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Bibliography on: Mitochondrial Evolution

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ESP: PubMed Auto Bibliography 15 Nov 2018 at 01:41 Created: 

Mitochondrial Evolution

The endosymbiotic hypothesis for the origin of mitochondria (and chloroplasts) suggests that mitochondria are descended from specialized bacteria (probably purple nonsulfur bacteria) that somehow survived endocytosis by another species of prokaryote or some other cell type, and became incorporated into the cytoplasm.

Created with PubMed® Query: mitochondria AND evolution NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)

RevDate: 2018-11-13

Patten MM (2018)

The X chromosome favors males under sexually antagonistic selection.

Evolution; international journal of organic evolution [Epub ahead of print].

The X chromosome is found twice as often in females as males. This has led to an intuition that X-linked genes for traits experiencing sexually antagonistic selection should tend to evolve toward the female optimum. However, this intuition has never been formally examined. In this paper, I present a simple mathematical model and ask whether the X chromosome is indeed biased toward effecting female-optimal phenotypes. Counter to the intuition, I find that the exact opposite bias exists; the X chromosome is revealed to be a welcome spot for mutations that benefit males at the expense of females. Not only do male-beneficial alleles have an easier time of invading and spreading through a population, but they also achieve higher equilibrium frequencies than comparable female-beneficial alleles. The X chromosome is therefore expected over evolutionary time to nudge phenotypes closer to the male optimum. Consequently, the X chromosome should find itself engaged in perpetual intragenomic conflicts with the autosomes and the mitochondria over developmental outcomes. The X chromosome's male bias and the intragenomic conflicts that ensue bear on the evolution of gene regulation, speciation, and our concept of organismality. This article is protected by copyright. All rights reserved.

RevDate: 2018-11-12

Muthye V, DV Lavrov (2018)

Characterization of mitochondrial proteomes of nonbilaterian animals.

IUBMB life [Epub ahead of print].

Mitochondria require ~1,500 proteins for their maintenance and proper functionality, which constitute the mitochondrial proteome (mt-proteome). Although a few of these proteins, mostly subunits of the electron transport chain complexes, are encoded in mitochondrial DNA (mtDNA), the vast majority are encoded in the nuclear genome and imported to the organelle. Previous studies have shown a continuous and complex evolution of mt-proteome among eukaryotes. However, there was less attention paid to mt-proteome evolution within Metazoa, presumably because animal mtDNA and, by extension, animal mitochondria are often considered to be uniform. In this analysis, two bioinformatic approaches (Orthologue-detection and Mitochondrial Targeting Sequence prediction) were used to identify mt-proteins in 23 species from four nonbilaterian phyla: Cnidaria, Ctenophora, Placozoa, and Porifera, as well as two choanoflagellates, the closest animal relatives. Our results revealed a large variation in mt-proteome in nonbilaterian animals in size and composition. Myxozoans, highly reduced cnidarian parasites, possessed the smallest inferred mitochondrial proteomes, while calcareous sponges possessed the largest. About 513 mitochondrial orthologous groups were present in all nonbilaterian phyla and human. Interestingly, 42 human mitochondrial proteins were not identified in any nonbilaterian species studied and represent putative innovations along the bilaterian branch. Several of these proteins were involved in apoptosis and innate immunity, two processes known to evolve within Metazoa. Conversely, several proteins identified as mitochondrial in nonbilaterian phyla and animal outgroups were absent in human, representing cases of possible loss. Finally, a few human cytosolic proteins, such as histones and cytosolic ribosomal proteins, were predicted to be targeted to mitochondria in nonbilaterian animals. Overall, our analysis provides the first step in characterization of mt-proteomes in nonbilaterian animals and understanding evolution of animal mt-proteome. © 2018 IUBMB Life, 2018.

RevDate: 2018-11-12

Lasne C, Van Heerwaarden B, Sgrò CM, et al (2018)

Quantifying the relative contributions of the X chromosome, autosomes and mitochondrial genome to local adaptation.

Evolution; international journal of organic evolution [Epub ahead of print].

