire species network. Here, we compiled a detailed database on naturally occurring ant-symbiont networks in Europe to identify factors that affect symbiont network topology. These networks host an unrivalled diversity of macrosymbiotic associations, spanning the entire mutualism-antagonism continuum, including: (i) myrmecophiles - commensalistic and parasitic arthropods; (ii) trophobionts - mutualistic aphids, scale insects, planthoppers and caterpillars; (iii) social parasites - parasitic ant species; (iv) parasitic helminths; and (v) parasitic fungi. We dissected network topology to investigate what determines host specificity, symbiont species richness, and the capacity of different symbiont types to switch hosts. We found 722 macrosymbionts (multicellular symbionts) associated with European ants. Symbiont type explained host specificity and the average relatedness of the host species. Social parasites were associated with few hosts that were phylogenetically highly related, whereas the other symbiont types interacted with a larger number of hosts across a wider taxonomic distribution. The hosts of trophobionts were the least phylogenetically related across all symbiont types. Colony size, host range and habitat type predicted total symbiont richness: ant hosts with larger colony size, a larger distribution range or with a wider habitat range contained more symbiont species. However, we found that different sets of host factors affected diversity in the different types of symbionts. Ecological factors, such as colony size, host range and niche width predominantly determined myrmecophile species richness, whereas host phylogeny was the most important predictor of mutualistic trophobiont, social parasite and parasitic helminth species richness. Lastly, we found that hosts with a common biogeographic history support a more similar community of symbionts. Phylogenetically related hosts also shared more trophobionts, social parasites and helminths, but not myrmecophiles. Taken together, these results suggest that ecological and evolutionary processes structure host specificity and symbiont richness in large-scale ant-symbiont networks, but these drivers may shift in importance depending on the type of symbiosis. Our findings highlight the potential of well-characterized bipartite networks composed of different types of symbioses to identify candidate processes driving community composition.}, } @article {pmid32689913, year = {2020}, author = {Gonçalves, AP and Heller, J and Rico-Ramírez, AM and Daskalov, A and Rosenfield, G and Glass, NL}, title = {Conflict, Competition, and Cooperation Regulate Social Interactions in Filamentous Fungi.}, journal = {Annual review of microbiology}, volume = {74}, number = {}, pages = {693-712}, doi = {10.1146/annurev-micro-012420-080905}, pmid = {32689913}, issn = {1545-3251}, mesh = {Alleles ; Apoptosis ; Evolution, Molecular ; Fungal Proteins/*genetics/metabolism ; Fungi/classification/*genetics ; *Gene Expression Regulation, Fungal ; Haplotypes ; Microbial Interactions/*genetics/physiology ; Phylogeny ; }, abstract = {Social cooperation impacts the development and survival of species. In higher taxa, kin recognition occurs via visual, chemical, or tactile cues that dictate cooperative versus competitive interactions. In microbes, the outcome of cooperative versus competitive interactions is conferred by identity at allorecognition loci, so-called kind recognition. In syncytial filamentous fungi, the acquisition of multicellularity is associated with somatic cell fusion within and between colonies. However, such intraspecific cooperation entails risks, as fusion can transmit deleterious genotypes or infectious components that reduce fitness, or give rise to cheaters that can exploit communal goods without contributing to their production. Allorecognition mechanisms in syncytial fungi regulate somatic cell fusion by operating precontact during chemotropic interactions, during cell adherence, and postfusion by triggering programmed cell death reactions. Alleles at fungal allorecognition loci are highly polymorphic, fall into distinct haplogroups, and show evolutionary signatures of balancing selection, similar to allorecognition loci across the tree of life.}, } @article {pmid32687894, year = {2020}, author = {Wavreil, FDM and Yajima, M}, title = {Diversity of activator of G-protein signaling (AGS)-family proteins and their impact on asymmetric cell division across taxa.}, journal = {Developmental biology}, volume = {465}, number = {2}, pages = {89-99}, pmid = {32687894}, issn = {1095-564X}, support = {R01 GM126043/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Asymmetric Cell Division/*physiology ; Cell Cycle Proteins/genetics/*metabolism ; Humans ; *Multigene Family ; Signal Transduction/*physiology ; Species Specificity ; Spindle Apparatus/genetics/*metabolism ; }, abstract = {Asymmetric cell division (ACD) is a cellular process that forms two different cell types through a cell division and is thus critical for the development of all multicellular organisms. Not all but many of the ACD processes are mediated by proper orientation of the mitotic spindle, which segregates the fate determinants asymmetrically into daughter cells. In many cell types, the evolutionarily conserved protein complex of Gαi/AGS-family protein/NuMA-like protein appears to play critical roles in orienting the spindle and/or generating the polarized cortical forces to regulate ACD. Studies in various organisms reveal that this conserved protein complex is slightly modified in each phylum or even within species. In particular, AGS-family proteins appear to be modified with a variable number of motifs in their functional domains across taxa. This apparently creates different molecular interactions and mechanisms of ACD in each developmental program, ultimately contributing to developmental diversity across species. In this review, we discuss how a conserved ACD machinery has been modified in each phylum over the course of evolution with a major focus on the molecular evolution of AGS-family proteins and its impact on ACD regulation.}, } @article {pmid32681710, year = {2021}, author = {Rose, CJ}, title = {Germ lines and extended selection during the evolutionary transition to multicellularity.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {336}, number = {8}, pages = {680-686}, doi = {10.1002/jez.b.22985}, pmid = {32681710}, issn = {1552-5015}, mesh = {Animals ; *Biological Evolution ; *Germ Cells ; Life Cycle Stages ; Reproduction ; *Selection, Genetic ; }, abstract = {The major evolutionary transitions from unicellular organisms to multicellularity resulted in a profusion of complex life forms. During the transition from single cells to multicellular life, groups of cells acquired the capacity for reproduction as discrete units; however, the selective causes and underlying mechanisms remain debated. One perspective views the evolution of multicellularity as a shift in the timescale at which natural selection primarily operates-from that of individual cells to the timescale of reproducing groups of cells. Therefore, a distinguishing feature of multicellular reproduction, as opposed to simple growth of a multicellular collective, is that the capacity for reproduction must develop over a timescale that is greater than the reproductive timescale of a single cell. Here, I suggest that the emergence of specialized reproductive cells (the germ line) was an essential first stage of the evolutionary transition to multicellularity because it imposed the necessary "delay"-allowing natural selection to operate over the longer timescale of a multicellular life cycle, ultimately resulting in the evolution of complex multicellular organisms. This perspective highlights the possibility that the ubiquity of a germ-soma distinction among complex multicellular organisms reflects the fact that such life cycles, on first emergence, had the greatest propensity to participate in Darwinian evolution.}, } @article {pmid32677677, year = {2020}, author = {Nedelcu, AM}, title = {The evolution of multicellularity and cancer: views and paradigms.}, journal = {Biochemical Society transactions}, volume = {48}, number = {4}, pages = {1505-1518}, doi = {10.1042/BST20190992}, pmid = {32677677}, issn = {1470-8752}, mesh = {*Biological Evolution ; Humans ; Models, Biological ; Neoplasms/metabolism/*pathology ; Spheroids, Cellular/*metabolism ; Tumor Microenvironment ; }, abstract = {Conceptually and mechanistically, the evolution of multicellularity required the integration of single cells into new functionally, reproductively and evolutionary stable multicellular individuals. As part of this process, a change in levels of selection occurred, with selection at the multicellular level overriding selection at the cell level. The stability of multicellular individuals is dependent on a combination of mechanisms that supress within-group evolution, by both reducing the occurrence of somatic mutations as well as supressing somatic selection. Nevertheless, mutations that, in a particular microenvironment, confer mutant lineages a fitness advantage relative to normal somatic cells do occur, and can result in cancer. This minireview highlights several views and paradigms that relate the evolution of multicellularity to cancer. As a phenomenon, cancer is generally understood as a failure of multicellular systems to suppress somatic evolution. However, as a disease, cancer is interpreted in different frameworks: (i) a breakdown of cooperative behaviors underlying the evolution of multicellularity, (ii) a disruption of molecular networks established during the emergence of multicellularity to impose constraints on single-celled units, or (iii) an atavistic state resulting from reactivating primitive programs that originated in the earliest unicellular species. A number of assumptions are common in all the views relating cancer as a disease to the evolution of multicellularity. For instance, cancer is considered a reversal to unicellularity, and cancer cells are thought to both resemble unicellular organisms and benefit from ancestral-like traits. Nevertheless, potential limitations of current paradigms should be acknowledged as different perspectives can provide novel insights with potential therapeutic implications.}, } @article {pmid32664620, year = {2020}, author = {Bylino, OV and Ibragimov, AN and Shidlovskii, YV}, title = {Evolution of Regulated Transcription.}, journal = {Cells}, volume = {9}, number = {7}, pages = {}, pmid = {32664620}, issn = {2073-4409}, mesh = {Animals ; Enhancer Elements, Genetic ; *Evolution, Molecular ; *Gene Expression Regulation ; Genome Size ; Humans ; Models, Genetic ; *Transcription, Genetic ; }, abstract = {The genomes of all organisms abound with various cis-regulatory elements, which control gene activity. Transcriptional enhancers are a key group of such elements in eukaryotes and are DNA regions that form physical contacts with gene promoters and precisely orchestrate gene expression programs. Here, we follow gradual evolution of this regulatory system and discuss its features in different organisms. In eubacteria, an enhancer-like element is often a single regulatory element, is usually proximal to the core promoter, and is occupied by one or a few activators. Activation of gene expression in archaea is accompanied by the recruitment of an activator to several enhancer-like sites in the upstream promoter region. In eukaryotes, activation of expression is accompanied by the recruitment of activators to multiple enhancers, which may be distant from the core promoter, and the activators act through coactivators. The role of the general DNA architecture in transcription control increases in evolution. As a whole, it can be seen that enhancers of multicellular eukaryotes evolved from the corresponding prototypic enhancer-like regulatory elements with the gradually increasing genome size of organisms.}, } @article {pmid32659023, year = {2020}, author = {Begum, R and Saran, S}, title = {Glimpses of Dictyostelid research in India.}, journal = {The International journal of developmental biology}, volume = {64}, number = {1-2-3}, pages = {99-107}, doi = {10.1387/ijdb.190208ss}, pmid = {32659023}, issn = {1696-3547}, mesh = {Animals ; *Biological Evolution ; Biomedical Research/*trends ; Cell Differentiation ; Dictyostelium/*physiology ; *Gene Expression Regulation ; India ; Models, Biological ; *Morphogenesis ; }, abstract = {Simple organisms are preferred for understanding the molecular and cellular function(s) of complex processes. Dictyostelium discoideum is a lower eukaryote, a protist and a cellular slime mould, which has been in recent times used for various studies such as cell differentiation, development, cell death, stress responses etc. It is a soil amoeba (unicellular) that undertakes a remarkable, facultative shift to multicellularity when exposed to starvation and requires signal pathways that result in alteration of gene expression and finally show cell differentiation. The amoebae aggregate, differentiate and form fruiting bodies with two terminally differentiated cells: the dead stalk (non-viable) and dormant spores (viable). In India, starting from the isolation of Dictyostelium species to morphogenesis, cell signalling and social evolution has been studied with many more new research additions. Advances in molecular genetics make Dictyostelium an attractive model system to study cell biology, biochemistry, signal transduction and many more.}, } @article {pmid32658971, year = {2020}, author = {Helsen, J and Voordeckers, K and Vanderwaeren, L and Santermans, T and Tsontaki, M and Verstrepen, KJ and Jelier, R}, title = {Gene Loss Predictably Drives Evolutionary Adaptation.}, journal = {Molecular biology and evolution}, volume = {37}, number = {10}, pages = {2989-3002}, pmid = {32658971}, issn = {1537-1719}, mesh = {Adaptation, Biological/*genetics ; *Biological Evolution ; *Gene Deletion ; Gene Regulatory Networks ; *Genetic Fitness ; Oxidative Stress/genetics ; Saccharomyces cerevisiae ; }, abstract = {Loss of gene function is common throughout evolution, even though it often leads to reduced fitness. In this study, we systematically evaluated how an organism adapts after deleting genes that are important for growth under oxidative stress. By evolving, sequencing, and phenotyping over 200 yeast lineages, we found that gene loss can enhance an organism's capacity to evolve and adapt. Although gene loss often led to an immediate decrease in fitness, many mutants rapidly acquired suppressor mutations that restored fitness. Depending on the strain's genotype, some ultimately even attained higher fitness levels than similarly adapted wild-type cells. Further, cells with deletions in different modules of the genetic network followed distinct and predictable mutational trajectories. Finally, losing highly connected genes increased evolvability by facilitating the emergence of a more diverse array of phenotypes after adaptation. Together, our findings show that loss of specific parts of a genetic network can facilitate adaptation by opening alternative evolutionary paths.}, } @article {pmid32653903, year = {2020}, author = {Plachetzki, DC and Pankey, MS and MacManes, MD and Lesser, MP and Walker, CW}, title = {The Genome of the Softshell Clam Mya arenaria and the Evolution of Apoptosis.}, journal = {Genome biology and evolution}, volume = {12}, number = {10}, pages = {1681-1693}, pmid = {32653903}, issn = {1759-6653}, support = {R15 CA104112/CA/NCI NIH HHS/United States ; R35 GM128843/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Apoptosis/*genetics ; *Genes, p53 ; *Genome ; Mya/*genetics ; *Phylogeny ; }, abstract = {Apoptosis is a fundamental feature of multicellular animals and is best understood in mammals, flies, and nematodes, with the invertebrate models being thought to represent a condition of ancestral simplicity. However, the existence of a leukemia-like cancer in the softshell clam Mya arenaria provides an opportunity to re-evaluate the evolution of the genetic machinery of apoptosis. Here, we report the whole-genome sequence for M. arenaria which we leverage with existing data to test evolutionary hypotheses on the origins of apoptosis in animals. We show that the ancestral bilaterian p53 locus, a master regulator of apoptosis, possessed a complex domain structure, in contrast to that of extant ecdysozoan p53s. Further, ecdysozoan taxa, but not chordates or lophotrochozoans like M. arenaria, show a widespread reduction in apoptosis gene copy number. Finally, phylogenetic exploration of apoptosis gene copy number reveals a striking linkage with p53 domain complexity across species. Our results challenge the current understanding of the evolution of apoptosis and highlight the ancestral complexity of the bilaterian apoptotic tool kit and its subsequent dismantlement during the ecdysozoan radiation.}, } @article {pmid32651001, year = {2021}, author = {Picard, M and Sandi, C}, title = {The social nature of mitochondria: Implications for human health.}, journal = {Neuroscience and biobehavioral reviews}, volume = {120}, number = {}, pages = {595-610}, pmid = {32651001}, issn = {1873-7528}, support = {R01 MH119336/MH/NIMH NIH HHS/United States ; R01 MH122706/MH/NIMH NIH HHS/United States ; R35 GM119793/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; Humans ; *Mitochondria ; Social Behavior ; }, abstract = {Sociality has profound evolutionary roots and is observed from unicellular organisms to multicellular animals. In line with the view that social principles apply across levels of biological complexity, a growing body of data highlights the remarkable social nature of mitochondria - life-sustaining endosymbiotic organelles with their own genome that populate the cell cytoplasm. Here, we draw from organizing principles of behavior in social organisms to reveal that similar to individuals among social networks, mitochondria communicate with each other and with the cell nucleus, exhibit group formation and interdependence, synchronize their behaviors, and functionally specialize to accomplish specific functions within the organism. Mitochondria are social organelles. The extension of social principles across levels of biological complexity is a theoretical shift that emphasizes the role of communication and interdependence in cell biology, physiology, and neuroscience. With the help of emerging computational methods capable of capturing complex dynamic behavioral patterns, the implementation of social concepts in mitochondrial biology may facilitate cross-talk across disciplines towards increasingly holistic and accurate models of human health.}, } @article {pmid32649861, year = {2020}, author = {Brunkard, JO}, title = {Exaptive Evolution of Target of Rapamycin Signaling in Multicellular Eukaryotes.}, journal = {Developmental cell}, volume = {54}, number = {2}, pages = {142-155}, pmid = {32649861}, issn = {1878-1551}, support = {DP5 OD023072/OD/NIH HHS/United States ; }, mesh = {Amino Acids/metabolism ; Animals ; Eukaryota/*drug effects/metabolism ; Signal Transduction/*drug effects/physiology ; Sirolimus/*pharmacology ; TOR Serine-Threonine Kinases/*metabolism ; }, abstract = {Target of rapamycin (TOR) is a protein kinase that coordinates metabolism with nutrient and energy availability in eukaryotes. TOR and its primary interactors, RAPTOR and LST8, have been remarkably evolutionarily static since they arose in the unicellular last common ancestor of plants, fungi, and animals, but the upstream regulatory mechanisms and downstream effectors of TOR signaling have evolved considerable diversity in these separate lineages. Here, I focus on the roles of exaptation and adaptation in the evolution of novel signaling axes in the TOR network in multicellular eukaryotes, concentrating especially on amino acid sensing, cell-cell signaling, and cell differentiation.}, } @article {pmid32643307, year = {2020}, author = {Rose, CJ and Hammerschmidt, K and Pichugin, Y and Rainey, PB}, title = {Meta-population structure and the evolutionary transition to multicellularity.}, journal = {Ecology letters}, volume = {23}, number = {9}, pages = {1380-1390}, doi = {10.1111/ele.13570}, pmid = {32643307}, issn = {1461-0248}, mesh = {Animals ; *Biological Evolution ; Life Cycle Stages ; Phenotype ; *Reproduction ; }, abstract = {The evolutionary transition to multicellularity has occurred on numerous occasions, but transitions to complex life forms are rare. Here, using experimental bacterial populations as proxies for nascent multicellular organisms, we manipulate ecological factors shaping the evolution of groups. Groups were propagated under regimes requiring reproduction via a life cycle replete with developmental and dispersal (propagule) phases, but in one treatment lineages never mixed, whereas in a second treatment, cells from different lineages experienced intense competition during the dispersal phase. The latter treatment favoured traits promoting cell growth at the expense of traits underlying group fitness - a finding that is supported by results from a mathematical model. Our results show that the transition to multicellularity benefits from ecological conditions that maintain discreteness not just of the group (soma) phase, but also of the dispersal (germline) phase.}, } @article {pmid32626570, year = {2020}, author = {Umen, JG}, title = {Volvox and volvocine green algae.}, journal = {EvoDevo}, volume = {11}, number = {}, pages = {13}, pmid = {32626570}, issn = {2041-9139}, abstract = {The transition of life from single cells to more complex multicellular forms has occurred at least two dozen times among eukaryotes and is one of the major evolutionary transitions, but the early steps that enabled multicellular life to evolve and thrive remain poorly understood. Volvocine green algae are a taxonomic group that is uniquely suited to investigating the step-wise acquisition of multicellular organization. The multicellular volvocine species Volvox carteri exhibits many hallmarks of complex multicellularity including complete germ-soma division of labor, asymmetric cell divisions, coordinated tissue-level morphogenesis, and dimorphic sexes-none of which have obvious analogs in its closest unicellular relative, the model alga Chlamydomonas reinhardtii. Here, I summarize some of the key questions and areas of study that are being addressed with Volvox carteri and how increasing genomic information and methodologies for volvocine algae are opening up the entire group as an integrated experimental system for exploring the evolution of multicellularity and more.}, } @article {pmid32617614, year = {2020}, author = {Seoighe, C and Kiniry, SJ and Peters, A and Baranov, PV and Yang, H}, title = {Selection Shapes Synonymous Stop Codon Use in Mammals.}, journal = {Journal of molecular evolution}, volume = {88}, number = {7}, pages = {549-561}, doi = {10.1007/s00239-020-09957-x}, pmid = {32617614}, issn = {1432-1432}, support = {210692/Z/18/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; *Codon, Terminator ; *Evolution, Molecular ; Humans ; Mammals/*genetics ; *Models, Genetic ; Phylogeny ; }, abstract = {Phylogenetic models of the evolution of protein-coding sequences can provide insights into the selection pressures that have shaped them. In the application of these models synonymous nucleotide substitutions, which do not alter the encoded amino acid, are often assumed to have limited functional consequences and used as a proxy for the neutral rate of evolution. The ratio of nonsynonymous to synonymous substitution rates is then used to categorize the selective regime that applies to the protein (e.g., purifying selection, neutral evolution, diversifying selection). Here, we extend the Muse and Gaut model of codon evolution to explore the extent of purifying selection acting on substitutions between synonymous stop codons. Using a large collection of coding sequence alignments, we estimate that a high proportion (approximately 57%) of mammalian genes are affected by selection acting on stop codon preference. This proportion varies substantially by codon, with UGA stop codons far more likely to be conserved. Genes with evidence of selection acting on synonymous stop codons have distinctive characteristics, compared to unconserved genes with the same stop codon, including longer [Formula: see text] untranslated regions (UTRs) and shorter mRNA half-life. The coding regions of these genes are also much more likely to be under strong purifying selection pressure. Our results suggest that the preference for UGA stop codons found in many multicellular eukaryotes is selective rather than mutational in origin.}, } @article {pmid32603492, year = {2020}, author = {Liao, X and Wang, J and Zhu, S and Xie, Q and Wang, L and Yu, H and Ye, Z and Yang, C}, title = {Transcriptomic and functional analyses uncover the regulatory role of lncRNA000170 in tomato multicellular trichome formation.}, journal = {The Plant journal : for cell and molecular biology}, volume = {104}, number = {1}, pages = {18-29}, doi = {10.1111/tpj.14902}, pmid = {32603492}, issn = {1365-313X}, mesh = {Gene Expression Profiling ; Solanum lycopersicum/growth & development/*metabolism ; MicroRNAs/metabolism/physiology ; RNA, Long Noncoding/metabolism/*physiology ; RNA, Plant/metabolism/*physiology ; Trichomes/*genetics/metabolism ; }, abstract = {Trichomes are universal specific structures originating from nearly all terrestrial plants. Although quantities of long non-coding RNAs (lncRNAs) have been identified in many plant species, the role of lncRNAs in trichome formation still remains unknown. Here, we identified a total of 1303 lncRNAs in the young stems of woolly mutant LA3560 (Wo) and its non-woolly segregants (WT). Out of these lncRNAs, 86 lncRNAs were obviously upregulated in Wo and 110 lncRNAs were downregulated. We determined that seven lncRNAs were highly expressed in stem trichomes compared to trichome-free stems and several other tissues of LA3560 by a quantitative reverse transcriptase-polymerase chain reaction, including lncRNA000746, lncRNA000170, lncRNA000277, lncRNA000774, lncRNA000756, lncRNA000100, and lncRNA000898. Transgenic experiments revealed that overexpression of lncRNA000170 inhibited type I trichome formation on the lower stems of the adult transgenic plants. We further determined that lncRNA000170 was transcribed from the complementary strand of Solyc10g006360, for which expression can be induced by lncRNA000170 in its overexpression lines and woolly mutants. Solyc10g006360 overexpression also caused type I trichome decrease. In addition, several trichome regulators, such as Wo, H, SlCycB2, and SlCycB3, were markedly downregulated in lncRNA000170 overexpression lines. These findings demonstrate that lncRNA000170 may be involved in the regulatory pathway mediated by these trichome regulators.}, } @article {pmid32602227, year = {2020}, author = {Ryu, C and Walia, A and Ortiz, V and Perry, C and Woo, S and Reeves, BC and Sun, H and Winkler, J and Kanyo, JE and Wang, W and Vukmirovic, M and Ristic, N and Stratton, EA and Meena, SR and Minasyan, M and Kurbanov, D and Liu, X and Lam, TT and Farina, G and Gomez, JL and Gulati, M and Herzog, EL}, title = {Bioactive Plasma Mitochondrial DNA Is Associated With Disease Progression in Scleroderma-Associated Interstitial Lung Disease.}, journal = {Arthritis & rheumatology (Hoboken, N.J.)}, volume = {72}, number = {11}, pages = {1905-1915}, pmid = {32602227}, issn = {2326-5205}, support = {U01HL112702/HL/NHLBI NIH HHS/United States ; S10-OD-018034-01/HL/NHLBI NIH HHS/United States ; R01 HL152677/HL/NHLBI NIH HHS/United States ; K01-HL1-25474-03/HL/NHLBI NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; R01 HL109233/HL/NHLBI NIH HHS/United States ; U01 HL112702/HL/NHLBI NIH HHS/United States ; R01-HL-109233/HL/NHLBI NIH HHS/United States ; R01-HL-125850/HL/NHLBI NIH HHS/United States ; K08 HL151970/HL/NHLBI NIH HHS/United States ; R01 HL153604/HL/NHLBI NIH HHS/United States ; R03 HL154275/HL/NHLBI NIH HHS/United States ; K01 HL125474/HL/NHLBI NIH HHS/United States ; R01 HL125850/HL/NHLBI NIH HHS/United States ; U01-HL-112702/HL/NHLBI NIH HHS/United States ; }, mesh = {Actins/metabolism ; Cytokines/metabolism ; DNA, Mitochondrial/*blood ; Disease Progression ; Female ; Fibroblasts/metabolism ; HEK293 Cells ; Humans ; Lung Diseases, Interstitial/*blood/etiology ; Male ; Scleroderma, Systemic/*blood/complications ; }, abstract = {OBJECTIVE: Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is characterized by variable clinical outcomes, activation of innate immune pattern-recognition receptors (PRRs), and accumulation of α-smooth muscle actin (α-SMA)-expressing myofibroblasts. The aim of this study was to identify an association between these entities and mitochondrial DNA (mtDNA), an endogenous ligand for the intracellular DNA-sensing PRRs Toll-like receptor 9 (TLR-9) and cyclic GMP-AMP synthase/stimulator of interferon genes (cGAS/STING), which has yet to be determined.