During local adaptation with gene flow, some regions of the genome are inherently more responsive to selection than others. Recent theory predicts that X-linked genes should disproportionately contribute to local adaptation relative to other genomic regions, yet this prediction remains to be tested. We carried out a multi-generation crossing scheme, using two cline-end populations of Drosophila melanogaster, to estimate the relative contributions of the X chromosome, autosomes and mitochondrial genome to adaptive divergence in four traits involved in local adaptation (wing size, and resistance to heat, desiccation, and starvation stresses). We found that the mitochondrial genome and autosomes contributed significantly to clinal divergence in three of the four traits. In contrast, the X made no significant contribution to divergence in these traits. Given the small size of the mitochondrial genome, our results indicate that it plays a surprisingly large role in clinal adaptation. In contrast, the X, which represents roughly 20% of the Drosophila genome, contributes negligibly - a pattern that conflicts with theoretical predictions. These patterns reinforce recent work implying a central role of mitochondria in climatic adaptation, and suggest that different genomic regions may play fundamentally different roles in processes of divergence with gene flow. This article is protected by copyright. All rights reserved.

RevDate: 2018-11-09
CmpDate: 2018-11-09

Gao XM, Mu DL, Hou CC, et al (2019)

Expression and putative functions of KIFC1 for nuclear reshaping and midpiece formation during spermiogenesis of Phascolosoma esculenta.

Gene, 683:169-183.

Kinesin-14 KIFC1 plays an important role in vesicular transport, microtubule organization, and spermiogenesis. In this study, we first investigated the microtubule distribution and expression pattern of KIFC1 during spermiogenesis of P. esculenta. Microtubules are abundant during spermiogenesis of P. esculenta and may be related to the generation and maintenance of pseudopodia-like cytoplasmic protrusions and nuclear reshaping. The Pe-KIFC1 protein is conserved with a motor domain where microtubule and ATP binding sites are predicted, a coiled-coil domain and a divergent tail domain. The Pe-kifc1 gene was extensively expressed and showed the highest expression in coelomic fluid where spermiogenesis occurs. We further observed the expression of kifc1 mRNA and protein and found that Pe-KIFC1 protein primarily co-localized with microtubules during spermiogenesis, indicating that KIFC1 might play several roles during this process via its cargo transport and/or microtubule organization function. In addition, co-localization of mitochondria and KIFC1 was also detected during spermiogenesis, which were located in the midpiece in mature sperm, suggesting that mitochondria might be a cargo of Pe-KIFC1 that participates in the intracellular distribution of mitochondria and formation of the midpiece. Based on our detailed observations of the dynamic distribution of microtubules, KIFC1, and mitochondria during spermiogenesis and the conserved function of KIFC1 in cargo transport and microtubule organization, functional models of Pe-KIFC1 during spermiogenesis are proposed, including the participation of KIFC1 in nuclear reshaping and midpiece formation.

RevDate: 2018-11-08
CmpDate: 2018-11-08

Chang CH, Dai WY, Chen TY, et al (2018)

DNA barcoding reveals CITES-listed species among Taiwanese government-seized chelonian specimens.

Genome, 61(8):615-624.

Compared to traditional morphological identification, DNA barcoding-molecular identification based on sequencing of a segment of mitochondrial cytochrome c oxidase subunit I (COI)-provides a shortcut to authenticating chelonian identifications. Here, we selected 63 government-seized chelonian specimens deposited at Taipei Zoo for DNA barcoding analysis. DNA barcoding and subsequent phylogenetic analysis successfully authenticated 36 chelonian species, including five that are listed in CITES Appendix I. Approximately 90% (57/63) of the specimens were successfully authenticated by our molecular approach, but lack or error of BOLD reference sequences, biological processes such as hybridization, and uncertain species delimitation all reduced the accuracy of DNA barcoding. To increase the accuracy of DNA barcoding, Taipei Zoo will continue to enrich the BOLD database and also establish a genetic database, to include additional genetic markers, by using government-seized chelonian specimens. A fast and accurate method to authenticate seized samples could assist law enforcement agencies to prosecute criminals and restrict illegal exploitation of wild chelonian resources.

RevDate: 2018-11-08
CmpDate: 2018-11-08

Wilkerson CD, Mahoney SP, SM Carr (2018)

Post-glacial recolonization of insular Newfoundland across the Strait of Belle Isle gave rise to an endemic subspecies of woodland caribou, Rangifer tarandus terranovae (Bangs, 1896): evidence from mtDNA haplotypes.