METHODS: Human lung fibroblasts (HLFs) from normal donors and SSc-ILD explants were treated with synthetic CpG DNA and assayed for α-SMA expression and extracellular mtDNA using quantitative polymerase chain reaction for the human MT-ATP6 gene. Plasma MT-ATP6 concentrations were evaluated in 2 independent SSc-ILD cohorts and demographically matched controls. The ability of SSc-ILD and control plasma to induce TLR-9 and cGAS/STING activation was evaluated with commercially available HEK 293 reporter cells. Plasma concentrations of type I interferons (IFNs), interleukin-6 (IL-6), and oxidized DNA were measured using electrochemiluminescence and enzyme-linked immunosorbent assay-based methods. Extracellular vesicles (EVs) precipitated from plasma were evaluated for MT-ATP6 concentrations and proteomics via liquid chromatography mass spectrometry.

RESULTS: Normal HLFs and SSc-ILD fibroblasts developed increased α-SMA expression and MT-ATP6 release following CpG stimulation. Plasma mtDNA concentrations were increased in the 2 SSc-ILD cohorts, reflective of ventilatory decline, and were positively associated with both TLR-9 and cGAS/STING activation as well as type I IFN and IL-6 expression. Plasma mtDNA was not oxidized and was conveyed by EVs displaying a proteomics profile consistent with a multicellular origin.

CONCLUSION: These findings demonstrate a previously unrecognized connection between EV-encapsulated mtDNA, clinical outcomes, and intracellular DNA-sensing PRR activation in SSc-ILD. Further study of these interactions could catalyze novel mechanistic and therapeutic insights into SSc-ILD and related disorders.}, } @article {pmid32599749, year = {2020}, author = {Opalek, M and Wloch-Salamon, D}, title = {Aspects of Multicellularity in Saccharomyces cerevisiae Yeast: A Review of Evolutionary and Physiological Mechanisms.}, journal = {Genes}, volume = {11}, number = {6}, pages = {}, pmid = {32599749}, issn = {2073-4425}, mesh = {*Biological Evolution ; Phenotype ; Saccharomyces cerevisiae/*genetics ; }, abstract = {The evolutionary transition from single-celled to multicellular growth is a classic and intriguing problem in biology. Saccharomyces cerevisiae is a useful model to study questions regarding cell aggregation, heterogeneity and cooperation. In this review, we discuss scenarios of group formation and how this promotes facultative multicellularity in S. cerevisiae. We first describe proximate mechanisms leading to aggregation. These mechanisms include staying together and coming together, and can lead to group heterogeneity. Heterogeneity is promoted by nutrient limitation, structured environments and aging. We then characterize the evolutionary benefits and costs of facultative multicellularity in yeast. We summarize current knowledge and focus on the newest state-of-the-art discoveries that will fuel future research programmes aiming to understand facultative microbial multicellularity.}, } @article {pmid32592586, year = {2020}, author = {Lustofin, K and Świątek, P and Stolarczyk, P and Miranda, VFO and Płachno, BJ}, title = {Do food trichomes occur in Pinguicula (Lentibulariaceae) flowers?.}, journal = {Annals of botany}, volume = {126}, number = {6}, pages = {1039-1048}, pmid = {32592586}, issn = {1095-8290}, mesh = {Animals ; Bees ; *Flowers ; Phylogeny ; Pollination ; South America ; *Trichomes ; }, abstract = {BACKGROUND AND AIMS: Floral food bodies (including edible trichomes) are a form of floral reward for pollinators. This type of nutritive reward has been recorded in several angiosperm families: Annonaceae, Araceae, Calycanthaceae, Eupomatiaceae, Himantandraceae, Nymphaeaceae, Orchidaceae, Pandanaceae and Winteraceae. Although these bodies are very diverse in their structure, their cells contain food material: starch grains, protein bodies or lipid droplets. In Pinguicula flowers, there are numerous multicellular clavate trichomes. Previous authors have proposed that these trichomes in the Pinguicula flower play the role of 'futterhaare' ('feeding hairs') and are eaten by pollinators. The main aim of this study was to investigate whether the floral non-glandular trichomes of Pinguicula contain food reserves and thus are a reward for pollinators. The trichomes from the Pinguicula groups, which differ in their taxonomy (species from the subgenera: Temnoceras, Pinguicula and Isoloba) as well as the types of their pollinators (butterflies/flies and bees/hummingbirds), were examined. Thus, it was determined whether there are any connections between the occurrence of food trichomes and phylogeny position or pollination biology. Additionally, we determined the phylogenetic history of edible trichomes and pollinator evolution in the Pinguicula species.

METHODS: The species that were sampled were: Pinguicula moctezumae, P. esseriana, P. moranensis, P. emarginata, P. rectifolia, P. mesophytica, P. hemiepiphytica, P. agnata, P. albida, P. ibarrae, P. martinezii, P. filifolia, P. gigantea, P. lusitanica, P. alpina and P. vulgaris. Light microscopy, histochemistry, and scanning and transmission electron microscopy were used to address our aims with a phylogenetic perspective based on matK/trnK DNA sequences.

KEY RESULTS: No accumulation of protein bodies or lipid droplets was recorded in the floral non-glandular trichomes of any of the analysed species. Starch grains occurred in the cells of the trichomes of the bee-/fly-pollinated species: P. agnata, P. albida, P. ibarrae, P. martinezii, P. filifolia and P. gigantea, but not in P. alpina or P. vulgaris. Moreover, starch grains were not recorded in the cells of the trichomes of the Pinguicula species that have long spurs, which are pollinated by Lepidoptera (P. moctezumae, P. esseriana, P. moranensis, P. emarginata and P. rectifolia) or birds (P. mesophytica and P. hemiepihytica), or in species with a small and whitish corolla that self-pollinate (P. lusitanica). The results on the occurrence of edible trichomes and pollinator syndromes were mapped onto a phylogenetic reconstruction of the genus.

CONCLUSION: Floral non-glandular trichomes play the role of edible trichomes in some Pinguicula species (P. agnata, P. albida, P. ibarrae, P. martinezii, P. filifolia and P. gigantea), which are mainly classified as bee-pollinated species that had originated from Central and South America. It seems that in the Pinguicula that are pollinated by other pollinator groups (Lepidoptera and hummingbirds), the non-glandular trichomes in the flowers play a role other than that of a floral reward for their pollinators. Edible trichomes are symplesiomorphic for the Pinguicula species, and thus do not support a monophyletic group such as a synapomorphy. Nevertheless, edible trichomes are derived and are possibly a specialization for fly and bee pollinators by acting as a food reward for these visitors.}, } @article {pmid32572049, year = {2020}, author = {Jacqueline, C and Parvy, JP and Rollin, ML and Faugère, D and Renaud, F and Missé, D and Thomas, F and Roche, B}, title = {The role of innate immunity in the protection conferred by a bacterial infection against cancer: study of an invertebrate model.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {10106}, pmid = {32572049}, issn = {2045-2322}, support = {C596/A17196/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Animals ; Anti-Bacterial Agents/metabolism ; Antimicrobial Cationic Peptides/*metabolism ; Bacteria/genetics ; Bacterial Infections/metabolism ; Drosophila Proteins/metabolism/pharmacology ; Drosophila melanogaster ; Fungi/genetics ; Gene Expression/genetics ; Immunity, Innate/*physiology ; Invertebrates/genetics ; Larva/metabolism/microbiology ; Neoplasms/*immunology/prevention & control ; }, abstract = {All multicellular organisms are exposed to a diversity of infectious agents and to the emergence and proliferation of malignant cells. The protection conferred by some infections against cancer has been recently linked to the production of acquired immunity effectors such as antibodies. However, the evolution of innate immunity as a mechanism to prevent cancer and how it is jeopardized by infections remain poorly investigated. Here, we explored this question by performing experimental infections in two genetically modified invertebrate models (Drosophila melanogaster) that develop invasive or non-invasive neoplastic brain tumors. After quantifying tumor size and antimicrobial peptide gene expression, we found that Drosophila larvae infected with a naturally occurring bacterium had smaller tumors compared to controls and to fungus-infected larvae. This was associated with the upregulation of genes encoding two antimicrobial peptides-diptericin and drosomycin-that are known to be important mediators of tumor cell death. We further confirmed that tumor regression upon infection was associated with an increase in tumor cell death. Thus, our study suggests that infection could have a protective role through the production of antimicrobial peptides that increase tumor cell death. Finally, our study highlights the need to understand the role of innate immune effectors in the complex interactions between infections and cancer cell communities in order to develop innovative cancer treatment strategies.}, } @article {pmid32562277, year = {2021}, author = {Merle, NS and Singh, P and Rahman, J and Kemper, C}, title = {Integrins meet complement: The evolutionary tip of an iceberg orchestrating metabolism and immunity.}, journal = {British journal of pharmacology}, volume = {178}, number = {14}, pages = {2754-2770}, pmid = {32562277}, issn = {1476-5381}, mesh = {*Complement System Proteins ; Humans ; Immune System ; *Integrins ; }, abstract = {Immunologists have recently realized that there is more to the classic innate immune sensor systems than just mere protection against invading pathogens. It is becoming increasingly clear that such sensors, including the inflammasomes, toll-like receptors, and the complement system, are heavily involved in the regulation of basic cell physiological processes and particularly those of metabolic nature. In fact, their "non-canonical" activities make sense as no system directing immune cell activity can perform such task without the need for energy. Further, many of these ancient immune sensors appeared early and concurrently during evolution, particularly during the developmental leap from the single-cell organisms to multicellularity, and therefore crosstalk heavily with each other. Here, we will review the current knowledge about the emerging cooperation between the major inter-cell communicators, integrins, and the cell-autonomous intracellularly and autocrine-active complement, the complosome, during the regulation of single-cell metabolism. LINKED ARTICLES: This article is part of a themed issue on Canonical and non-canonical functions of the complement system in health and disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.14/issuetoc.}, } @article {pmid32535731, year = {2020}, author = {Hammarlund, EU and Amend, SR and Pienta, KJ}, title = {The issues with tissues: the wide range of cell fate separation enables the evolution of multicellularity and cancer.}, journal = {Medical oncology (Northwood, London, England)}, volume = {37}, number = {7}, pages = {62}, pmid = {32535731}, issn = {1559-131X}, mesh = {Animals ; Biological Evolution ; Cell Differentiation/physiology ; Cell Plasticity/physiology ; Cell Survival/physiology ; Ecosystem ; Humans ; Neoplasms/genetics/metabolism/*pathology ; Selection, Genetic ; }, abstract = {Our understanding of the rises of animal and cancer multicellularity face the same conceptual hurdles: what makes the clade originate and what makes it diversify. Between the events of origination and diversification lies complex tissue organization that gave rise to novel functionality for organisms and, unfortunately, for malignant transformation in cells. Tissue specialization with distinctly separated cell fates allowed novel functionality at organism level, such as for vertebrate animals, but also involved trade-offs at the cellular level that are potentially disruptive. These trade-offs are under-appreciated and here we discuss how the wide separation of cell phenotypes may contribute to cancer evolution by (a) how factors can reverse differentiated cells into a window of phenotypic plasticity, (b) the reversal to phenotypic plasticity coupled with asexual reproduction occurs in a way that the host cannot adapt, and (c) the power of the transformation factor correlates to the power needed to reverse tissue specialization. The role of reversed cell fate separation for cancer evolution is strengthened by how some tissues and organisms maintain high cell proliferation and plasticity without developing tumours at a corresponding rate. This demonstrates a potential proliferation paradox that requires further explanation. These insights from the cancer field, which observes tissue evolution in real time and closer than any other field, allow inferences to be made on evolutionary events in animal history. If a sweet spot of phenotypic and reproductive versatility is key to transformation, factors stimulating cell fate separation may have promoted also animal diversification on Earth.}, } @article {pmid32529251, year = {2020}, author = {Buschmann, H and Holzinger, A}, title = {Understanding the algae to land plant transition.}, journal = {Journal of experimental botany}, volume = {71}, number = {11}, pages = {3241-3246}, doi = {10.1093/jxb/eraa196}, pmid = {32529251}, issn = {1460-2431}, mesh = {*Embryophyta ; Evolution, Molecular ; Phylogeny ; *Plants ; }, } @article {pmid32523039, year = {2020}, author = {Duraivelan, K and Samanta, D}, title = {Tracing the evolution of nectin and nectin-like cell adhesion molecules.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {9434}, pmid = {32523039}, issn = {2045-2322}, mesh = {Animals ; Cell Adhesion/*genetics/physiology ; Cell Adhesion Molecules/*genetics/metabolism ; Cell Adhesion Molecules, Neuronal/genetics/metabolism ; Cell Line ; Computational Biology/methods ; Evolution, Molecular ; Humans ; Nectins/*genetics/metabolism ; }, abstract = {Nectin and nectin-like cell adhesion molecules (collectively referred as nectin family henceforth) are known to mediate cell-cell adhesion and related functions. While current literature suggests that nectins are prevalent in vertebrates, there are no in-depth analyses regarding the evolution of nectin family as a whole. In this work, we examine the evolutionary origin of the nectin family, using selected multicellular metazoans representing diverse clades whose whole genome sequencing data is available. Our results show that this family may have appeared earlier during metazoan evolution than previously believed. Systematic analyses indicate the order in which various members of nectin family seem to have evolved, with some nectin-like molecules appearing first, followed by the evolution of other members. Furthermore, we also found a few possible ancient homologues of nectins. While our study confirms the previous grouping of the nectin family into nectins and nectin-like molecules, it also shows poliovirus receptor (PVR/nectin-like-5) to possess characteristics that are intermediate between these two groups. Interestingly, except for PVR, the other nectins show surprising sequence conservations across species, suggesting evolutionary constraints due to critical roles played by these proteins.}, } @article {pmid32521019, year = {2020}, author = {Phansopa, C and Dunning, LT and Reid, JD and Christin, PA}, title = {Lateral Gene Transfer Acts As an Evolutionary Shortcut to Efficient C4 Biochemistry.}, journal = {Molecular biology and evolution}, volume = {37}, number = {11}, pages = {3094-3104}, pmid = {32521019}, issn = {1537-1719}, mesh = {Amino Acid Substitution ; *Biological Evolution ; *Gene Transfer, Horizontal ; Phosphoenolpyruvate Carboxylase/*genetics ; Photosynthesis/*genetics ; Poaceae/enzymology/*genetics ; }, abstract = {The adaptation of proteins for novel functions often requires changes in their kinetics via amino acid replacement. This process can require multiple mutations, and therefore extended periods of selection. The transfer of genes among distinct species might speed up the process, by providing proteins already adapted for the novel function. However, this hypothesis remains untested in multicellular eukaryotes. The grass Alloteropsis is an ideal system to test this hypothesis due to its diversity of genes encoding phosphoenolpyruvate carboxylase, an enzyme that catalyzes one of the key reactions in the C4 pathway. Different accessions of Alloteropsis either use native isoforms relatively recently co-opted from other functions or isoforms that were laterally acquired from distantly related species that evolved the C4 trait much earlier. By comparing the enzyme kinetics, we show that native isoforms with few amino acid replacements have substrate KM values similar to the non-C4 ancestral form, but exhibit marked increases in catalytic efficiency. The co-option of native isoforms was therefore followed by rapid catalytic improvements, which appear to rely on standing genetic variation observed within one species. Native C4 isoforms with more amino acid replacements exhibit additional changes in affinities, suggesting that the initial catalytic improvements are followed by gradual modifications. Finally, laterally acquired genes show both strong increases in catalytic efficiency and important changes in substrate handling. We conclude that the transfer of genes among distant species sharing the same physiological novelty creates an evolutionary shortcut toward more efficient enzymes, effectively accelerating evolution.}, } @article {pmid32517626, year = {2020}, author = {Laundon, D and Chrismas, N and Wheeler, G and Cunliffe, M}, title = {Chytrid rhizoid morphogenesis resembles hyphal development in multicellular fungi and is adaptive to resource availability.}, journal = {Proceedings. Biological sciences}, volume = {287}, number = {1928}, pages = {20200433}, pmid = {32517626}, issn = {1471-2954}, mesh = {Chytridiomycota/*physiology ; Fungi ; Hyphae/*growth & development ; Morphogenesis ; }, abstract = {Key to the ecological prominence of fungi is their distinctive cell biology, our understanding of which has been principally based on dikaryan hyphal and yeast forms. The early-diverging Chytridiomycota (chytrids) are ecologically important and a significant component of fungal diversity, yet their cell biology remains poorly understood. Unlike dikaryan hyphae, chytrids typically attach to substrates and feed osmotrophically via anucleate rhizoids. The evolution of fungal hyphae appears to have occurred from rhizoid-bearing lineages and it has been hypothesized that a rhizoid-like structure was the precursor to multicellular hyphae. Here, we show in a unicellular chytrid, Rhizoclosmatium globosum, that rhizoid development exhibits striking similarities with dikaryan hyphae and is adaptive to resource availability. Rhizoid morphogenesis exhibits analogous patterns to hyphal growth and is controlled by β-glucan-dependent cell wall synthesis and actin polymerization. Chytrid rhizoids growing from individual cells also demonstrate adaptive morphological plasticity in response to resource availability, developing a searching phenotype when carbon starved and spatial differentiation when interacting with particulate organic matter. We demonstrate that the adaptive cell biology and associated developmental plasticity considered characteristic of hyphal fungi are shared more widely across the Kingdom Fungi and therefore could be conserved from their most recent common ancestor.}, } @article {pmid32514997, year = {2020}, author = {Villagra, C and Frías-Lasserre, D}, title = {Epigenetic Molecular Mechanisms in Insects.}, journal = {Neotropical entomology}, volume = {49}, number = {5}, pages = {615-642}, doi = {10.1007/s13744-020-00777-8}, pmid = {32514997}, issn = {1678-8052}, mesh = {*Adaptation, Physiological ; Animals ; *Epigenesis, Genetic ; Insecta/*genetics ; Life Cycle Stages ; Phenotype ; Social Behavior ; }, abstract = {Insects are the largest animal group on Earth both in biomass and diversity. Their outstanding success has inspired genetics and developmental research, allowing the discovery of dynamic process explaining extreme phenotypic plasticity and canalization. Epigenetic molecular mechanisms (EMMs) are vital for several housekeeping functions in multicellular organisms, regulating developmental, ontogenetic trajectories and environmental adaptations. In Insecta, EMMs are involved in the development of extreme phenotypic divergences such as polyphenisms and eusocial castes. Here, we review the history of this research field and how the main EMMs found in insects help to understand their biological processes and diversity. EMMs in insects confer them rapid response capacity allowing insect either to change with plastic divergence or to keep constant when facing different stressors or stimuli. EMMs function both at intra as well as transgenerational scales, playing important roles in insect ecology and evolution. We discuss on how EMMs pervasive influences in Insecta require not only the control of gene expression but also the dynamic interplay of EMMs with further regulatory levels, including genetic, physiological, behavioral, and environmental among others, as was earlier proposed by the Probabilistic Epigenesis model and Developmental System Theory.}, } @article {pmid32510705, year = {2020}, author = {Palmer, MA and Nelson, CM}, title = {Fusion of airways during avian lung development constitutes a novel mechanism for the formation of continuous lumena in multicellular epithelia.}, journal = {Developmental dynamics : an official publication of the American Association of Anatomists}, volume = {249}, number = {11}, pages = {1318-1333}, doi = {10.1002/dvdy.215}, pmid = {32510705}, issn = {1097-0177}, support = {CA187692/CA/NCI NIH HHS/United States ; HL110335/HL/NHLBI NIH HHS/United States ; HL118532/HL/NHLBI NIH HHS/United States ; HL120142/HL/NHLBI NIH HHS/United States ; CMMI-1435853//National Science Foundation/International ; //Camille & Henry Dreyfus Foundation/International ; //David & Lucile Packard Foundation/International ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Basement Membrane/cytology/*embryology ; Chick Embryo ; *Chickens ; Lung/cytology/*embryology ; Respiratory Mucosa/cytology/*embryology ; }, abstract = {BACKGROUND: During development of the avian lung, the initially terminally branched epithelial tree later forms a continuous network of airways. This occurs via a large-scale epithelial fusion event, wherein airways that originate proximally collide with those that originate distally to form one continuous lumen.