Genome, 61(8):575-585.

Post-glacial origins of woodland caribou (Rangifer tarandus subsp.) on the island of Newfoundland and their relationship to mainland populations have been uncertain. Sequence analysis of 2223 bp of the mitochondrial DNA control region and cytochrome b gene from 233 Newfoundland caribou identified 32 haplotypes in four major clades. Comparison with other Nearctic caribou confirms a closer affinity of the basal Clade A with animals from the mainland, and as an outgroup to Clades B, C, and D that are endemic to the island. This indicates re-entry of caribou to post-glacial Newfoundland across the Strait of Belle Isle from Labrador, rather than from southern coastal refugia. Newfoundland caribou are a distinct subspecies, Rangifer tarandus terranovae (Bangs, 1896). Hierarchical AMOVA shows significant clinal differentiation of the major clades from northwest to southeast across the island. The isolated Avalon Peninsula population in the extreme southeast is genetically depauperate. Founder effects are evident in herds introduced to previously unoccupied areas by wildlife managers over the past 40-50 years. Reindeer introduced in the early 20th century have not contributed to mtDNA diversity in Newfoundland caribou.

RevDate: 2018-11-08
CmpDate: 2018-11-08

Ries LNA, José de Assis L, Rodrigues FJS, et al (2018)

The Aspergillus nidulans Pyruvate Dehydrogenase Kinases Are Essential To Integrate Carbon Source Metabolism.

G3 (Bethesda, Md.), 8(7):2445-2463 pii:g3.118.200411.

The pyruvate dehydrogenase complex (PDH), that converts pyruvate to acetyl-coA, is regulated by pyruvate dehydrogenase kinases (PDHK) and phosphatases (PDHP) that have been shown to be important for morphology, pathogenicity and carbon source utilization in different fungal species. The aim of this study was to investigate the role played by the three PDHKs PkpA, PkpB and PkpC in carbon source utilization in the reference filamentous fungus Aspergillus nidulans, in order to unravel regulatory mechanisms which could prove useful for fungal biotechnological and biomedical applications. PkpA and PkpB were shown to be mitochondrial whereas PkpC localized to the mitochondria in a carbon source-dependent manner. Only PkpA was shown to regulate PDH activity. In the presence of glucose, deletion of pkpA and pkpC resulted in reduced glucose utilization, which affected carbon catabolite repression (CCR) and hydrolytic enzyme secretion, due to de-regulated glycolysis and TCA cycle enzyme activities. Furthermore, PkpC was shown to be required for the correct metabolic utilization of cellulose and acetate. PkpC negatively regulated the activity of the glyoxylate cycle enzyme isocitrate lyase (ICL), required for acetate metabolism. In summary, this study identified PDHKs important for the regulation of central carbon metabolism in the presence of different carbon sources, with effects on the secretion of biotechnologically important enzymes and carbon source-related growth. This work demonstrates how central carbon metabolism can affect a variety of fungal traits and lays a basis for further investigation into these characteristics with potential interest for different applications.

RevDate: 2018-11-08
CmpDate: 2018-11-08

Kramer P, P Bressan (2018)

Our (Mother's) Mitochondria and Our Mind.

Perspectives on psychological science : a journal of the Association for Psychological Science, 13(1):88-100.

Most of the energy we get to spend is furnished by mitochondria, minuscule living structures sitting inside our cells or dispatched back and forth within them to where they are needed. Mitochondria produce energy by burning down what remains of our meal after we have digested it, but at the cost of constantly corroding themselves and us. Here we review how our mitochondria evolved from invading bacteria and have retained a small amount of independence from us; how we inherit them only from our mother; and how they are heavily implicated in learning, memory, cognition, and virtually every mental or neurological affliction. We discuss why counteracting mitochondrial corrosion with antioxidant supplements is often unwise, and why our mitochondria, and therefore we ourselves, benefit instead from exercise, meditation, sleep, sunshine, and particular eating habits. Finally, we describe how malfunctioning mitochondria force rats to become socially subordinate to others, how such disparity can be evened off by a vitamin, and why these findings are relevant to us.