RESULTS: Here, we found that prior to fusion, the epithelium of the embryonic chicken lung undergoes a shape change to permit the initiation and extension of new branches which contain the cells that initiate contact. These changes in epithelial shape coincide with the differentiation of smooth muscle cells that wrap the airways. From these nascent epithelial branches, individual cells form cytoskeletal protrusions that extend toward and form a bridge with their target airway. Additional cells then join the fusion site, forming a bilayered epithelium. During this process, the basement membrane around the prefusion epithelium degrades and then reforms after fusion. The epithelial bilayer then undergoes apoptosis, clearing the path between the two lumens.

CONCLUSIONS: The process of airway epithelial fusion in the developing chicken lung constitutes a novel mechanism for the generation of complex multicellular tubes and suggests a conserved role for smooth muscle in the shaping of airway epithelia.}, } @article {pmid32505051, year = {2020}, author = {Oates, AC}, title = {Waiting on the Fringe: cell autonomy and signaling delays in segmentation clocks.}, journal = {Current opinion in genetics & development}, volume = {63}, number = {}, pages = {61-70}, doi = {10.1016/j.gde.2020.04.008}, pmid = {32505051}, issn = {1879-0380}, mesh = {Animals ; *Body Patterning ; *Embryonic Development ; Membrane Proteins/*metabolism ; *Models, Biological ; Signal Transduction ; Vertebrates/*physiology ; }, abstract = {The rhythmic and sequential segmentation of the vertebrate body axis into somites during embryogenesis is governed by a multicellular, oscillatory patterning system called the segmentation clock. Despite many overt similarities between vertebrates, differences in genetic and dynamic regulation have been reported, raising intriguing questions about the evolution and conservation of this fundamental patterning process. Recent studies have brought insights into two important and related issues: (1) whether individual cells of segmentation clocks are autonomous oscillators or require cell-cell communication for their rhythm; and (2) the role of delays in the cell-cell communication that synchronizes the population of genetic oscillators. Although molecular details differ between species, conservation may exist at the level of the dynamics, hinting at rules for evolutionary trajectories in the system.}, } @article {pmid32499560, year = {2020}, author = {Tang, M and Xie, Q and Gimple, RC and Zhong, Z and Tam, T and Tian, J and Kidwell, RL and Wu, Q and Prager, BC and Qiu, Z and Yu, A and Zhu, Z and Mesci, P and Jing, H and Schimelman, J and Wang, P and Lee, D and Lorenzini, MH and Dixit, D and Zhao, L and Bhargava, S and Miller, TE and Wan, X and Tang, J and Sun, B and Cravatt, BF and Muotri, AR and Chen, S and Rich, JN}, title = {Three-dimensional bioprinted glioblastoma microenvironments model cellular dependencies and immune interactions.}, journal = {Cell research}, volume = {30}, number = {10}, pages = {833-853}, pmid = {32499560}, issn = {1748-7838}, support = {F30 CA217065/CA/NCI NIH HHS/United States ; R21 AR074763/AR/NIAMS NIH HHS/United States ; RC2 DK114785/DK/NIDDK NIH HHS/United States ; R01 CA238662/CA/NCI NIH HHS/United States ; F30 CA217066/CA/NCI NIH HHS/United States ; R01 CA169117/CA/NCI NIH HHS/United States ; P30 NS047101/NS/NINDS NIH HHS/United States ; R01 CA171652/CA/NCI NIH HHS/United States ; R01 NS089272/NS/NINDS NIH HHS/United States ; R01 NS087913/NS/NINDS NIH HHS/United States ; U19 MH107367/MH/NIMH NIH HHS/United States ; R01 NS103434/NS/NINDS NIH HHS/United States ; R24 DK099810/DK/NIDDK NIH HHS/United States ; F31 CA243296/CA/NCI NIH HHS/United States ; R35 CA197718/CA/NCI NIH HHS/United States ; R33 HD090662/HD/NICHD NIH HHS/United States ; R01 EB021857/EB/NIBIB NIH HHS/United States ; T32 GM007250/GM/NIGMS NIH HHS/United States ; R01 CA154130/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Bioprinting ; Cell Line, Tumor ; Cell Proliferation ; Glioblastoma/*immunology ; Humans ; Mice ; Neural Stem Cells ; Tissue Scaffolds ; Tumor Microenvironment/*immunology ; }, abstract = {Brain tumors are dynamic complex ecosystems with multiple cell types. To model the brain tumor microenvironment in a reproducible and scalable system, we developed a rapid three-dimensional (3D) bioprinting method to construct clinically relevant biomimetic tissue models. In recurrent glioblastoma, macrophages/microglia prominently contribute to the tumor mass. To parse the function of macrophages in 3D, we compared the growth of glioblastoma stem cells (GSCs) alone or with astrocytes and neural precursor cells in a hyaluronic acid-rich hydrogel, with or without macrophage. Bioprinted constructs integrating macrophage recapitulate patient-derived transcriptional profiles predictive of patient survival, maintenance of stemness, invasion, and drug resistance. Whole-genome CRISPR screening with bioprinted complex systems identified unique molecular dependencies in GSCs, relative to sphere culture. Multicellular bioprinted models serve as a scalable and physiologic platform to interrogate drug sensitivity, cellular crosstalk, invasion, context-specific functional dependencies, as well as immunologic interactions in a species-matched neural environment.}, } @article {pmid32496191, year = {2020}, author = {Booth, DS and King, N}, title = {Genome editing enables reverse genetics of multicellular development in the choanoflagellate Salpingoeca rosetta.}, journal = {eLife}, volume = {9}, number = {}, pages = {}, pmid = {32496191}, issn = {2050-084X}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {CRISPR-Cas Systems ; Choanoflagellata/*genetics/*growth & development ; Gene Editing ; Genome, Protozoan ; Lectins, C-Type/genetics ; Protozoan Proteins/genetics ; Reverse Genetics/*methods ; }, abstract = {In a previous study, we established a forward genetic screen to identify genes required for multicellular development in the choanoflagellate, Salpingoeca rosetta (Levin et al., 2014). Yet, the paucity of reverse genetic tools for choanoflagellates has hampered direct tests of gene function and impeded the establishment of choanoflagellates as a model for reconstructing the origin of their closest living relatives, the animals. Here we establish CRISPR/Cas9-mediated genome editing in S. rosetta by engineering a selectable marker to enrich for edited cells. We then use genome editing to disrupt the coding sequence of a S. rosetta C-type lectin gene, rosetteless, and thereby demonstrate its necessity for multicellular rosette development. This work advances S. rosetta as a model system in which to investigate how genes identified from genetic screens and genomic surveys function in choanoflagellates and evolved as critical regulators of animal biology.}, } @article {pmid32491889, year = {2020}, author = {Nguyen, M and Shiferaw, Y}, title = {Feedback control of calcium driven alternans in cardiac myocytes.}, journal = {Chaos (Woodbury, N.Y.)}, volume = {30}, number = {5}, pages = {053106}, pmid = {32491889}, issn = {1089-7682}, support = {R01 HL119095/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Calcium/*metabolism ; Calcium Signaling/*physiology ; Feedback ; Glucans/antagonists & inhibitors ; Myocytes, Cardiac/*physiology ; Ventricular Fibrillation ; }, abstract = {Cardiac alternans is a beat-to-beat alternation of the action potential duration (APD), which has been implicated as a possible cause of ventricular fibrillation. Previous studies have shown that alternans can originate via a period doubling bifurcation caused by the nonlinear dependence of the APD on the previous diastolic interval. In this case, it has been demonstrated that alternans can be eliminated by applying feedback control on the pacing cycle length. However, studies have shown that alternans can also originate due to unstable calcium (Ca) cycling in cardiac myocytes. In this study, we explore the effectiveness of APD feedback control to suppress alternans when the underlying instability is due to unstable Ca cycling. In particular, we explore the role of the bi-directional coupling between Ca and voltage and determine the effectiveness of feedback control under a wide range of conditions. We also analyze the applicability of feedback control on a coupled two cell system and show that APD control induces spatially out-of-phase alternans. We analyze the onset and the necessary conditions for the emergence of these out-of-phase patterns and assess the effectiveness of feedback control to suppress Ca driven alternans in a multi-cellular system.}, } @article {pmid32472019, year = {2020}, author = {Lawal, HM and Schilde, C and Kin, K and Brown, MW and James, J and Prescott, AR and Schaap, P}, title = {Cold climate adaptation is a plausible cause for evolution of multicellular sporulation in Dictyostelia.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {8797}, pmid = {32472019}, issn = {2045-2322}, support = {100293/Z/12/Z/WT_/Wellcome Trust/United Kingdom ; BB/K000799/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Acclimatization ; Biological Evolution ; Cold Climate ; Dictyostelium/*classification/*physiology ; Fossils/*parasitology ; Phylogeny ; Spores/physiology ; }, abstract = {Unicellular protozoa that encyst individually upon starvation evolved at least eight times into organisms that instead form multicellular fruiting bodies with spores. The Dictyostelia are the largest and most complex group of such organisms. They can be subdivided into 4 major groups, with many species in groups 1-3 having additionally retained encystment. To understand fitness differences between spores and cysts, we measured long-term survival of spores and cysts under climate-mimicking conditions, investigated spore and cyst ultrastructure, and related fitness characteristics to species ecology. We found that spores and cysts survived 22 °C equally well, but that spores survived wet and dry frost better than cysts, with group 4 spores being most resilient. Spore walls consist of three layers and those of cysts of maximally two, while spores were also more compacted than cysts, with group 4 spores being the most compacted. Group 4 species were frequently isolated from arctic and alpine zones, which was rarely the case for group 1-3 species. We inferred a fossil-calibrated phylogeny of Dictyostelia, which showed that its two major branches diverged 0.52 billion years ago, following several global glaciations. Our results suggest that Dictyostelium multicellular sporulation was a likely adaptation to a cold climate.}, } @article {pmid32471172, year = {2020}, author = {Demin, SI and Bogolyubov, DS and Granovitch, AI and Mikhailova, NA}, title = {New data on spermatogenic cyst formation and cellular composition of the testis in a marine gastropod, Littorina saxatilis.}, journal = {International journal of molecular sciences}, volume = {21}, number = {11}, pages = {}, pmid = {32471172}, issn = {1422-0067}, mesh = {Animals ; Gastropoda/*cytology ; Male ; Spermatogonia/ultrastructure ; Testis/*cytology ; }, abstract = {Knowledge of the testis structure is important for gastropod taxonomy and phylogeny, particularly for the comparative analysis of sympatric Littorina species. Observing fresh tissue and squashing fixed tissue with gradually increasing pressure, we have recently described a peculiar type of cystic spermatogenesis, rare in mollusks. It has not been documented in most mollusks until now. The testis of adult males consists of numerous lobules filled with multicellular cysts containing germline cells at different stages of differentiation. Each cyst is formed by one cyst cell of somatic origin. Here, we provide evidence for the existence of two ways of cyst formation in Littorina saxatilis. One of them begins with a goniablast cyst formation; it somewhat resembles cyst formation in Drosophila testes. The second way begins with capture of a free spermatogonium by the polyploid cyst cell which is capable to move along the gonad tissues. This way of cyst formation has not been described previously. Our data expand the understanding of the diversity of spermatogenesis types in invertebrates.}, } @article {pmid32471018, year = {2020}, author = {Kuroiwa, A}, title = {Enhancers, development, and evolution.}, journal = {Development, growth & differentiation}, volume = {62}, number = {5}, pages = {265-268}, doi = {10.1111/dgd.12683}, pmid = {32471018}, issn = {1440-169X}, mesh = {Animals ; *Biological Evolution ; Enhancer Elements, Genetic/*genetics ; Gene Expression Regulation, Developmental/*genetics ; Germ Layers ; }, abstract = {A single-celled fertilized egg develops into a complex, multicellular animal through a series of selection processes of developmental pathways. During these processes, regulatory genes exhibit spatiotemporally restricted expression under the control of the species-specific genetic program, and dictate developmental processes from germ layer formation to cellular differentiation. Elucidation of molecular mechanisms underlying developmental processes and also of mechanistic bases for morphological diversification during evolution is one of the central issues in contemporary developmental biology. Progress has been made due to recent technological innovations, such as high-throughput nucleotide sequencing, live-cell imaging, efficient genetic manipulation, and establishment of the organoid system, opening new avenues to the above issues.}, } @article {pmid32463355, year = {2020}, author = {Kuncha, SK and Venkadasamy, VL and Amudhan, G and Dahate, P and Kola, SR and Pottabathini, S and Kruparani, SP and Shekar, PC and Sankaranarayanan, R}, title = {Genomic innovation of ATD alleviates mistranslation associated with multicellularity in Animalia.}, journal = {eLife}, volume = {9}, number = {}, pages = {}, pmid = {32463355}, issn = {2050-084X}, support = {DST-INSPIRE//Department of Science and Technology, Ministry of Science and Technology/International ; J. C. Bose Fellowship//Science and Engineering Research Board/International ; Centre of Excellence//Department of Biotechnology , Ministry of Science and Technology/International ; Healthcare Theme project//Council of Scientific and Industrial Research/International ; Centre of Excellence//Department of Biotechnology, Ministry of Science and Technology/International ; }, mesh = {Amino Acyl-tRNA Synthetases/genetics/metabolism ; Animals ; Biological Evolution ; Cell Line ; Choanoflagellata/enzymology/genetics/metabolism ; Eukaryota/*enzymology/*genetics/metabolism ; Genome ; Genomics ; Humans ; Hydrolases/genetics/*metabolism ; Mice ; Oxidative Stress ; *Protein Biosynthesis ; RNA, Transfer/genetics/metabolism ; Threonine/metabolism ; }, abstract = {The emergence of multicellularity in Animalia is associated with increase in ROS and expansion of tRNA-isodecoders. tRNA expansion leads to misselection resulting in a critical error of L-Ala mischarged onto tRNA[Thr], which is proofread by Animalia-specific-tRNA Deacylase (ATD) in vitro. Here we show that in addition to ATD, threonyl-tRNA synthetase (ThrRS) can clear the error in cellular scenario. This two-tier functional redundancy for translation quality control breaks down during oxidative stress, wherein ThrRS is rendered inactive. Therefore, ATD knockout cells display pronounced sensitivity through increased mistranslation of threonine codons leading to cell death. Strikingly, we identify the emergence of ATD along with the error inducing tRNA species starting from Choanoflagellates thus uncovering an important genomic innovation required for multicellularity that occurred in unicellular ancestors of animals. The study further provides a plausible regulatory mechanism wherein the cellular fate of tRNAs can be switched from protein biosynthesis to non-canonical functions.}, } @article {pmid32462426, year = {2020}, author = {Casanova, JL and Abel, L}, title = {The human genetic determinism of life-threatening infectious diseases: genetic heterogeneity and physiological homogeneity?.}, journal = {Human genetics}, volume = {139}, number = {6-7}, pages = {681-694}, pmid = {32462426}, issn = {1432-1203}, support = {UL1 TR001866/TR/NCATS NIH HHS/United States ; R21 AI137371/AI/NIAID NIH HHS/United States ; R37 AI095983/AI/NIAID NIH HHS/United States ; R01 AI127564/AI/NIAID NIH HHS/United States ; R01 NS072381/NS/NINDS NIH HHS/United States ; U19 AI111143/AI/NIAID NIH HHS/United States ; R01 AI088364/AI/NIAID NIH HHS/United States ; P01 AI061093/AI/NIAID NIH HHS/United States ; }, mesh = {Communicable Diseases/*genetics/immunology/*pathology ; *Genetic Heterogeneity ; *Genetic Predisposition to Disease ; Humans ; Models, Genetic ; }, abstract = {Multicellular eukaryotes emerged late in evolution from an ocean of viruses, bacteria, archaea, and unicellular eukaryotes. These macroorganisms are exposed to and infected by a tremendous diversity of microorganisms. Those that are large enough can even be infected by multicellular fungi and parasites. Each interaction is unique, if only because it operates between two unique living organisms, in an infinite diversity of circumstances. This is neatly illustrated by the extraordinarily high level of interindividual clinical variability in human infections, even for a given pathogen, ranging from a total absence of clinical manifestations to death. We discuss here the idea that the determinism of human life-threatening infectious diseases can be governed by single-gene inborn errors of immunity, which are rarely Mendelian and frequently display incomplete penetrance. We briefly review the evidence in support of this notion obtained over the last two decades, referring to a number of focused and thorough reviews published by eminent colleagues in this issue of Human Genetics. It seems that almost any life-threatening infectious disease can be driven by at least one, and, perhaps, a great many diverse monogenic inborn errors, which may nonetheless be immunologically related. While the proportions of monogenic cases remain unknown, a picture in which genetic heterogeneity is combined with physiological homogeneity is emerging from these studies. A preliminary sketch of the human genetic architecture of severe infectious diseases is perhaps in sight.}, } @article {pmid32455487, year = {2020}, author = {Kumler, WE and Jorge, J and Kim, PM and Iftekhar, N and Koehl, MAR}, title = {Does Formation of Multicellular Colonies by Choanoflagellates Affect Their Susceptibility to Capture by Passive Protozoan Predators?.}, journal = {The Journal of eukaryotic microbiology}, volume = {67}, number = {5}, pages = {555-565}, doi = {10.1111/jeu.12808}, pmid = {32455487}, issn = {1550-7408}, mesh = {Choanoflagellata/*cytology ; *Food Chain ; Stramenopiles/*physiology ; }, abstract = {Microbial eukaryotes, critical links in aquatic food webs, are unicellular, but some, such as choanoflagellates, form multicellular colonies. Are there consequences to predator avoidance of being unicellular vs. forming larger colonies? Choanoflagellates share a common ancestor with animals and are used as model organisms to study the evolution of multicellularity. Escape in size from protozoan predators is suggested as a selective factor favoring evolution of multicellularity. Heterotrophic protozoans are categorized as suspension feeders, motile raptors, or passive predators that eat swimming prey which bump into them. We focused on passive predation and measured the mechanisms responsible for the susceptibility of unicellular vs. multicellular choanoflagellates, Salpingoeca helianthica, to capture by passive heliozoan predators, Actinosphaerium nucleofilum, which trap prey on axopodia radiating from the cell body. Microvideography showed that unicellular and colonial choanoflagellates entered the predator's capture zone at similar frequencies, but a greater proportion of colonies contacted axopodia. However, more colonies than single cells were lost during transport by axopodia to the cell body. Thus, feeding efficiency (proportion of prey entering the capture zone that were engulfed in phagosomes) was the same for unicellular and multicellular prey, suggesting that colony formation is not an effective defense against such passive predators.}, } @article {pmid32450967, year = {2020}, author = {McQueen, E and Rebeiz, M}, title = {On the specificity of gene regulatory networks: How does network co-option affect subsequent evolution?.}, journal = {Current topics in developmental biology}, volume = {139}, number = {}, pages = {375-405}, pmid = {32450967}, issn = {1557-8933}, support = {R01 GM112758/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Body Patterning/*genetics ; Evolution, Molecular ; *Gene Expression Regulation, Developmental ; *Gene Regulatory Networks ; Humans ; Models, Genetic ; Organ Specificity/*genetics ; Regulatory Elements, Transcriptional/*genetics ; Transcription Factors/*genetics/metabolism ; }, abstract = {The process of multicellular organismal development hinges upon the specificity of developmental programs: for different parts of the organism to form unique features, processes must exist to specify each part. This specificity is thought to be hardwired into gene regulatory networks, which activate cohorts of genes in particular tissues at particular times during development. However, the evolution of gene regulatory networks sometimes occurs by mechanisms that sacrifice specificity. One such mechanism is network co-option, in which existing gene networks are redeployed in new developmental contexts. While network co-option may offer an efficient mechanism for generating novel phenotypes, losses of tissue specificity at redeployed network genes could restrict the ability of the affected traits to evolve independently. At present, there has not been a detailed discussion regarding how tissue specificity of network genes might be altered due to gene network co-option at its initiation, as well as how trait independence can be retained or restored after network co-option. A lack of clarity about network co-option makes it more difficult to speculate on the long-term evolutionary implications of this mechanism. In this review, we will discuss the possible initial outcomes of network co-option, outline the mechanisms by which networks may retain or subsequently regain specificity after network co-option, and comment on some of the possible evolutionary consequences of network co-option. We place special emphasis on the need to consider selectively-neutral outcomes of network co-option to improve our understanding of the role of this mechanism in trait evolution.}, } @article {pmid32444651, year = {2020}, author = {Heaton, LLM and Jones, NS and Fricker, MD}, title = {A mechanistic explanation of the transition to simple multicellularity in fungi.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {2594}, pmid = {32444651}, issn = {2041-1723}, mesh = {Carbon/metabolism ; Cytoplasm/metabolism ; Fungi/*cytology/growth & development/*physiology ; Hyphae/cytology/growth & development ; *Models, Biological ; Nitrogen/metabolism ; Phosphorus/metabolism ; }, abstract = {Development of multicellularity was one of the major transitions in evolution and occurred independently multiple times in algae, plants, animals, and fungi. However recent comparative genome analyses suggest that fungi followed a different route to other eukaryotic lineages. To understand the driving forces behind the transition from unicellular fungi to hyphal forms of growth, we develop a comparative model of osmotrophic resource acquisition. This predicts that whenever the local resource is immobile, hard-to-digest, and nutrient poor, hyphal osmotrophs outcompete motile or autolytic unicellular osmotrophs. This hyphal advantage arises because transporting nutrients via a contiguous cytoplasm enables continued exploitation of remaining resources after local depletion of essential nutrients, and more efficient use of costly exoenzymes. The model provides a mechanistic explanation for the origins of multicellular hyphal organisms, and explains why fungi, rather than unicellular bacteria, evolved to dominate decay of recalcitrant, nutrient poor substrates such as leaf litter or wood.}, } @article {pmid32438974, year = {2020}, author = {Yang, S and Qu, G and Fu, B and Yang, F and Zeng, W and Cai, Y and Ye, T and Yang, Y and Deng, X and Xiang, W and Peng, D and Zhou, B}, title = {The function of KptA/Tpt1 gene - a minor review.}, journal = {Functional plant biology : FPB}, volume = {47}, number = {7}, pages = {577-591}, doi = {10.1071/FP19159}, pmid = {32438974}, issn = {1445-4416}, mesh = {NAD ; Phosphotransferases (Alcohol Group Acceptor) ; RNA, Transfer ; Saccharomyces cerevisiae/genetics ; *Saccharomyces cerevisiae Proteins ; }, abstract = {Rapid response of uni- and multicellular organisms to environmental changes and their own growth is achieved through a series of molecular mechanisms, often involving modification of macromolecules, including nucleic acids, proteins and lipids. The ADP-ribosylation process has ability to modify these different macromolecules in cells, and is closely related to the biological processes, such as DNA replication, transcription, signal transduction, cell division, stress, microbial aging and pathogenesis. In addition, tRNA plays an essential role in the regulation of gene expression, as effector molecules, no-load tRNA affects the overall gene expression level of cells under some nutritional stress. KptA/Tpt1 is an essential phosphotransferase in the process of pre-tRNA splicing, releasing mature tRNA and participating in ADP-ribose. The objective of this review is concluding the gene structure, the evolution history and the function of KptA/Tpt1 from prokaryote to eukaryote organisms. At the same time, the results of promoter elements analysis were also shown in the present study. Moreover, the problems in the function of KptA/Tpt1 that have not been clarified at the present time are summarised, and some suggestions to solve those problems are given. This review presents no only a summary of clear function of KptA/Tpt1 in the process of tRNA splicing and ADP-ribosylation of organisms, but also gives some proposals to clarify unclear problems of it in the future.}, } @article {pmid32428501, year = {2020}, author = {Arendt, D}, title = {The Evolutionary Assembly of Neuronal Machinery.}, journal = {Current biology : CB}, volume = {30}, number = {10}, pages = {R603-R616}, doi = {10.1016/j.cub.2020.04.008}, pmid = {32428501}, issn = {1879-0445}, mesh = {Animals ; *Biological Evolution ; Neurons/*physiology ; Synapses/physiology ; Synaptic Transmission/*physiology ; }, abstract = {Neurons are highly specialized cells equipped with a sophisticated molecular machinery for the reception, integration, conduction and distribution of information. The evolutionary origin of neurons remains unsolved. How did novel and pre-existing proteins assemble into the complex machinery of the synapse and of the apparatus conducting current along the neuron? In this review, the step-wise assembly of functional modules in neuron evolution serves as a paradigm for the emergence and modification of molecular machinery in the evolution of cell types in multicellular organisms. The pre-synaptic machinery emerged through modification of calcium-regulated large vesicle release, while the postsynaptic machinery has different origins: the glutamatergic postsynapse originated through the fusion of a sensory signaling module and a module for filopodial outgrowth, while the GABAergic postsynapse incorporated an ancient actin regulatory module. The synaptic junction, in turn, is built around two adhesion modules controlled by phosphorylation, which resemble septate and adherens junctions. Finally, neuronal action potentials emerged via a series of duplications and modifications of voltage-gated ion channels. Based on these origins, key molecular innovations are identified that led to the birth of the first neuron in animal evolution.}, } @article {pmid32421773, year = {2020}, author = {Tollis, M and Schneider-Utaka, AK and Maley, CC}, title = {The Evolution of Human Cancer Gene Duplications across Mammals.}, journal = {Molecular biology and evolution}, volume = {37}, number = {10}, pages = {2875-2886}, pmid = {32421773}, issn = {1537-1719}, support = {U54 CA217376/CA/NCI NIH HHS/United States ; R01 CA185138/CA/NCI NIH HHS/United States ; U2C CA233254/CA/NCI NIH HHS/United States ; R01 CA170595/CA/NCI NIH HHS/United States ; R01 CA140657/CA/NCI NIH HHS/United States ; P01 CA091955/CA/NCI NIH HHS/United States ; R01 CA149566/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Evolution, Molecular ; Gene Dosage ; *Gene Duplication ; *Genes, Neoplasm ; Humans ; *Life History Traits ; Longevity ; Mammals/*genetics ; Mole Rats/genetics ; }, abstract = {Cancer is caused by genetic alterations that affect cellular fitness, and multicellular organisms have evolved mechanisms to suppress cancer such as cell cycle checkpoints and apoptosis. These pathways may be enhanced by the addition of tumor suppressor gene paralogs or deletion of oncogenes. To provide insights to the evolution of cancer suppression across the mammalian radiation, we estimated copy numbers for 548 human tumor suppressor gene and oncogene homologs in 63 mammalian genome assemblies. The naked mole rat contained the most cancer gene copies, consistent with the extremely low rates of cancer found in this species. We found a positive correlation between a species' cancer gene copy number and its longevity, but not body size, contrary to predictions from Peto's Paradox. Extremely long-lived mammals also contained more copies of caretaker genes in their genomes, suggesting that the maintenance of genome integrity is an essential form of cancer prevention in long-lived species. We found the strongest association between longevity and copy numbers of genes that are both germline and somatic tumor suppressor genes, suggesting that selection has acted to suppress both hereditary and sporadic cancers. We also found a strong relationship between the number of tumor suppressor genes and the number of oncogenes in mammalian genomes, suggesting that complex regulatory networks mediate the balance between cell proliferation and checks on tumor progression. This study is the first to investigate cancer gene expansions across the mammalian radiation and provides a springboard for potential human therapies based on evolutionary medicine.}, } @article {pmid32415185, year = {2020}, author = {Hörandl, E and Hadacek, F}, title = {Oxygen, life forms, and the evolution of sexes in multicellular eukaryotes.}, journal = {Heredity}, volume = {125}, number = {1-2}, pages = {1-14}, pmid = {32415185}, issn = {1365-2540}, mesh = {Animals ; *Biological Evolution ; *Eukaryota ; Female ; Fungi/genetics ; Male ; Oxidative Stress ; *Oxygen ; Reproduction ; Sex Chromosomes ; Sexual Behavior, Animal ; }, abstract = {The evolutionary advantage of different sexual systems in multicellular eukaryotes is still not well understood, because the differentiation into male and female individuals halves offspring production compared with asexuality. Here we propose that various physiological adaptations to oxidative stress could have forged sessility versus motility, and consequently the evolution of sexual systems in multicellular animals, plants, and fungi. Photosynthesis causes substantial amounts of oxidative stress in photoautotrophic plants and, likewise, oxidative chemistry of polymer breakdown, cellulose and lignin, for saprotrophic fungi. In both cases, its extent precludes motility, an additional source of oxidative stress. Sessile life form and the lack of neuronal systems, however, limit options for mate recognition and adult sexual selection, resulting in inefficient mate-searching systems. Hence, sessility requires that all individuals can produce offspring, which is achieved by hermaphroditism in plants and/or by multiple mating types in fungi. In animals, motility requires neuronal systems, and muscle activity, both of which are highly sensitive to oxidative damage. As a consequence, motility has evolved in animals as heterotrophic organisms that (1) are not photosynthetically active, and (2) are not primary decomposers. Adaptations to motility provide prerequisites for an active mating behavior and efficient mate-searching systems. These benefits compensate for the "cost of males", and may explain the early evolution of sex chromosomes in metazoans. We conclude that different sexual systems evolved under the indirect physiological constraints of lifestyles.}, } @article {pmid32399193, year = {2020}, author = {Zardoya, R}, title = {Recent advances in understanding mitochondrial genome diversity.}, journal = {F1000Research}, volume = {9}, number = {}, pages = {}, pmid = {32399193}, issn = {2046-1402}, mesh = {Animals ; *Evolution, Molecular ; Fungi/genetics ; *Genome, Mitochondrial ; Introns ; Mitochondria ; Plants/genetics ; RNA Editing ; }, abstract = {Ever since its discovery, the double-stranded DNA contained in the mitochondria of eukaryotes has fascinated researchers because of its bacterial endosymbiotic origin, crucial role in encoding subunits of the respiratory complexes, compact nature, and specific inheritance mechanisms. In the last few years, high-throughput sequencing techniques have accelerated the sequencing of mitochondrial genomes (mitogenomes) and uncovered the great diversity of organizations, gene contents, and modes of replication and transcription found in living eukaryotes. Some early divergent lineages of unicellular eukaryotes retain certain synteny and gene content resembling those observed in the genomes of alphaproteobacteria (the inferred closest living group of mitochondria), whereas others adapted to anaerobic environments have drastically reduced or even lost the mitogenome. In the three main multicellular lineages of eukaryotes, mitogenomes have pursued diverse evolutionary trajectories in which different types of molecules (circular versus linear and single versus multipartite), gene structures (with or without self-splicing introns), gene contents, gene orders, genetic codes, and transfer RNA editing mechanisms have been selected. Whereas animals have evolved a rather compact mitochondrial genome between 11 and 50 Kb in length with a highly conserved gene content in bilaterians, plants exhibit large mitochondrial genomes of 66 Kb to 11.3 Mb with large intergenic repetitions prone to recombination, and fungal mitogenomes have intermediate sizes of 12 to 236 Kb.}, } @article {pmid32355003, year = {2020}, author = {Lazzaro, BP and Zasloff, M and Rolff, J}, title = {Antimicrobial peptides: Application informed by evolution.}, journal = {Science (New York, N.Y.)}, volume = {368}, number = {6490}, pages = {}, pmid = {32355003}, issn = {1095-9203}, support = {R01 AI141385/AI/NIAID NIH HHS/United States ; /ERC_/European Research Council/International ; }, mesh = {Animals ; Anti-Bacterial Agents/*pharmacology ; Antimicrobial Cationic Peptides/chemistry/*genetics/*pharmacology ; Drosophila Proteins/genetics/pharmacology ; *Drug Resistance, Bacterial ; Drug Synergism ; *Evolution, Molecular ; Humans ; Polymorphism, Genetic ; Translational Research, Biomedical ; }, abstract = {Antimicrobial peptides (AMPs) are essential components of immune defenses of multicellular organisms and are currently in development as anti-infective drugs. AMPs have been classically assumed to have broad-spectrum activity and simple kinetics, but recent evidence suggests an unexpected degree of specificity and a high capacity for synergies. Deeper evaluation of the molecular evolution and population genetics of AMP genes reveals more evidence for adaptive maintenance of polymorphism in AMP genes than has previously been appreciated, as well as adaptive loss of AMP activity. AMPs exhibit pharmacodynamic properties that reduce the evolution of resistance in target microbes, and AMPs may synergize with one another and with conventional antibiotics. Both of these properties make AMPs attractive for translational applications. However, if AMPs are to be used clinically, it is crucial to understand their natural biology in order to lessen the risk of collateral harm and avoid the crisis of resistance now facing conventional antibiotics.}, } @article {pmid32353148, year = {2020}, author = {Hoffman, SK and Seitz, KW and Havird, JC and Weese, DA and Santos, SR}, title = {Phenotypic Comparability from Genotypic Variability among Physically Structured Microbial Consortia.}, journal = {Integrative and comparative biology}, volume = {60}, number = {2}, pages = {288-303}, doi = {10.1093/icb/icaa022}, pmid = {32353148}, issn = {1557-7023}, mesh = {Bacteria/*genetics ; Cyanobacteria/genetics ; *Genotype ; Hawaii ; Microbial Consortia/*genetics ; *Phenotype ; }, abstract = {Microbiomes represent the collective bacteria, archaea, protist, fungi, and virus communities living in or on individual organisms that are typically multicellular eukaryotes. Such consortia have become recognized as having significant impacts on the development, health, and disease status of their hosts. Since understanding the mechanistic connections between an individual's genetic makeup and their complete set of traits (i.e., genome to phenome) requires consideration at different levels of biological organization, this should include interactions with, and the organization of, microbial consortia. To understand microbial consortia organization, we elucidated the genetic constituents among phenotypically similar (and hypothesized functionally-analogous) layers (i.e., top orange, second orange, pink, and green layers) in the unique laminated orange cyanobacterial-bacterial crusts endemic to Hawaii's anchialine ecosystem. High-throughput amplicon sequencing of ribosomal RNA hypervariable regions (i.e., Bacteria-specific V6 and Eukarya-biased V9) revealed microbial richness increasing by crust layer depth, with samples of a given layer more similar to different layers from the same geographic site than to their phenotypically-analogous layer from different sites. Furthermore, samples from sites on the same island were more similar to each other, regardless of which layer they originated from, than to analogous layers from another island. However, cyanobacterial and algal taxa were abundant in all surface and bottom layers, with anaerobic and chemoautotrophic taxa concentrated in the middle two layers, suggesting crust oxygenation from both above and below. Thus, the arrangement of oxygenated vs. anoxygenated niches in these orange crusts is functionally distinct relative to other laminated cyanobacterial-bacterial communities examined to date, with convergent evolution due to similar environmental conditions a likely driver for these phenotypically comparable but genetically distinct microbial consortia.}, } @article {pmid32330159, year = {2020}, author = {Safdari, H and Kalirad, A and Picioreanu, C and Tusserkani, R and Goliaei, B and Sadeghi, M}, title = {Noise-driven cell differentiation and the emergence of spatiotemporal patterns.}, journal = {PloS one}, volume = {15}, number = {4}, pages = {e0232060}, pmid = {32330159}, issn = {1932-6203}, mesh = {Adaptation, Biological/*physiology ; Animals ; Artifacts ; *Biodiversity ; *Biological Evolution ; Cell Differentiation/physiology ; Cell Lineage/physiology ; Humans ; Models, Biological ; Models, Theoretical ; Phenotype ; Spatio-Temporal Analysis ; }, abstract = {The emergence of phenotypic diversity in a population of cells and their arrangement in space and time is one of the most fascinating features of living systems. In fact, understanding multicellularity is unthinkable without explaining the proximate and the ultimate causes of cell differentiation in time and space. Simpler forms of cell differentiation can be found in unicellular organisms, such as bacterial biofilm, where reversible cell differentiation results in phenotypically diverse populations. In this manuscript, we attempt to start with the simple case of reversible nongenetic phenotypic to construct a model of differentiation and pattern formation. Our model, which we refer to as noise-driven differentiation (NDD) model, is an attempt to consider the prevalence of noise in biological systems, alongside what is known about genetic switches and signaling, to create a simple model which generates spatiotemporal patterns from bottom-up. Our simulations indicate that the presence of noise in cells can lead to reversible differentiation and the addition of signaling can create spatiotemporal pattern.}, } @article {pmid32315081, year = {2020}, author = {Rainey, L and Deevi, RK and McClements, J and Khawaja, H and Watson, CJ and Roudier, M and Van Schaeybroeck, S and Campbell, FC}, title = {Fundamental control of grade-specific colorectal cancer morphology by Src regulation of ezrin-centrosome engagement.