RevDate: 2018-11-08
CmpDate: 2018-11-08

Shen CM, Hu L, Yang CH, et al (2017)

Genetic polymorphisms of 54 mitochondrial DNA SNP loci in Chinese Xibe ethnic minority group.

Scientific reports, 7:44407 pii:srep44407.

We analyzed the genetic polymorphisms of 54 mitochondrial DNA (mtDNA) variants in Chinese Xibe ethnic minority group. A total of 137 unrelated healthy volunteers from Chinese Xibe group were the objects of our study. Among the selected loci, there were 51 variable positions including transitions and transversions, and single nucleotide transitions were common (83.93%) versus transversions. These variations defined 64 different mtDNA haplotypes exclusive of (CA)n and 9 bp deletion variation. The haplotype diversity and discrimination power in Xibe population were 0.9800 ± 0.004 and 0.9699, respectively. Besides, we compared Xibe group with 18 other populations and reconstructed a phylogenetic tree using Neighbor-Joining method. The result revealed that Xibe group was a close to Xinjiang Han and Yanbian Korean groups. Our data also indicated that Xibe group has a close relationship with Daur and Ewenki groups, which is reflected by the history that Xibe was influenced by Daur and Ewenki groups during the development of these groups. In conclusion, the variants we studied are polymorphic and could be used as informative genetic markers for forensic and population genetic application.

RevDate: 2018-11-05

Fan PC, Zhang Y, Wang Y, et al (2018)

Quantitative proteomics reveals mitochondrial respiratory chain as a dominant target for carbon ion radiation: delayed reactive oxygen species generation caused DNA damage.

Free radical biology & medicine pii:S0891-5849(18)32297-4 [Epub ahead of print].

Heavy ion radiotherapy has shown great promise for cancer therapy. Understanding the cellular response mechanism to heavy ion radiation is required to explore measures of overcoming devastating side effects. Here, we performed a quantitative proteomic analysis to investigate the mechanism of carbon ion irradiation on human AHH-1 lymphoblastoid cells. We identified 4602 proteins and quantified 4569 proteins showing high coverage in the mitochondria. Data are available via ProteomeXchange with identifier PXD008351. After stringent filtering, 290 proteins were found to be significantly up-regulated and 16 proteins were down-regulated. Functional analysis revealed that these up-regulated proteins were enriched in the process of DNA damage repair, mitochondrial ribosome, and particularly mitochondrial respiratory chain, accounting for approximately 50% of the accumulated proteins. Bioinformatics and functional analysis demonstrated that these up-regulated mitochondrial respiratory chain proteins enhanced ATP production and simultaneously reactive oxygen species release. More importantly, increased reactive oxygen species led to secondary organelle injury and lagged DNA double-strand breaks. Consistently, the expression of antioxidant enzymes was up-regulated for free radical scavenging. The mechanism of lagged secondary injury originated from disturbances in the mitochondrial respiratory chain. Our results provided a novel target for cell self-repair against heavy ion radiation-induced cellular damage.

RevDate: 2018-11-05

Rand DM, Mossman JA, Zhu L, et al (2018)

Mitonuclear epistasis, genotype-by-environment interactions, and personalized genomics of complex traits in Drosophila.

IUBMB life [Epub ahead of print].

Mitochondrial function requires the coordinated expression of dozens of gene products from the mitochondrial genome and hundreds from the nuclear genomes. The systems that emerge from these interactions convert the food we eat and the oxygen we breathe into energy for life, while regulating a wide range of other cellular processes. These facts beg the question of whether the gene-by-gene interactions (G x G) that enable mitochondrial function are distinct from the gene-by-environment interactions (G x E) that fuel mitochondrial activity. We examine this question using a Drosophila model of mitonuclear interactions in which experimental combinations of mtDNA and nuclear chromosomes generate pairs of mitonuclear genotypes to test for epistatic interactions (G x G). These mitonuclear genotypes are then exposed to altered dietary or oxygen environments to test for G x E interactions. We use development time to assess dietary effects, and genome wide RNAseq analyses to assess hypoxic effects on transcription, which can be partitioned in to mito, nuclear, and environmental (G x G x E) contributions to these complex traits. We find that mitonuclear epistasis is universal, and that dietary and hypoxic treatments alter the epistatic interactions. We further show that the transcriptional response to alternative mitonuclear interactions has significant overlap with the transcriptional response to alternative oxygen environments. Gene coexpression analyses suggest that these shared genes are more central in networks of gene interactions, implying some functional overlap between epistasis and genotype by environment interactions. These results are discussed in the context of evolutionary fitness, the genetic basis of complex traits, and the challenge of achieving precision in personalized medicine. © 2018 IUBMB Life, :1-14, 2018.