}, journal = {The Journal of pathology}, volume = {251}, number = {3}, pages = {310-322}, doi = {10.1002/path.5452}, pmid = {32315081}, issn = {1096-9896}, support = {MR/L015110/1/MRC_/Medical Research Council/United Kingdom ; L015110/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Caco-2 Cells ; Centrosome/*enzymology/pathology ; Colorectal Neoplasms/*enzymology/genetics/pathology ; Cytoskeletal Proteins/genetics/*metabolism ; Focal Adhesion Kinase 1/genetics/metabolism ; HCT116 Cells ; Humans ; *Mitosis ; Neoplasm Grading ; PTEN Phosphohydrolase/genetics/metabolism ; Signal Transduction ; src-Family Kinases/genetics/*metabolism ; }, abstract = {The phenotypic spectrum of colorectal cancer (CRC) is remarkably diverse, with seemingly endless variations in cell shape, mitotic figures and multicellular configurations. Despite this morphological complexity, histological grading of collective phenotype patterns provides robust prognostic stratification in CRC. Although mechanistic understanding is incomplete, previous studies have shown that the cortical protein ezrin controls diversification of cell shape, mitotic figure geometry and multicellular architecture, in 3D organotypic CRC cultures. Because ezrin is a substrate of Src tyrosine kinase that is frequently overexpressed in CRC, we investigated Src regulation of ezrin and morphogenic growth in 3D CRC cultures. Here we show that Src perturbations disrupt CRC epithelial spatial organisation. Aberrant Src activity suppresses formation of the cortical ezrin cap that anchors interphase centrosomes. In CRC cells with a normal centrosome number, these events lead to mitotic spindle misorientation, perturbation of cell cleavage, abnormal epithelial stratification, apical membrane misalignment, multilumen formation and evolution of cribriform multicellular morphology, a feature of low-grade cancer. In isogenic CRC cells with centrosome amplification, aberrant Src signalling promotes multipolar mitotic spindle formation, pleomorphism and morphological features of high-grade cancer. Translational studies in archival human CRC revealed associations between Src intensity, multipolar mitotic spindle frequency and high-grade cancer morphology. Collectively, our study reveals Src regulation of CRC morphogenic growth via ezrin-centrosome engagement and uncovers combined perturbations underlying transition to high-grade CRC morphology. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.}, } @article {pmid32305342, year = {2020}, author = {Friedman, DA and Johnson, BR and Linksvayer, TA}, title = {Distributed physiology and the molecular basis of social life in eusocial insects.}, journal = {Hormones and behavior}, volume = {122}, number = {}, pages = {104757}, doi = {10.1016/j.yhbeh.2020.104757}, pmid = {32305342}, issn = {1095-6867}, mesh = {Animals ; Ants/genetics/physiology ; Bees/genetics/physiology ; Behavior, Animal/*physiology ; Biological Evolution ; Cooperative Behavior ; Genome, Insect/*physiology ; Insecta/*genetics/*physiology ; Isoptera/genetics/physiology ; Nesting Behavior/physiology ; Phenotype ; *Social Behavior ; }, abstract = {The traditional focus of physiological and functional genomic research is on molecular processes that play out within a single multicellular organism. In the colonial (eusocial) insects such as ants, bees, and termites, molecular and behavioral responses of interacting nestmates are tightly linked, and key physiological processes are regulated at the scale of the colony. Such colony-level physiological processes regulate nestmate physiology in a distributed fashion, through various social communication mechanisms. As a result of physiological decentralization over evolutionary time, organismal mechanisms, for example related to pheromone detection, hormone signaling, and neural signaling pathways, are deployed in novel contexts to influence nestmate and colony traits. Here we explore how functional genomic, physiological, and behavioral studies can benefit from considering the traits of eusocial insects in this light. We highlight functional genomic work exploring how nestmate-level and colony-level traits arise and are influenced by interactions among physiologically-specialized nestmates of various developmental stages. We also consider similarities and differences between nestmate-level (organismal) and colony-level (superorganismal) physiological processes, and make specific hypotheses regarding the physiology of eusocial taxa. Integrating theoretical models of distributed systems with empirical functional genomics approaches will be useful in addressing fundamental questions related to the evolution of eusociality and collective behavior in natural systems.}, } @article {pmid32301582, year = {2020}, author = {Naranjo-Ortiz, MA and Gabaldón, T}, title = {Fungal evolution: cellular, genomic and metabolic complexity.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {95}, number = {5}, pages = {1198-1232}, pmid = {32301582}, issn = {1469-185X}, support = {PT17/0009/0023 - ISCIII-SGEFI/ERDF//INB Grant/International ; H2020-MSCA-IF-2017-793699//Marie Sklodowska-Curie/International ; ERC-2016-724173//European Union's Horizon 2020/International ; SGR423//Catalan Research Agency (AGAUR)/International ; //CERCA Programme/Generalitat de Catalunya/International ; //European Regional Development Fund/International ; //Spanish Ministry of Science and Innovation/International ; }, mesh = {Adaptation, Physiological ; Animals ; *Fungi/genetics ; *Genome, Fungal ; Genomics ; Plants/genetics ; }, abstract = {The question of how phenotypic and genomic complexity are inter-related and how they are shaped through evolution is a central question in biology that historically has been approached from the perspective of animals and plants. In recent years, however, fungi have emerged as a promising alternative system to address such questions. Key to their ecological success, fungi present a broad and diverse range of phenotypic traits. Fungal cells can adopt many different shapes, often within a single species, providing them with great adaptive potential. Fungal cellular organizations span from unicellular forms to complex, macroscopic multicellularity, with multiple transitions to higher or lower levels of cellular complexity occurring throughout the evolutionary history of fungi. Similarly, fungal genomes are very diverse in their architecture. Deep changes in genome organization can occur very quickly, and these phenomena are known to mediate rapid adaptations to environmental changes. Finally, the biochemical complexity of fungi is huge, particularly with regard to their secondary metabolites, chemical products that mediate many aspects of fungal biology, including ecological interactions. Herein, we explore how the interplay of these cellular, genomic and metabolic traits mediates the emergence of complex phenotypes, and how this complexity is shaped throughout the evolutionary history of Fungi.}, } @article {pmid32290841, year = {2020}, author = {Gao, F and Cai, Y and Kapranov, P and Xu, D}, title = {Reverse-genetics studies of lncRNAs-what we have learnt and paths forward.}, journal = {Genome biology}, volume = {21}, number = {1}, pages = {93}, pmid = {32290841}, issn = {1474-760X}, mesh = {Animals ; Evolution, Molecular ; Phenotype ; RNA, Long Noncoding/*physiology ; Reverse Genetics ; Vertebrates/genetics ; }, abstract = {Long non-coding RNAs (lncRNAs) represent a major fraction of the transcriptome in multicellular organisms. Although a handful of well-studied lncRNAs are broadly recognized as biologically meaningful, the fraction of such transcripts out of the entire collection of lncRNAs remains a subject of vigorous debate. Here we review the evidence for and against biological functionalities of lncRNAs and attempt to arrive at potential modes of lncRNA functionality that would reconcile the contradictory conclusions. Finally, we discuss different strategies of phenotypic analyses that could be used to investigate such modes of lncRNA functionality.}, } @article {pmid32285363, year = {2020}, author = {Low, LA and Sutherland, M and Lumelsky, N and Selimovic, S and Lundberg, MS and Tagle, DA}, title = {Organs-on-a-Chip.}, journal = {Advances in experimental medicine and biology}, volume = {1230}, number = {}, pages = {27-42}, doi = {10.1007/978-3-030-36588-2_3}, pmid = {32285363}, issn = {0065-2598}, mesh = {Animals ; Drug Development ; Drug Discovery ; Humans ; *Lab-On-A-Chip Devices ; *Tissue Array Analysis ; }, abstract = {Organs-on-chips, also known as "tissue chips" or microphysiological systems (MPS), are bioengineered microsystems capable of recreating aspects of human organ physiology and function and are in vitro tools with multiple applications in drug discovery and development. The ability to recapitulate human and animal tissues in physiologically relevant three-dimensional, multi-cellular environments allows applications in the drug development field, including; (1) use in assessing the safety and toxicity testing of potential therapeutics during early-stage preclinical drug development; (2) confirmation of drug/therapeutic efficacy in vitro; and (3) disease modeling of human tissues to recapitulate pathophysiology within specific subpopulations and even individuals, thereby advancing precision medicine efforts. This chapter will discuss the development and evolution of three-dimensional organ models over the past decade, and some of the opportunities offered by MPS technology that are not available through current standard two-dimensional cell cultures, or three-dimensional organoid systems. This chapter will outline future avenues of research in the MPS field, how cutting-edge biotechnology advances are expanding the applications for these systems, and discuss the current and future potential and challenges remaining for the field to address.}, } @article {pmid32284424, year = {2020}, author = {Fouchard, J and Wyatt, TPJ and Proag, A and Lisica, A and Khalilgharibi, N and Recho, P and Suzanne, M and Kabla, A and Charras, G}, title = {Curling of epithelial monolayers reveals coupling between active bending and tissue tension.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {117}, number = {17}, pages = {9377-9383}, pmid = {32284424}, issn = {1091-6490}, support = {BB/M003280/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/M002578/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Biomechanical Phenomena ; Cell Adhesion ; Cell Line ; Dogs ; Elasticity ; Epithelium/*physiology ; Stress, Mechanical ; }, abstract = {Epithelial monolayers are two-dimensional cell sheets which compartmentalize the body and organs of multicellular organisms. Their morphogenesis during development or pathology results from patterned endogenous and exogenous forces and their interplay with tissue mechanical properties. In particular, bending of epithelia is thought to result from active torques generated by the polarization of myosin motors along their apicobasal axis. However, the contribution of these out-of-plane forces to morphogenesis remains challenging to evaluate because of the lack of direct mechanical measurement. Here we use epithelial curling to characterize the out-of-plane mechanics of epithelial monolayers. We find that curls of high curvature form spontaneously at the free edge of epithelial monolayers devoid of substrate in vivo and in vitro. Curling originates from an enrichment of myosin in the basal domain that generates an active spontaneous curvature. By measuring the force necessary to flatten curls, we can then estimate the active torques and the bending modulus of the tissue. Finally, we show that the extent of curling is controlled by the interplay between in-plane and out-of-plane stresses in the monolayer. Such mechanical coupling emphasizes a possible role for in-plane stresses in shaping epithelia during morphogenesis.}, } @article {pmid32283732, year = {2020}, author = {Annenkova, NV and Giner, CR and Logares, R}, title = {Tracing the Origin of Planktonic Protists in an Ancient Lake.}, journal = {Microorganisms}, volume = {8}, number = {4}, pages = {}, pmid = {32283732}, issn = {2076-2607}, abstract = {Ancient lakes are among the most interesting models for evolution studies because their biodiversity is the result of a complex combination of migration and speciation. Here, we investigate the origin of single celled planktonic eukaryotes from the oldest lake in the world-Lake Baikal (Russia). By using 18S rDNA metabarcoding, we recovered 1414 Operational Taxonomic Units (OTUs) belonging to protists populating surface waters (1-50 m) and representing pico/nano-sized cells. The recovered communities resembled other lacustrine freshwater assemblages found elsewhere, especially the taxonomically unclassified protists. However, our results suggest that a fraction of Baikal protists could belong to glacial relicts and have close relationships with marine/brackish species. Moreover, our results suggest that rapid radiation may have occurred among some protist taxa, partially mirroring what was already shown for multicellular organisms in Lake Baikal. We found 16% of the OTUs belonging to potential species flocks in Stramenopiles, Alveolata, Opisthokonta, Archaeplastida, Rhizaria, and Hacrobia. Putative flocks predominated in Chrysophytes, which are highly diverse in Lake Baikal. Also, the 18S rDNA of a number of species (7% of the total) differed >10% from other known sequences. These taxa as well as those belonging to the flocks may be endemic to Lake Baikal. Overall, our study points to novel diversity of planktonic protists in Lake Baikal, some of which may have emerged in situ after evolutionary diversification.}, } @article {pmid32282832, year = {2020}, author = {Brun-Usan, M and Thies, C and Watson, RA}, title = {How to fit in: The learning principles of cell differentiation.}, journal = {PLoS computational biology}, volume = {16}, number = {4}, pages = {e1006811}, pmid = {32282832}, issn = {1553-7358}, mesh = {Adaptation, Physiological/*genetics ; Animals ; Biological Evolution ; *Cell Differentiation ; Computer Simulation ; Developmental Biology/*methods ; Environment ; Gene Regulatory Networks ; Genetic Variation ; Learning ; Models, Biological ; Phenotype ; Selection, Genetic ; }, abstract = {Cell differentiation in multicellular organisms requires cells to respond to complex combinations of extracellular cues, such as morphogen concentrations. Some models of phenotypic plasticity conceptualise the response as a relatively simple function of a single environmental cues (e.g. a linear function of one cue), which facilitates rigorous analysis. Conversely, more mechanistic models such those implementing GRNs allows for a more general class of response functions but makes analysis more difficult. Therefore, a general theory describing how cells integrate multi-dimensional signals is lacking. In this work, we propose a theoretical framework for understanding the relationships between environmental cues (inputs) and phenotypic responses (outputs) underlying cell plasticity. We describe the relationship between environment and cell phenotype using logical functions, making the evolution of cell plasticity equivalent to a simple categorisation learning task. This abstraction allows us to apply principles derived from learning theory to understand the evolution of multi-dimensional plasticity. Our results show that natural selection is capable of discovering adaptive forms of cell plasticity associated with complex logical functions. However, developmental dynamics cause simpler functions to evolve more readily than complex ones. By using conceptual tools derived from learning theory we show that this developmental bias can be interpreted as a learning bias in the acquisition of plasticity functions. Because of that bias, the evolution of plasticity enables cells, under some circumstances, to display appropriate plastic responses to environmental conditions that they have not experienced in their evolutionary past. This is possible when the selective environment mirrors the bias of the developmental dynamics favouring the acquisition of simple plasticity functions-an example of the necessary conditions for generalisation in learning systems. These results illustrate the functional parallelisms between learning in neural networks and the action of natural selection on environmentally sensitive gene regulatory networks. This offers a theoretical framework for the evolution of plastic responses that integrate information from multiple cues, a phenomenon that underpins the evolution of multicellularity and developmental robustness.}, } @article {pmid32278076, year = {2020}, author = {Hehenberger, E and Eitel, M and Fortunato, SAV and Miller, DJ and Keeling, PJ and Cahill, MA}, title = {Early eukaryotic origins and metazoan elaboration of MAPR family proteins.}, journal = {Molecular phylogenetics and evolution}, volume = {148}, number = {}, pages = {106814}, doi = {10.1016/j.ympev.2020.106814}, pmid = {32278076}, issn = {1095-9513}, mesh = {Amino Acid Sequence ; Animals ; Eukaryota/*metabolism ; Evolution, Molecular ; Membrane Proteins/chemistry/*metabolism ; Phylogeny ; Protein Binding ; Protein Domains ; Receptors, Progesterone/chemistry/genetics/*metabolism ; }, abstract = {The membrane-associated progesterone receptor (MAPR) family consists of heme-binding proteins containing a cytochrome b5 (cytb5) domain characterized by the presence of a MAPR-specific interhelical insert region (MIHIR) between helices 3 and 4 of the canonical cytb5-domain fold. Animals possess three MAPR genes (PGRMC-like, Neuferricin and Neudesin). Here we show that all three animal MAPR genes were already present in the common ancestor of the opisthokonts (comprising animals and fungi as well as related single-celled taxa). All three MAPR genes acquired extensions C-terminal to the cytb5 domain, either before or with the evolution of animals. The archetypical MAPR protein, progesterone receptor membrane component 1 (PGRMC1), contains phosphorylated tyrosines Y139 and Y180. The combination of Y139/Y180 appeared in the common ancestor of cnidarians and bilaterians, along with an early embryological organizer and synapsed neurons, and is strongly conserved in all bilaterian animals. A predicted protein interaction motif in the PGRMC1 MIHIR is potentially regulated by Y139 phosphorylation. A multilayered model of animal MAPR function acquisition includes some pre-metazoan functions (e.g., heme binding and cytochrome P450 interactions) and some acquired animal-specific functions that involve regulation of strongly conserved protein interaction motifs acquired by animals (Metazoa). This study provides a conceptual framework for future studies, against which especially PGRMC1's multiple functions can perhaps be stratified and functionally dissected.}, } @article {pmid32272915, year = {2020}, author = {Tikhonenkov, DV and Hehenberger, E and Esaulov, AS and Belyakova, OI and Mazei, YA and Mylnikov, AP and Keeling, PJ}, title = {Insights into the origin of metazoan multicellularity from predatory unicellular relatives of animals.}, journal = {BMC biology}, volume = {18}, number = {1}, pages = {39}, pmid = {32272915}, issn = {1741-7007}, support = {18-14-00239//Russian Science Foundation/International ; 227301//Natural Sciences and Engineering Research Council of Canada (CA)/International ; }, mesh = {Animals ; *Biological Evolution ; Eukaryota/*physiology ; Evolution, Molecular ; Invertebrates/*physiology ; Phylogeny ; Predatory Behavior ; }, abstract = {BACKGROUND: The origin of animals from their unicellular ancestor was one of the most important events in evolutionary history, but the nature and the order of events leading up to the emergence of multicellular animals are still highly uncertain. The diversity and biology of unicellular relatives of animals have strongly informed our understanding of the transition from single-celled organisms to the multicellular Metazoa. Here, we analyze the cellular structures and complex life cycles of the novel unicellular holozoans Pigoraptor and Syssomonas (Opisthokonta), and their implications for the origin of animals.

RESULTS: Syssomonas and Pigoraptor are characterized by complex life cycles with a variety of cell types including flagellates, amoeboflagellates, amoeboid non-flagellar cells, and spherical cysts. The life cycles also include the formation of multicellular aggregations and syncytium-like structures, and an unusual diet for single-celled opisthokonts (partial cell fusion and joint sucking of a large eukaryotic prey), all of which provide new insights into the origin of multicellularity in Metazoa. Several existing models explaining the origin of multicellular animals have been put forward, but these data are interestingly consistent with one, the "synzoospore hypothesis."

CONCLUSIONS: The feeding modes of the ancestral metazoan may have been more complex than previously thought, including not only bacterial prey, but also larger eukaryotic cells and organic structures. The ability to feed on large eukaryotic prey could have been a powerful trigger in the formation and development of both aggregative (e.g., joint feeding, which also implies signaling) and clonal (e.g., hypertrophic growth followed by palintomy) multicellular stages that played important roles in the emergence of multicellular animals.}, } @article {pmid32260425, year = {2020}, author = {Simeone, P and Bologna, G and Lanuti, P and Pierdomenico, L and Guagnano, MT and Pieragostino, D and Del Boccio, P and Vergara, D and Marchisio, M and Miscia, S and Mariani-Costantini, R}, title = {Extracellular Vesicles as Signaling Mediators and Disease Biomarkers across Biological Barriers.}, journal = {International journal of molecular sciences}, volume = {21}, number = {7}, pages = {}, pmid = {32260425}, issn = {1422-0067}, mesh = {Biomarkers/*metabolism ; Cell Communication ; Disease/*genetics ; Extracellular Vesicles/genetics/*metabolism ; Genetic Predisposition to Disease ; Humans ; Immunity ; Signal Transduction ; }, abstract = {Extracellular vesicles act as shuttle vectors or signal transducers that can deliver specific biological information and have progressively emerged as key regulators of organized communities of cells within multicellular organisms in health and disease. Here, we survey the evolutionary origin, general characteristics, and biological significance of extracellular vesicles as mediators of intercellular signaling, discuss the various subtypes of extracellular vesicles thus far described and the principal methodological approaches to their study, and review the role of extracellular vesicles in tumorigenesis, immunity, non-synaptic neural communication, vascular-neural communication through the blood-brain barrier, renal pathophysiology, and embryo-fetal/maternal communication through the placenta.}, } @article {pmid32253306, year = {2020}, author = {Shao, S and Koh, M and Schultz, PG}, title = {Expanding the genetic code of the human hematopoietic system.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {117}, number = {16}, pages = {8845-8849}, pmid = {32253306}, issn = {1091-6490}, support = {R01 GM132071/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acids/*genetics ; Animals ; Cell Differentiation/*genetics ; Fetal Blood/cytology ; Gene Transfer Techniques ; Genetic Code ; Genetic Vectors/*genetics ; HEK293 Cells ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells/*physiology ; Herpesvirus 4, Human/genetics ; Humans ; Mice ; Mice, Inbred NOD ; Plasmids/genetics ; Primary Cell Culture/methods ; Protein Engineering/*methods ; Transfection/methods ; Transplantation Chimera ; Transplantation, Heterologous/methods ; }, abstract = {The genetic incorporation of noncanonical amino acids (ncAAs) into proteins has been realized in bacteria, yeast, and mammalian cells, and recently, in multicellular organisms including plants and animals. However, the addition of new building blocks to the genetic code of tissues from human origin has not yet been achieved. To this end, we report a self-replicating Epstein-Barr virus-based episomal vector for the long-term encoding of ncAAs in human hematopoietic stem cells and reconstitution of this genetically engineered hematopoietic system in mice.}, } @article {pmid32251406, year = {2020}, author = {Kazer, SW and Aicher, TP and Muema, DM and Carroll, SL and Ordovas-Montanes, J and Miao, VN and Tu, AA and Ziegler, CGK and Nyquist, SK and Wong, EB and Ismail, N and Dong, M and Moodley, A and Berger, B and Love, JC and Dong, KL and Leslie, A and Ndhlovu, ZM and Ndung'u, T and Walker, BD and Shalek, AK}, title = {Integrated single-cell analysis of multicellular immune dynamics during hyperacute HIV-1 infection.}, journal = {Nature medicine}, volume = {26}, number = {4}, pages = {511-518}, pmid = {32251406}, issn = {1546-170X}, support = {UM1 AI100663/AI/NIAID NIH HHS/United States ; 107752/Z/15/Z/WT_/Wellcome Trust/United Kingdom ; R01 AI138546/AI/NIAID NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; T32 GM007753/GM/NIGMS NIH HHS/United States ; T32 GM087237/GM/NIGMS NIH HHS/United States ; P01 AI039671/AI/NIAID NIH HHS/United States ; R01 AI145305/AI/NIAID NIH HHS/United States ; T32 GM008313/GM/NIGMS NIH HHS/United States ; U19 AI089992/AI/NIAID NIH HHS/United States ; P30 AI060354/AI/NIAID NIH HHS/United States ; RM1 HG006193/HG/NHGRI NIH HHS/United States ; R01 HL095791/HL/NHLBI NIH HHS/United States ; 210662/Z/18/Z/WT_/Wellcome Trust/United Kingdom ; UM1 AI144462/AI/NIAID NIH HHS/United States ; R01 AI118544/AI/NIAID NIH HHS/United States ; R01 HL134539/HL/NHLBI NIH HHS/United States ; K08 AI118538/AI/NIAID NIH HHS/United States ; R37 AI067073/AI/NIAID NIH HHS/United States ; U24 AI118672/AI/NIAID NIH HHS/United States ; /WT_/Wellcome Trust/United Kingdom ; U54 CA217377/CA/NCI NIH HHS/United States ; R01 DA046277/DA/NIDA NIH HHS/United States ; }, mesh = {Acute Disease ; Acute-Phase Reaction/genetics/immunology/pathology ; Adolescent ; Adult ; *Cell Communication/genetics/immunology ; Female ; Gene Expression Profiling ; Gene Regulatory Networks/immunology ; HIV Infections/*genetics/*immunology/pathology ; HIV-1/genetics/pathogenicity ; Humans ; Immunity, Cellular/*physiology ; Killer Cells, Natural/immunology/metabolism ; Leukocytes, Mononuclear/metabolism/pathology ; Longitudinal Studies ; Sequence Analysis, RNA/methods ; Single-Cell Analysis/*methods ; Systems Integration ; T-Lymphocytes, Cytotoxic/immunology/metabolism ; Viral Load/genetics/immunology ; Young Adult ; }, abstract = {Cellular immunity is critical for controlling intracellular pathogens, but individual cellular dynamics and cell-cell cooperativity in evolving human immune responses remain poorly understood. Single-cell RNA-sequencing (scRNA-seq) represents a powerful tool for dissecting complex multicellular behaviors in health and disease[1,2] and nominating testable therapeutic targets[3]. Its application to longitudinal samples could afford an opportunity to uncover cellular factors associated with the evolution of disease progression without potentially confounding inter-individual variability[4]. Here, we present an experimental and computational methodology that uses scRNA-seq to characterize dynamic cellular programs and their molecular drivers, and apply it to HIV infection. By performing scRNA-seq on peripheral blood mononuclear cells from four untreated individuals before and longitudinally during acute infection[5], we were powered within each to discover gene response modules that vary by time and cell subset. Beyond previously unappreciated individual- and cell-type-specific interferon-stimulated gene upregulation, we describe temporally aligned gene expression responses obscured in bulk analyses, including those involved in proinflammatory T cell differentiation, prolonged monocyte major histocompatibility complex II upregulation and persistent natural killer (NK) cell cytolytic killing. We further identify response features arising in the first weeks of infection, for example proliferating natural killer cells, which potentially may associate with future viral control. Overall, our approach provides a unified framework for characterizing multiple dynamic cellular responses and their coordination.}, } @article {pmid32234827, year = {2020}, author = {Pienta, KJ and Hammarlund, EU and Axelrod, R and Amend, SR and Brown, JS}, title = {Convergent Evolution, Evolving Evolvability, and the Origins of Lethal Cancer.}, journal = {Molecular cancer research : MCR}, volume = {18}, number = {6}, pages = {801-810}, pmid = {32234827}, issn = {1557-3125}, support = {U01 CA196390/CA/NCI NIH HHS/United States ; U54 CA143803/CA/NCI NIH HHS/United States ; R01 CA170595/CA/NCI NIH HHS/United States ; U54 CA143970/CA/NCI NIH HHS/United States ; U54 CA163124/CA/NCI NIH HHS/United States ; P01 CA093900/CA/NCI NIH HHS/United States ; U01 CA143055/CA/NCI NIH HHS/United States ; U54 CA210173/CA/NCI NIH HHS/United States ; }, mesh = {*Evolution, Molecular ; *Genetic Variation ; Humans ; *Mutation ; Neoplasms/*genetics/*pathology ; *Selection, Genetic ; }, abstract = {Advances in curative treatment to remove the primary tumor have increased survival of localized cancers for most solid tumor types, yet cancers that have spread are typically incurable and account for >90% of cancer-related deaths. Metastatic disease remains incurable because, somehow, tumors evolve resistance to all known compounds, including therapies. In all of these incurable patients, de novo lethal cancer evolves capacities for both metastasis and resistance. Therefore, cancers in different patients appear to follow the same eco-evolutionary path that independently manifests in affected patients. This convergent outcome, that always includes the ability to metastasize and exhibit resistance, demands an explanation beyond the slow and steady accrual of stochastic mutations. The common denominator may be that cancer starts as a speciation event when a unicellular protist breaks away from its multicellular host and initiates a cancer clade within the patient. As the cancer cells speciate and diversify further, some evolve the capacity to evolve: evolvability. Evolvability becomes a heritable trait that influences the available variation of other phenotypes that can then be acted upon by natural selection. Evolving evolvability may be an adaptation for cancer cells. By generating and maintaining considerable heritable variation, the cancer clade can, with high certainty, serendipitously produce cells resistant to therapy and cells capable of metastasizing. Understanding that cancer cells can swiftly evolve responses to novel and varied stressors create opportunities for adaptive therapy, double-bind therapies, and extinction therapies; all involving strategic decision making that steers and anticipates the convergent coevolutionary responses of the cancers.}, } @article {pmid32234519, year = {2020}, author = {Nelson, WJ}, title = {The Glue that Binds Us: The Hunt for the Molecular Basis for Multicellularity.}, journal = {Cell}, volume = {181}, number = {3}, pages = {495-497}, doi = {10.1016/j.cell.2020.03.017}, pmid = {32234519}, issn = {1097-4172}, mesh = {Animals ; Awards and Prizes ; Biophysical Phenomena ; Cadherins/*metabolism/*physiology ; Canada ; Cell Adhesion/physiology ; Cell Communication/*physiology ; History, 20th Century ; History, 21st Century ; Homeostasis/physiology ; Humans ; Male ; }, abstract = {This year's Canada Gairdner International Prize is shared by Rolf Kemler and Masatoshi Takeichi for the discovery of the cadherin family of Ca[2+]-dependent cell-cell adhesion proteins, which play essential roles in animal evolution, tissue development, and homeostasis, and are disrupted in human cancers.}, } @article {pmid32224105, year = {2020}, author = {Mikhailovsky, G and Gordon, R}, title = {Shuffling type of biological evolution based on horizontal gene transfer and the biosphere gene pool hypothesis.}, journal = {Bio Systems}, volume = {193-194}, number = {}, pages = {104131}, doi = {10.1016/j.biosystems.2020.104131}, pmid = {32224105}, issn = {1872-8324}, mesh = {*Biological Evolution ; DNA Shuffling/*methods ; Eukaryota/genetics ; *Evolution, Molecular ; *Gene Pool ; Gene Transfer, Horizontal/*genetics ; Prokaryotic Cells/physiology ; }, abstract = {Widespread horizontal gene transfer (HGT) may appear a significant factor that accelerates biological evolution. Here we look at HGT primarily from the point of view of prokaryote clones, which we take as the descendants of a single cell, all of whom have exactly the same nucleotide sequence. Any novelty that emerges as a random mutation, creating a new clone, could either disappear before its first HGT, or survive for a period and be transferred to another clone. Due to the chain character of HGT, each gene with an adaptive mutation is thus spread among numerous existing clones, creating further new clones in the process. This makes propagation far faster than elimination, and such genes become practically immortal and form a kind of "biosphere gene pool" (BGP). Not all of these genes exist in every clone, and moreover not all of them are expressed. A significant fraction of the BGP includes of genes repressed by regulatory genes. However, these genes express often enough to be subject to natural selection. In a changing environment, both repressed and expressed genes, after transferring to another clone, may prove useful in an alternative environment, and this will give rise to new clones. This mechanism for testing repressed genes for adaptability can be thought as a "shuffle of a deck of genes" by analogy with shuffling a deck of cards. In the Archean and Proterozoic eons, both BGP and the operational part of each genome were rather poor, and the probability of incorporation of randomly expressed genes into the operational part of each genome was very small. Accordingly, biological evolution during these eons was slow due to rare adaptive mutations. This explains why the realm of prokaryotes as the sole organisms on Earth lasted so long. However, over about 3.5 billion years before the Phanerozoic eon, the BGP gradually accumulated a huge number of genes. Each of them was useful in a certain environment of past eras. We suggest that multicellular eukaryotes that appeared at the end of the Proterozoic eon could shuffle these genes accumulated in BGP via HGT from prokaryotes that live in these multicellular organisms. Perhaps this was the cause of the "Cambrian explosion" and the high (and increasing) rate of evolution in the Phanerozoic eon compared with the Archean and Proterozoic.}, } @article {pmid32220299, year = {2020}, author = {Aich, M and Chakraborty, D}, title = {Role of lncRNAs in stem cell maintenance and differentiation.}, journal = {Current topics in developmental biology}, volume = {138}, number = {}, pages = {73-112}, doi = {10.1016/bs.ctdb.2019.11.003}, pmid = {32220299}, issn = {1557-8933}, mesh = {Animals ; Cell Differentiation ; Cell Proliferation ; Embryonic Stem Cells/cytology/*physiology ; *Gene Expression Regulation, Developmental ; Humans ; Pluripotent Stem Cells/cytology/*physiology ; Promoter Regions, Genetic ; RNA, Long Noncoding/genetics/*metabolism ; Regulatory Sequences, Nucleic Acid ; }, abstract = {Embryonic Stem cells are widely studied to elucidate the disease and developmental processes because of their capability to differentiate into cells of any lineage, Pervasive transcription is a distinct feature of all multicellular organisms and genomic elements such as enhancers and bidirectional or unidirectional promoters regulate these processes. Thousands of loci in each species produce a class of transcripts called noncoding RNAs (ncRNAs), that are well known for their influential regulatory roles in multiple biological processes including stem cell pluripotency and differentiation. The number of lncRNA species increases in more complex organisms highlighting the importance of RNA-based control in the evolution of multicellular organisms. Over the past decade, numerous studies have shed light on lncRNA biogenesis and functional significance in the cell and the organism. In this review, we focus primarily on lncRNAs affecting the stem cell state and developmental pathways.}, } @article {pmid32198827, year = {2021}, author = {Koehl, MAR}, title = {Selective factors in the evolution of multicellularity in choanoflagellates.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {336}, number = {3}, pages = {315-326}, doi = {10.1002/jez.b.22941}, pmid = {32198827}, issn = {1552-5015}, mesh = {Animals ; Bacteria ; Behavior, Animal ; *Biological Evolution ; Choanoflagellata/*growth & development/*physiology ; Predatory Behavior ; }, abstract = {Choanoflagellates, unicellular eukaryotes that can form multicellular colonies by cell division and that share a common ancestor with animals, are used as a model system to study functional consequences of being unicellular versus colonial. This review examines performance differences between unicellular and multicellular choanoflagellates in swimming, feeding, and avoiding predation, to provide insights about possible selective advantages of being multicellular for the protozoan ancestors of animals. Each choanoflagellate cell propels water by beating a single flagellum and captures bacterial prey on a collar of microvilli around the flagellum. Formation of multicellular colonies does not improve the swimming performance, but the flux of prey-bearing water to the collars of some of the cells in colonies of certain configurations can be greater than for single cells. Colony geometry appears to affect whether cells in colonies catch more prey per cell per time than do unicellular choanoflagellates. Although multicellular choanoflagellates show chemokinetic behavior in response to oxygen, only the unicellular dispersal stage (fast swimmers without collars) use pH signals to aggregate in locations where bacterial prey might be abundant. Colonies produce larger hydrodynamic signals than do single cells, and raptorial protozoan predators capture colonies while ignoring single cells. In contrast, ciliate predators entrain both single cells and colonies in their feeding currents, but reject larger colonies, whereas passive heliozoan predators show no preference. Thus, the ability of choanoflagellate cells to differentiate into different morphotypes, including multicellular forms, in response to variable aquatic environments might have provided a selective advantage to the ancestors of animals.}, } @article {pmid32191693, year = {2020}, author = {Rossine, FW and Martinez-Garcia, R and Sgro, AE and Gregor, T and Tarnita, CE}, title = {Eco-evolutionary significance of "loners".}, journal = {PLoS biology}, volume = {18}, number = {3}, pages = {e3000642}, pmid = {32191693}, issn = {1545-7885}, support = {F32 GM103062/GM/NIGMS NIH HHS/United States ; K25 GM098875/GM/NIGMS NIH HHS/United States ; P50 GM071508/GM/NIGMS NIH HHS/United States ; R01 GM098407/GM/NIGMS NIH HHS/United States ; }, mesh = {Biological Evolution ; Dictyostelium/growth & development/*physiology ; Models, Biological ; Quorum Sensing ; Spatio-Temporal Analysis ; Stochastic Processes ; }, abstract = {Loners-individuals out of sync with a coordinated majority-occur frequently in nature. Are loners incidental byproducts of large-scale coordination attempts, or are they part of a mosaic of life-history strategies? Here, we provide empirical evidence of naturally occurring heritable variation in loner behavior in the model social amoeba Dictyostelium discoideum. We propose that Dictyostelium loners-cells that do not join the multicellular life stage-arise from a dynamic population-partitioning process, the result of each cell making a stochastic, signal-based decision. We find evidence that this imperfectly synchronized multicellular development is affected by both abiotic (environmental porosity) and biotic (signaling) factors. Finally, we predict theoretically that when a pair of strains differing in their partitioning behavior coaggregate, cross-signaling impacts slime-mold diversity across spatiotemporal scales. Our findings suggest that loners could be critical to understanding collective and social behaviors, multicellular development, and ecological dynamics in D. discoideum. More broadly, across taxa, imperfect coordination of collective behaviors might be adaptive by enabling diversification of life-history strategies.}, } @article {pmid32191325, year = {2020}, author = {Merényi, Z and Prasanna, AN and Wang, Z and Kovács, K and Hegedüs, B and Bálint, B and Papp, B and Townsend, JP and Nagy, LG}, title = {Unmatched Level of Molecular Convergence among Deeply Divergent Complex Multicellular Fungi.}, journal = {Molecular biology and evolution}, volume = {37}, number = {8}, pages = {2228-2240}, pmid = {32191325}, issn = {1537-1719}, support = {758161/ERC_/European Research Council/International ; }, mesh = {Ascomycota/*genetics ; Basidiomycota/*genetics ; *Biological Evolution ; Fruiting Bodies, Fungal/*genetics ; Gene Expression Regulation, Developmental ; Multigene Family ; }, abstract = {Convergent evolution is pervasive in nature, but it is poorly understood how various constraints and natural selection limit the diversity of evolvable phenotypes. Here, we analyze the transcriptome across fruiting body development to understand the independent evolution of complex multicellularity in the two largest clades of fungi-the Agarico- and Pezizomycotina. Despite >650 My of divergence between these clades, we find that very similar sets of genes have convergently been co-opted for complex multicellularity, followed by expansions of their gene families by duplications. Over 82% of shared multicellularity-related gene families were expanding in both clades, indicating a high prevalence of convergence also at the gene family level. This convergence is coupled with a rich inferred repertoire of multicellularity-related genes in the most recent common ancestor of the Agarico- and Pezizomycotina, consistent with the hypothesis that the coding capacity of ancestral fungal genomes might have promoted the repeated evolution of complex multicellularity. We interpret this repertoire as an indication of evolutionary predisposition of fungal ancestors for evolving complex multicellular fruiting bodies. Our work suggests that evolutionary convergence may happen not only when organisms are closely related or are under similar selection pressures, but also when ancestral genomic repertoires render certain evolutionary trajectories more likely than others, even across large phylogenetic distances.}, } @article {pmid32188079, year = {2020}, author = {Gura, C and Rogers, SO}, title = {Metatranscriptomic and Metagenomic Analysis of Biological Diversity in Subglacial Lake Vostok (Antarctica).}, journal = {Biology}, volume = {9}, number = {3}, pages = {}, pmid = {32188079}, issn = {2079-7737}, abstract = {A combined metatranscriptomic and metagenomic study of Vostok (Antarctica) ice core sections from glacial, basal, and lake water accretion ice yielded sequences that indicated a wide variety of species and possible conditions at the base of the glacier and in subglacial Lake Vostok. Few organisms were in common among the basal ice and accretion ice samples, suggesting little transmission of viable organisms from the basal ice meltwater into the lake water. Additionally, samples of accretion ice, each of which originated from water in several locations of the shallow embayment, exhibit only small amounts of mixing of species. The western-most portion of the embayment had very low numbers of organisms, likely due to biologically challenging conditions. Increasing numbers of organisms were found progressing from west to east, up to approximately 7 km into the embayment. At that point, the numbers of unique sequences and sequence reads from thermophilic, thermotolerant, psychrophilic, and psychrotolerant organisms increased dramatically, as did sequences from alkaliphilic, alkalitolerant, acidophilic, and acidotolerant sequences. The number of unique and total sequences were positively associated with increases in concentrations of Na[+], Ca[2+], Mg[2+], SO4[2-], Cl[-], total amino acids, and non-purgeable organic carbon. The numbers of unique sequences from organisms reported from soil, sediment, ice, aquatic, marine, animal, and plant (probably pollen) sources also peaked in this region, suggesting that this was the most biologically active region. The confluence of the high numbers of organisms, physiologies, and metabolic capabilities suggests the presence of energy and nutrient sources in the eastern half of the embayment. Data from the main basin suggested a cold oligotrophic environment containing fewer organisms. In addition to bacteria, both the basal ice and accretion ice contained sequences from a diverse assemblage of eukaryotes, as well as from bacteria that are known to be associated with multicellular eukaryotes.}, } @article {pmid32168362, year = {2020}, author = {Morgan, MD and Patin, E and Jagla, B and Hasan, M and Quintana-Murci, L and Marioni, JC}, title = {Quantitative genetic analysis deciphers the impact of cis and trans regulation on cell-to-cell variability in protein expression levels.}, journal = {PLoS genetics}, volume = {16}, number = {3}, pages = {e1008686}, pmid = {32168362}, issn = {1553-7404}, support = {MR/M008975/1/MRC_/Medical Research Council/United Kingdom ; 105045/Z/14/Z/WT_/Wellcome Trust/United Kingdom ; 17197/CRUK_/Cancer Research UK/United Kingdom ; /DH_/Department of Health/United Kingdom ; }, mesh = {Alleles ; Databases, Genetic ; Female ; Gene Expression/*genetics ; Gene Expression Profiling/methods ; Gene Expression Regulation/*genetics ; Genetic Testing/methods ; Genome-Wide Association Study/methods ; Humans ; Immune System/metabolism ; Immunity/genetics ; Male ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci/genetics ; Selection, Genetic/genetics ; }, abstract = {Identifying the factors that shape protein expression variability in complex multi-cellular organisms has primarily focused on promoter architecture and regulation of single-cell expression in cis. However, this targeted approach has to date been unable to identify major regulators of cell-to-cell gene expression variability in humans. To address this, we have combined single-cell protein expression measurements in the human immune system using flow cytometry with a quantitative genetics analysis. For the majority of proteins whose variability in expression has a heritable component, we find that genetic variants act in trans, with notably fewer variants acting in cis. Furthermore, we highlight using Mendelian Randomization that these variability-Quantitative Trait Loci might be driven by the cis regulation of upstream genes. This indicates that natural selection may balance the impact of gene regulation in cis with downstream impacts on expression variability in trans.}, } @article {pmid32163611, year = {2020}, author = {Nedelcu, AM and Michod, RE}, title = {Stress Responses Co-Opted for Specialized Cell Types During the Early Evolution of Multicellularity: The Role of Stress in the Evolution of Cell Types Can Be Traced Back to the Early Evolution of Multicellularity.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {42}, number = {5}, pages = {e2000029}, doi = {10.1002/bies.202000029}, pmid = {32163611}, issn = {1521-1878}, support = {//Natural Sciences and Engineering Research Council (NSERC) of Canada and Harrison McCain Foundation/International ; NNX13AH41G/NASA/NASA/United States ; MCB-1412395//National Science Foundation/International ; //Natural Sciences and Engineering Research Council of Canada/International ; NNX13AH41G/NASA/NASA/United States ; }, mesh = {*Biological Evolution ; Humans ; Phylogeny ; }, } @article {pmid32146616, year = {2020}, author = {Fuchs, M and Lohmann, JU}, title = {Aiming for the top: non-cell autonomous control of shoot stem cells in Arabidopsis.}, journal = {Journal of plant research}, volume = {133}, number = {3}, pages = {297-309}, pmid = {32146616}, issn = {1618-0860}, mesh = {Arabidopsis/*growth & development ; Arabidopsis Proteins ; Gene Expression Regulation, Plant ; Homeodomain Proteins ; Meristem/*cytology ; Plant Shoots/*cytology ; Stem Cells/*cytology ; }, abstract = {In multicellular organisms, not all cells are created equal. Instead, organismal complexity is achieved by specialisation and division of labour between distinct cell types. Therefore, the organism depends on the presence, correct proportion and function of all cell types. It follows that early development is geared towards setting up the basic body plan and to specify cell lineages. Since plants employ a post-embryonic mode of development, the continuous growth and addition of new organs require a source of new cells, as well as a strict regulation of cellular composition throughout the entire life-cycle. To meet these demands, evolution has brought about complex regulatory systems to maintain and control continuously active stem cell systems. Here, we review recent work on the mechanisms of non cell-autonomous control of shoot stem cells in the model plant Arabidopsis thaliana with a strong focus on the cell-to-cell mobility and function of the WUSCHEL homeodomain transcription factor.}, } @article {pmid32143753, year = {2020}, author = {Klesen, S and Hill, K and Timmermans, MCP}, title = {Small RNAs as plant morphogens.}, journal = {Current topics in developmental biology}, volume = {137}, number = {}, pages = {455-480}, doi = {10.1016/bs.ctdb.2019.11.001}, pmid = {32143753}, issn = {1557-8933}, mesh = {Cell Communication ; *Gene Expression Regulation, Developmental ; MicroRNAs/genetics ; *Plant Development ; *Plant Physiological Phenomena ; Plant Proteins/genetics/*metabolism ; Plants/*genetics ; RNA/*genetics ; RNA, Small Interfering/genetics ; Signal Transduction ; }, abstract = {The coordination of cell fate decisions within complex multicellular structures rests on intercellular communication. To generate ordered patterns, cells need to know their relative positions within the growing structure. This is commonly achieved via the production and perception of mobile signaling molecules. In animal systems, such positional signals often act as morphogens and subdivide a field of cells into domains of discrete cell identities using a threshold-based readout of their mobility gradient. Reflecting the independent origin of multicellularity, plants evolved distinct signaling mechanisms to drive cell fate decisions. Many of the basic principles underlying developmental patterning are, however, shared between animals and plants, including the use of signaling gradients to provide positional information. In plant development, small RNAs can act as mobile instructive signals, and similar to classical morphogens in animals, employ a threshold-based readout of their mobility gradient to generate precisely defined cell fate boundaries. Given the distinctive nature of peptide morphogens and small RNAs, how might mechanisms underlying the function of traditionally morphogens be adapted to create morphogen-like behavior using small RNAs? In this review, we highlight the contributions of mobile small RNAs to pattern formation in plants and summarize recent studies that have advanced our understanding regarding the formation, stability, and interpretation of small RNA gradients.}, } @article {pmid32139673, year = {2020}, author = {Han, H and Yan, A and Li, L and Zhu, Y and Feng, B and Liu, X and Zhou, Y}, title = {A signal cascade originated from epidermis defines apical-basal patterning of Arabidopsis shoot apical meristems.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {1214}, pmid = {32139673}, issn = {2041-1723}, mesh = {Arabidopsis/*embryology/genetics/*metabolism ; Arabidopsis Proteins/metabolism ; Base Sequence ; *Body Patterning ; Gene Expression Regulation, Plant ; Green Fluorescent Proteins/metabolism ; Homeodomain Proteins/metabolism ; Meristem/*embryology/*metabolism ; MicroRNAs/genetics/metabolism ; Plant Epidermis/*metabolism ; Promoter Regions, Genetic/genetics ; Protein Binding ; *Signal Transduction ; Stem Cell Niche ; Up-Regulation/genetics ; }, abstract = {In multicellular organisms, a long-standing question is how spatial patterns of distinct cell types are initiated and maintained during continuous cell division and proliferation. Along the vertical axis of plant shoot apical meristems (SAMs), stem cells are located at the top while cells specifying the stem cells are located more basally, forming a robust apical-basal pattern. We previously found that in Arabidopsis SAMs, the HAIRY MERISTEM (HAM) family transcription factors form a concentration gradient from the epidermis to the interior cell layers, and this gradient is essential for the stem cell specification and the apical-basal patterning of the SAMs. Here, we uncover that epidermis specific transcription factors, ARABIDOPSIS THALIANA MERISTEM LAYER 1 (ATML1) and its close homolog, define the concentration gradient of HAM in the SAM through activating a group of microRNAs. This study provides a molecular framework linking the epidermis-derived signal to the stem cell homeostasis in plants.}, } @article {pmid32133683, year = {2020}, author = {Horton, MB and Hawkins, ED and Heinzel, S and Hodgkin, PD}, title = {Speculations on the evolution of humoral adaptive immunity.}, journal = {Immunology and cell biology}, volume = {98}, number = {6}, pages = {439-448}, pmid = {32133683}, issn = {1440-1711}, mesh = {*Adaptive Immunity ; *Biological Evolution ; Cell Differentiation ; Humans ; *Immunity, Humoral ; }, abstract = {The protection of a multicellular organism from infection, at both cell and humoral levels, has been a tremendous driver of gene selection and cellular response strategies. Here we focus on a critical event in the development of humoral immunity: The transition from principally innate responses to a system of adaptive cell selection, with all the attendant mechanical problems that must be solved in order for it to work effectively. Here we review recent advances, but our major goal is to highlight that the development of adaptive immunity resulted from the adoption, reuse and repurposing of an ancient, autonomous cellular program that combines and exploits three titratable cellular fate timers. We illustrate how this common cell machinery recurs and appears throughout biology, and has been essential for the evolution of complex organisms, at many levels of scale.}, } @article {pmid32130880, year = {2020}, author = {González, A and Hall, MN and Lin, SC and Hardie, DG}, title = {AMPK and TOR: The Yin and Yang of Cellular Nutrient Sensing and Growth Control.}, journal = {Cell metabolism}, volume = {31}, number = {3}, pages = {472-492}, doi = {10.1016/j.cmet.2020.01.015}, pmid = {32130880}, issn = {1932-7420}, support = {204766/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; 204766/WT_/Wellcome Trust/United Kingdom ; }, mesh = {AMP-Activated Protein Kinases/chemistry/genetics/*metabolism ; Animals ; Cell Proliferation ; Cells/*metabolism ; DNA Damage ; Humans ; Nutrients/*metabolism ; TOR Serine-Threonine Kinases/*metabolism ; }, abstract = {The AMPK (AMP-activated protein kinase) and TOR (target-of-rapamycin) pathways are interlinked, opposing signaling pathways involved in sensing availability of nutrients and energy and regulation of cell growth. AMPK (Yin, or the "dark side") is switched on by lack of energy or nutrients and inhibits cell growth, while TOR (Yang, or the "bright side") is switched on by nutrient availability and promotes cell growth. Genes encoding the AMPK and TOR complexes are found in almost all eukaryotes, suggesting that these pathways arose very early during eukaryotic evolution. During the development of multicellularity, an additional tier of cell-extrinsic growth control arose that is mediated by growth factors, but these often act by modulating nutrient uptake so that AMPK and TOR remain the underlying regulators of cellular growth control. In this review, we discuss the evolution, structure, and regulation of the AMPK and TOR pathways and the complex mechanisms by which they interact.}, } @article {pmid32130562, year = {2020}, author = {Lashkarinia, SS and Çoban, G and Ermek, E and Çelik, M and Pekkan, K}, title = {Spatiotemporal remodeling of embryonic aortic arch: stress distribution, microstructure, and vascular growth in silico.}, journal = {Biomechanics and modeling in mechanobiology}, volume = {19}, number = {5}, pages = {1897-1915}, doi = {10.1007/s10237-020-01315-6}, pmid = {32130562}, issn = {1617-7940}, support = {307460/ERC_/European Research Council/International ; }, mesh = {Animals ; Aorta, Thoracic/*anatomy & histology/*embryology ; Chickens ; Collagen Type I/metabolism ; *Computer Simulation ; Finite Element Analysis ; Imaging, Three-Dimensional ; *Models, Anatomic ; Pressure ; Reproducibility of Results ; Stress, Mechanical ; }, abstract = {The microstructure for mature vessels has been investigated in detail, while there is limited information about the embryonic stages, in spite of their importance in the prognosis of congenital heart defects. It is hypothesized that the embryonic vasculature represents a disorganized but dynamic soft tissue, which rapidly evolves toward a specialized multi-cellular vascular structure under mechanical loading. Here the microstructural evolution process of the embryonic pharyngeal aortic arch structure was simulated using an in ovo validated long-term growth and remodeling computational model, implemented as an in-house FEBio plug-in. Optical coherence tomography-guided servo-null pressure measurements are assigned as boundary conditions through the critical embryonic stages. The accumulation of key microstructural constituents was recorded through zoom confocal microscopy for all six embryonic arch arteries simultaneously. The total amount and the radial variation slope of the collagen along the arch wall thickness in different arch types and for different embryonic times, with different dimension scales, were normalized and compared statistically. The arch growth model shows that the stress levels around the lumen boundary increase from [Formula: see text] (Stage 18) to a level higher than [Formula: see text] (Stage 24), depending on matrix constituent production rates, while the homeostatic strain level is kept constant. The statistical tests show that although the total collagen levels differentiate among bilateral positions of the same arch, the shape coefficient of the matrix microstructural gradient changes with embryonic time, proving radial localization, in accordance with numerical model results. In vivo cell number (DAPI) and vascular endothelial growth factor distributions followed similar trends.}, } @article {pmid32130216, year = {2020}, author = {Ronquist, F and Forshage, M and Häggqvist, S and Karlsson, D and Hovmöller, R and Bergsten, J and Holston, K and Britton, T and Abenius, J and Andersson, B and Buhl, PN and Coulianos, CC and Fjellberg, A and Gertsson, CA and Hellqvist, S and Jaschhof, M and Kjærandsen, J and Klopfstein, S and Kobro, S and Liston, A and Meier, R and Pollet, M and Riedel, M and Roháček, J and Schuppenhauer, M and Stigenberg, J and Struwe, I and Taeger, A and Ulefors, SO and Varga, O and Withers, P and Gärdenfors, U}, title = {Completing Linnaeus's inventory of the Swedish insect fauna: Only 5,000 species left?.}, journal = {PloS one}, volume = {15}, number = {3}, pages = {e0228561}, pmid = {32130216}, issn = {1932-6203}, mesh = {Animals ; *Biodiversity ; *Censuses ; Diptera/classification ; Ecosystem ; Europe ; *Extinction, Biological ; Insecta/*classification ; Phylogeny ; Records ; Sweden ; }, abstract = {Despite more than 250 years of taxonomic research, we still have only a vague idea about the true size and composition of the faunas and floras of the planet. Many biodiversity inventories provide limited insight because they focus on a small taxonomic subsample or a tiny geographic area. Here, we report on the size and composition of the Swedish insect fauna, thought to represent roughly half of the diversity of multicellular life in one of the largest European countries. Our results are based on more than a decade of data from the Swedish Taxonomy Initiative and its massive inventory of the country's insect fauna, the Swedish Malaise Trap Project The fauna is considered one of the best known in the world, but the initiative has nevertheless revealed a surprising amount of hidden diversity: more than 3,000 new species (301 new to science) have been documented so far. Here, we use three independent methods to analyze the true size and composition of the fauna at the family or subfamily level: (1) assessments by experts who have been working on the most poorly known groups in the fauna; (2) estimates based on the proportion of new species discovered in the Malaise trap inventory; and (3) extrapolations based on species abundance and incidence data from the inventory. For the last method, we develop a new estimator, the combined non-parametric estimator, which we show is less sensitive to poor coverage of the species pool than other popular estimators. The three methods converge on similar estimates of the size and composition of the fauna, suggesting that it comprises around 33,000 species. Of those, 8,600 (26%) were unknown at the start of the inventory and 5,000 (15%) still await discovery. We analyze the taxonomic and ecological composition of the estimated fauna, and show that most of the new species belong to Hymenoptera and Diptera groups that are decomposers or parasitoids. Thus, current knowledge of the Swedish insect fauna is strongly biased taxonomically and ecologically, and we show that similar but even stronger biases have distorted our understanding of the fauna in the past. We analyze latitudinal gradients in the size and composition of known European insect faunas and show that several of the patterns contradict the Swedish data, presumably due to similar knowledge biases. Addressing these biases is critical in understanding insect biomes and the ecosystem services they provide. Our results emphasize the need to broaden the taxonomic scope of current insect monitoring efforts, a task that is all the more urgent as recent studies indicate a possible worldwide decline in insect faunas.}, } @article {pmid32122349, year = {2020}, author = {Gray, MW and Burger, G and Derelle, R and Klimeš, V and Leger, MM and Sarrasin, M and Vlček, Č and Roger, AJ and Eliáš, M and Lang, BF}, title = {The draft nuclear genome sequence and predicted mitochondrial proteome of Andalucia godoyi, a protist with the most gene-rich and bacteria-like mitochondrial genome.}, journal = {BMC biology}, volume = {18}, number = {1}, pages = {22}, pmid = {32122349}, issn = {1741-7007}, support = {MOP-4124//CIHR/Canada ; MOP-11212//CIHR/Canada ; }, mesh = {Cell Nucleus/genetics ; Eukaryota/*genetics ; *Genome, Mitochondrial ; Mitochondrial Proteins/*genetics/metabolism ; *Proteome ; }, abstract = {BACKGROUND: Comparative analyses have indicated that the mitochondrion of the last eukaryotic common ancestor likely possessed all the key core structures and functions that are widely conserved throughout the domain Eucarya. To date, such studies have largely focused on animals, fungi, and land plants (primarily multicellular eukaryotes); relatively few mitochondrial proteomes from protists (primarily unicellular eukaryotic microbes) have been examined. To gauge the full extent of mitochondrial structural and functional complexity and to identify potential evolutionary trends in mitochondrial proteomes, more comprehensive explorations of phylogenetically diverse mitochondrial proteomes are required. In this regard, a key group is the jakobids, a clade of protists belonging to the eukaryotic supergroup Discoba, distinguished by having the most gene-rich and most bacteria-like mitochondrial genomes discovered to date.

RESULTS: In this study, we assembled the draft nuclear genome sequence for the jakobid Andalucia godoyi and used a comprehensive in silico approach to infer the nucleus-encoded portion of the mitochondrial proteome of this protist, identifying 864 candidate mitochondrial proteins. The A. godoyi mitochondrial proteome has a complexity that parallels that of other eukaryotes, while exhibiting an unusually large number of ancestral features that have been lost particularly in opisthokont (animal and fungal) mitochondria. Notably, we find no evidence that the A. godoyi nuclear genome has or had a gene encoding a single-subunit, T3/T7 bacteriophage-like RNA polymerase, which functions as the mitochondrial transcriptase in all eukaryotes except the jakobids.

CONCLUSIONS: As genome and mitochondrial proteome data have become more widely available, a strikingly punctuate phylogenetic distribution of different mitochondrial components has been revealed, emphasizing that the pathways of mitochondrial proteome evolution are likely complex and lineage-specific. Unraveling this complexity will require comprehensive comparative analyses of mitochondrial proteomes from a phylogenetically broad range of eukaryotes, especially protists. The systematic in silico approach described here offers a valuable adjunct to direct proteomic analysis (e.g., via mass spectrometry), particularly in cases where the latter approach is constrained by sample limitation or other practical considerations.}, } @article {pmid32118486, year = {2020}, author = {Chen, CY and Nguyen, LT and Paoli, GC and Irwin, PL}, title = {The complex multicellular morphology of the food spoilage bacteria Brochothrix thermosphacta strains isolated from ground chicken.}, journal = {Canadian journal of microbiology}, volume = {66}, number = {4}, pages = {303-312}, doi = {10.1139/cjm-2019-0502}, pmid = {32118486}, issn = {1480-3275}, mesh = {Animals ; Brochothrix/classification/*growth & development/isolation & purification/metabolism ; Chickens/*microbiology ; Culture Media/chemistry/metabolism ; Food Contamination/analysis ; Meat/microbiology ; Temperature ; }, abstract = {Herein we describe a highly structured, filamentous growth phenotype displayed by an isolate of the food spoilage microorganism Brochothrix thermosphacta. The growth morphology of this B. thermosphacta strain (strain BII) was dependent on environmental factors such as the growth media, incubation temperatures, and the inoculum concentration. Inoculation of cultures in highly dilute suspensions resulted in the formation of isolated, tight aggregates resembling fungal growth in liquid media. This same strain also formed stable, mesh-like structures in 6-well tissue culture plates under specific growth conditions. The complex growth phenotype does not appear to be unique to strain BII but was common among B. thermosphacta strains isolated from chicken. Light and electron micrographs showed that the filaments of multiple BII cells can organize into complex, tertiary structures resembling multistranded cables. Time-lapse microscopy was employed to monitor the development of such aggregates over 18 h and revealed growth originating from short filaments into compact ball-like clusters that appeared fuzzy due to protruding filaments or cables. This report is the first to document this complex filamentous growth phenotype in a wild-type bacterial isolate of B. thermosphacta.}, } @article {pmid32117212, year = {2019}, author = {Bonsignore, P and Kuiper, JWP and Adrian, J and Goob, G and Hauck, CR}, title = {CEACAM3-A Prim(at)e Invention for Opsonin-Independent Phagocytosis of Bacteria.}, journal = {Frontiers in immunology}, volume = {10}, number = {}, pages = {3160}, pmid = {32117212}, issn = {1664-3224}, mesh = {Animals ; Bacteria/*immunology ; Biological Evolution ; Carcinoembryonic Antigen/*genetics/*immunology ; Humans ; Immunity, Innate/genetics/immunology ; Phagocytosis/*genetics/*immunology ; Primates ; }, abstract = {Phagocytosis is one of the key innate defense mechanisms executed by specialized cells in multicellular animals. Recent evidence suggests that a particular phagocytic receptor expressed by human polymorphonuclear granulocytes, the carcinoembryonic antigen-related cell adhesion molecule 3 (CEACAM3), is one of the fastest-evolving human proteins. In this focused review, we will try to resolve the conundrum why a conserved process such as phagocytosis is conducted by a rapidly changing receptor. Therefore, we will first summarize the biochemical and structural details of this immunoglobulin-related glycoprotein in the context of the human CEACAM family. The function of CEACAM3 for the efficient, opsonin-independent detection and phagocytosis of highly specialized, host-restricted bacteria will be further elaborated. Taking into account the decisive role of CEACAM3 in the interaction with pathogenic bacteria, we will discuss the evolutionary trajectory of the CEACAM3 gene within the primate lineage and highlight the consequences of CEACAM3 polymorphisms in human populations. From a synopsis of these studies, CEACAM3 emerges as an important component of human innate immunity and a prominent example of a dedicated receptor for professional phagocytosis.}, } @article {pmid32115438, year = {2020}, author = {Urayama, SI and Takaki, Y and Hagiwara, D and Nunoura, T}, title = {dsRNA-seq Reveals Novel RNA Virus and Virus-Like Putative Complete Genome Sequences from Hymeniacidon sp. Sponge.}, journal = {Microbes and environments}, volume = {35}, number = {2}, pages = {}, pmid = {32115438}, issn = {1347-4405}, mesh = {Animals ; Aquatic Organisms/virology ; *Genome, Viral ; Phylogeny ; Porifera/*virology ; RNA Viruses/*classification/isolation & purification ; RNA, Double-Stranded/*genetics ; RNA, Viral/genetics ; RNA-Seq ; Sequence Analysis, DNA ; }, abstract = {Invertebrates are a source of previously unknown RNA viruses that fill gaps in the viral phylogenetic tree. Although limited information is currently available on RNA viral diversity in the marine sponge, a primordial multicellular animal that belongs to the phylum Porifera, the marine sponge is one of the well-studied holobiont systems. In the present study, we elucidated the putative complete genome sequences of five novel RNA viruses from Hymeniacidon sponge using a combination of double-stranded RNA sequencing, called fragmented and primer ligated dsRNA sequencing, and a conventional transcriptome method targeting single-stranded RNA. We identified highly diverged RNA-dependent RNA polymerase sequences, including a potential novel RNA viral lineage, in the sponge and three viruses presumed to infect sponge cells.}, } @article {pmid32109395, year = {2020}, author = {Tan, Y and Barnbrook, M and Wilson, Y and Molnár, A and Bukys, A and Hudson, A}, title = {Shared Mutations in a Novel Glutaredoxin Repressor of Multicellular Trichome Fate Underlie Parallel Evolution of Antirrhinum Species.}, journal = {Current biology : CB}, volume = {30}, number = {8}, pages = {1357-1366.e4}, doi = {10.1016/j.cub.2020.01.060}, pmid = {32109395}, issn = {1879-0445}, support = {BB/J01446X/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Antirrhinum/*genetics/growth & development ; *Biological Evolution ; Glutaredoxins/antagonists & inhibitors/*genetics ; Mutation ; Plant Proteins/antagonists & inhibitors/*genetics ; Trichomes/genetics/*growth & development ; }, abstract = {Most angiosperms produce trichomes-epidermal hairs that have protective or more specialized roles. Trichomes are multicellular in almost all species and, in the majority, secretory. Despite the importance of multicellular trichomes for plant protection and as a source of high-value products, the mechanisms that control their development are only poorly understood. Here, we investigate the control of multicellular trichome patterns using natural variation within the genus Antirrhinum (snapdragons), which has evolved hairy alpine-adapted species or lowland species with a restricted trichome pattern multiple times in parallel. We find that a single gene, Hairy (H), which is needed to repress trichome fate, underlies variation in trichome patterns between all Antirrhinum species except one. We show that H encodes a novel epidermis-specific glutaredoxin and that the pattern of trichome distribution within individuals reflects the location of H expression. Phylogenetic and functional tests suggest that H gained its trichome-repressing role late in the history of eudicots and that the ancestral Antirrhinum had an active H gene and restricted trichome distribution. Loss of H function was involved in an early divergence of alpine and lowland Antirrhinum lineages, and the alleles underlying this split were later reused in parallel evolution of alpines from lowland ancestors, and vice versa. We also find evidence for an evolutionary reversal from a widespread to restricted trichome distribution involving a suppressor mutation and for a pleiotropic effect of H on plant growth that might constrain the evolution of trichome pattern.}, } @article {pmid32102937, year = {2020}, author = {Elliott, L and Moore, I and Kirchhelle, C}, title = {Spatio-temporal control of post-Golgi exocytic trafficking in plants.}, journal = {Journal of cell science}, volume = {133}, number = {4}, pages = {}, doi = {10.1242/jcs.237065}, pmid = {32102937}, issn = {1477-9137}, support = {BB/P01979X/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Eukaryotic Cells/metabolism ; *Golgi Apparatus/metabolism ; *Plants/metabolism ; Protein Transport ; rab GTP-Binding Proteins/metabolism ; }, abstract = {A complex and dynamic endomembrane system is a hallmark of eukaryotic cells and underpins the evolution of specialised cell types in multicellular organisms. Endomembrane system function critically depends on the ability of the cell to (1) define compartment and pathway identity, and (2) organise compartments and pathways dynamically in space and time. Eukaryotes possess a complex molecular machinery to control these processes, including small GTPases and their regulators, SNAREs, tethering factors, motor proteins, and cytoskeletal elements. Whereas many of the core components of the eukaryotic endomembrane system are broadly conserved, there have been substantial diversifications within different lineages, possibly reflecting lineage-specific requirements of endomembrane trafficking. This Review focusses on the spatio-temporal regulation of post-Golgi exocytic transport in plants. It highlights recent advances in our understanding of the elaborate network of pathways transporting different cargoes to different domains of the cell surface, and the molecular machinery underpinning them (with a focus on Rab GTPases, their interactors and the cytoskeleton). We primarily focus on transport in the context of growth, but also highlight how these pathways are co-opted during plant immunity responses and at the plant-pathogen interface.}, } @article {pmid32095969, year = {2020}, author = {Moody, LA}, title = {Three-dimensional growth: a developmental innovation that facilitated plant terrestrialization.}, journal = {Journal of plant research}, volume = {133}, number = {3}, pages = {283-290}, pmid = {32095969}, issn = {1618-0860}, support = {BB/M020517/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {*Biological Evolution ; Chlorophyta/classification/*growth & development ; Embryophyta/classification/*growth & development ; Flowers ; Phaeophyta/classification/growth & development ; *Phylogeny ; Plant Roots ; }, abstract = {One of the most transformative events in the history of life on earth was the transition of plants from water to land approximately 470 million years ago. Within the Charophyte green algae, the closest living relatives of land plants, body plans have evolved from those that comprise simple unicells to those that are morphologically complex, large and multicellular. The Charophytes developed these broad ranging body plans by exploiting a range of one-dimensional and two-dimensional growth strategies to produce filaments, mats and branches. When plants were confronted with harsh conditions on land, they were required to make significant changes to the way they shaped their body plans. One of the fundamental developmental transitions that occurred was the evolution of three-dimensional growth and the acquisition of apical cells with three or more cutting faces. Plants subsequently developed a range of morphological adaptations (e.g. vasculature, roots, flowers, seeds) that enabled them to colonise progressively drier environments. 3D apical growth also evolved convergently in the brown algae, completely independently of the green lineage. This review summarises the evolving developmental complexities observed in the early divergent Charophytes all the way through to the earliest conquerors of land, and investigates 3D apical growth in the brown algae.}, } @article {pmid32094536, year = {2020}, author = {Tang, Q and Pang, K and Yuan, X and Xiao, S}, title = {A one-billion-year-old multicellular chlorophyte.}, journal = {Nature ecology & evolution}, volume = {4}, number = {4}, pages = {543-549}, pmid = {32094536}, issn = {2397-334X}, support = {80NSSC18K1086/ImNASA/Intramural NASA/United States ; }, mesh = {*Diatoms ; *Ecosystem ; Fossils ; Phylogeny ; }, abstract = {Chlorophytes (representing a clade within the Viridiplantae and a sister group of the Streptophyta) probably dominated marine export bioproductivity and played a key role in facilitating ecosystem complexity before the Mesozoic diversification of phototrophic eukaryotes such as diatoms, coccolithophorans and dinoflagellates. Molecular clock and biomarker data indicate that chlorophytes diverged in the Mesoproterozoic or early Neoproterozoic, followed by their subsequent phylogenetic diversification, multicellular evolution and ecological expansion in the late Neoproterozoic and Palaeozoic. This model, however, has not been rigorously tested with palaeontological data because of the scarcity of Proterozoic chlorophyte fossils. Here we report abundant millimetre-sized, multicellular and morphologically differentiated macrofossils from rocks approximately 1,000 million years ago. These fossils are described as Proterocladus antiquus new species and are interpreted as benthic siphonocladalean chlorophytes, suggesting that chlorophytes acquired macroscopic size, multicellularity and cellular differentiation nearly a billion years ago, much earlier than previously thought.}, } @article {pmid32094163, year = {2020}, author = {Yahalomi, D and Atkinson, SD and Neuhof, M and Chang, ES and Philippe, H and Cartwright, P and Bartholomew, JL and Huchon, D}, title = {A cnidarian parasite of salmon (Myxozoa: Henneguya) lacks a mitochondrial genome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {117}, number = {10}, pages = {5358-5363}, pmid = {32094163}, issn = {1091-6490}, mesh = {Animals ; *Genome, Mitochondrial ; *Host-Parasite Interactions ; Myxozoa/*classification/*genetics ; Phylogeny ; Salmon/*parasitology ; }, abstract = {Although aerobic respiration is a hallmark of eukaryotes, a few unicellular lineages, growing in hypoxic environments, have secondarily lost this ability. In the absence of oxygen, the mitochondria of these organisms have lost all or parts of their genomes and evolved into mitochondria-related organelles (MROs). There has been debate regarding the presence of MROs in animals. Using deep sequencing approaches, we discovered that a member of the Cnidaria, the myxozoan Henneguya salminicola, has no mitochondrial genome, and thus has lost the ability to perform aerobic cellular respiration. This indicates that these core eukaryotic features are not ubiquitous among animals. Our analyses suggest that H. salminicola lost not only its mitochondrial genome but also nearly all nuclear genes involved in transcription and replication of the mitochondrial genome. In contrast, we identified many genes that encode proteins involved in other mitochondrial pathways and determined that genes involved in aerobic respiration or mitochondrial DNA replication were either absent or present only as pseudogenes. As a control, we used the same sequencing and annotation methods to show that a closely related myxozoan, Myxobolus squamalis, has a mitochondrial genome. The molecular results are supported by fluorescence micrographs, which show the presence of mitochondrial DNA in M. squamalis, but not in H. salminicola. Our discovery confirms that adaptation to an anaerobic environment is not unique to single-celled eukaryotes, but has also evolved in a multicellular, parasitic animal. Hence, H. salminicola provides an opportunity for understanding the evolutionary transition from an aerobic to an exclusive anaerobic metabolism.}, } @article {pmid32084159, year = {2020}, author = {Finoshin, AD and Adameyko, KI and Mikhailov, KV and Kravchuk, OI and Georgiev, AA and Gornostaev, NG and Kosevich, IA and Mikhailov, VS and Gazizova, GR and Shagimardanova, EI and Gusev, OA and Lyupina, YV}, title = {Iron metabolic pathways in the processes of sponge plasticity.}, journal = {PloS one}, volume = {15}, number = {2}, pages = {e0228722}, pmid = {32084159}, issn = {1932-6203}, mesh = {Animals ; Computational Biology ; Gene Expression Profiling ; Iron/*metabolism ; Iron-Regulatory Proteins/genetics/metabolism ; Molecular Sequence Annotation ; Phylogeny ; Porifera/genetics/*metabolism ; RNA-Seq ; }, abstract = {The ability to regulate oxygen consumption evolved in ancestral animals and is intrinsically linked to iron metabolism. The iron pathways have been intensively studied in mammals, whereas data on distant invertebrates are limited. Sea sponges represent the oldest animal phylum and have unique structural plasticity and capacity to reaggregate after complete dissociation. We studied iron metabolic factors and their expression during reaggregation in the White Sea cold-water sponges Halichondria panicea and Halisarca dujardini. De novo transcriptomes were assembled using RNA-Seq data, and evolutionary trends were analyzed with bioinformatic tools. Differential expression during reaggregation was studied for H. dujardini. Enzymes of the heme biosynthesis pathway and transport globins, neuroglobin (NGB) and androglobin (ADGB), were identified in sponges. The globins mutate at higher evolutionary rates than the heme synthesis enzymes. Highly conserved iron-regulatory protein 1 (IRP1) presumably interacts with the iron-responsive elements (IREs) found in mRNAs of ferritin (FTH1) and a putative transferrin receptor NAALAD2. The reaggregation process is accompanied by increased expression of IRP1, the antiapoptotic factor BCL2, the inflammation factor NFκB (p65), FTH1 and NGB, as well as by an increase in mitochondrial density. Our data indicate a complex mechanism of iron regulation in sponge structural plasticity and help to better understand general mechanisms of morphogenetic processes in multicellular species.}, } @article {pmid32079678, year = {2020}, author = {Erwin, DH}, title = {The origin of animal body plans: a view from fossil evidence and the regulatory genome.}, journal = {Development (Cambridge, England)}, volume = {147}, number = {4}, pages = {}, doi = {10.1242/dev.182899}, pmid = {32079678}, issn = {1477-9129}, mesh = {Animals ; Biological Evolution ; *Body Patterning ; Cell Differentiation ; Embryo, Nonmammalian ; *Fossils ; Gene Regulatory Networks ; *Genome ; Genomics ; Invertebrates/classification ; Paleontology ; Phylogeny ; *Regulatory Sequences, Nucleic Acid ; Sequence Analysis, RNA ; }, abstract = {The origins and the early evolution of multicellular animals required the exploitation of holozoan genomic regulatory elements and the acquisition of new regulatory tools. Comparative studies of metazoans and their relatives now allow reconstruction of the evolution of the metazoan regulatory genome, but the deep conservation of many genes has led to varied hypotheses about the morphology of early animals and the extent of developmental co-option. In this Review, I assess the emerging view that the early diversification of animals involved small organisms with diverse cell types, but largely lacking complex developmental patterning, which evolved independently in different bilaterian clades during the Cambrian Explosion.}, } @article {pmid32078984, year = {2020}, author = {Moreau, CS}, title = {Symbioses among ants and microbes.}, journal = {Current opinion in insect science}, volume = {39}, number = {}, pages = {1-5}, doi = {10.1016/j.cois.2020.01.002}, pmid = {32078984}, issn = {2214-5753}, mesh = {Animals ; *Ants/microbiology/parasitology ; Bacteria ; Behavior ; Diet ; Fungi ; Gastrointestinal Microbiome ; Host-Parasite Interactions ; Microbiota ; Nematoda ; *Symbiosis ; Trematoda ; Viruses ; }, abstract = {Ants have been shown to engage in symbiosis across the tree of life, although our knowledge is far from complete. These interactions range from mutualistic to parasitic with several instances of manipulation of host behavior. Nutrient contributions in these symbioses include both farming for food and nitrogen recycling by gut-associated microbes. Interestingly, the ants that are mostly likely to host diverse and likely functional gut microbial communities are those that feed on extreme diets. Although we do see many instances of symbiosis between ants and microbes, there are also examples of species without a functional gut microbiome. Symbiosis among microbes and eukaryotic hosts is common and often considered a hallmark of multicellular evolution [1]. This is true among many of the over 13000 species of ants, although symbiosis between ants and microbes are not ubiquitous. These microbial-ant symbiotic interactions span the tree of life and include microbial eukaryotes, fungi, viruses, and bacteria. These interactions range from pathogenic to mutualistic, with many relationships still not well understood. Although our knowledge of the diversity of these microbes in ants is growing rapidly, and in some cases we know the function and interaction with the host, we still have much to learn about - the little things that run the little things that run the world!}, } @article {pmid32075388, year = {2020}, author = {Raudenská, M and Svobodová, M and Gumulec, J and Falk, M and Masařík, M}, title = {The Importance of Cancer-Associated Fibroblasts in the Pathogenesis of Head and Neck Cancers.}, journal = {Klinicka onkologie : casopis Ceske a Slovenske onkologicke spolecnosti}, volume = {33}, number = {1}, pages = {39-48}, doi = {10.14735/amko202039}, pmid = {32075388}, issn = {1802-5307}, mesh = {*Cancer-Associated Fibroblasts ; Head and Neck Neoplasms/*pathology ; Humans ; Phenotype ; }, abstract = {BACKGROUND: Despite progress in anticancer therapies, head and neck squamous cell carcinoma (HNSCC) has still a low survival rate. Recent studies have shown that tumour stroma may play an important role in the pathogenesis of this malignant disease. Fibroblasts are a major component of the tumour microenvironment and may significantly influence HNSCC progression as indicated by the contribution they make to important hallmarks of cancer, such as inflammation, non-restricted growth, angiogenesis, invasion, metastasis, and therapy resistance. It is well known that tumour cells can confer a cancer-associated fibroblast (CAF) phenotype that supports the growth and dissemination of cancer cells. CAFs can stimulate cancer progression through cell-cell contacts and communication, remodelling of extracellular matrix, and production of many signal molecules and matrix metalloproteinases. Consequently, genetic changes in epithelial cells