RevDate: 2018-11-04

Xu L, Peng L, Gu T, et al (2018)

The 3'UTR of human MAVS mRNA contains multiple regulatory elements for the control of protein expression and subcellular localization.

Biochimica et biophysica acta. Gene regulatory mechanisms pii:S1874-9399(18)30242-6 [Epub ahead of print].

Post-transcriptional regulation controls the mRNA stability, translation efficiency, and subcellular localization of a protein. The mitochondrial antiviral signaling protein (MAVS) plays a vital role in innate antiviral immunity. The MAVS mRNA has a long 3' untranslated region (UTR, >9 kb) and an understanding of this region may help to explain the post-transcriptional regulation in a key protein. In this study, we aimed to characterize the role of the MAVS 3'UTR during MAVS expression by truncating the 3'UTR into different fragments so as to identify the regulatory elements. We found that the different fragments (H1-H5) of the MAVS 3'UTR play different roles in regulating the subcellular localization and function of MAVS. Three AU-rich elements (AREs) in the MAVS 3'UTR H1 fragment (region 1-3445 in the 3'UTR) repressed MAVS expression by interacting with HuR to destabilize its mRNA. The MAVS 3'UTR H5 fragment (region 5955-7687 in the 3'UTR) affected the cellular localization of MAVS in mitochondria and influenced the subsequent antiviral function. Four miR-27a binding sites were recognized in the MAVS 3'UTR, and treatment of miR-27a inhibited MAVS expression and promoted the replication of the vesicular stomatitis virus (VSV). The identification of multiple regulatory elements in the MAVS 3'UTR offers new insights into the precise control of MAVS expression in innate immunity.

RevDate: 2018-11-04

Portugez S, Martin WF, E Hazkani-Covo (2018)

Mosaic mitochondrial-plastid insertions into the nuclear genome show evidence of both non-homologous end joining and homologous recombination.

BMC evolutionary biology, 18(1):162 pii:10.1186/s12862-018-1279-x.

BACKGROUND: Mitochondrial and plastid DNA fragments are continuously transferred into eukaryotic nuclear genomes, giving rise to nuclear copies of mitochondrial DNA (numts) and nuclear copies of plastid DNA (nupts). Numts and nupts are classified as simple if they are composed of a single organelle fragment or as complex if they are composed of multiple fragments. Mosaic insertions are complex insertions composed of fragments of both mitochondrial and plastid DNA. Simple numts and nupts in eukaryotes have been extensively studied, their mechanism of insertion involves non-homologous end joining (NHEJ). Mosaic insertions have been less well-studied and their mechanisms of integration are unknown.

RESULTS: Here we estimated the number of nuclear mosaic insertions (numins) in nine plant genomes. We show that numins compose up to 10% of the total nuclear insertions of organelle DNA in these plant genomes. The NHEJ hallmarks typical for numts and nupts were also identified in mosaic insertions. However, the number of identified insertions that integrated via NHEJ mechanism is underestimated, as NHEJ signatures are conserved only in recent insertions and mutationally eroded in older ones. A few complex insertions show signatures of long homology that cannot be attributed to NHEJ, a novel observation that implicates gene conversion or single strand annealing mechanisms in organelle nuclear insertions.

CONCLUSIONS: The common NHEJ signature that was identified here reveals that, in plant cells, mitochondria and plastid fragments in numins must meet during or prior to integration into the nuclear genome.

RevDate: 2018-11-05
CmpDate: 2018-11-05

Godahewa GI, Perera NCN, Nam BH, et al (2018)

Antioxidative properties and structural features of atypical 2-Cys peroxiredoxin from Sebastes schlegelii.

Developmental and comparative immunology, 82:152-164.

Atypical 2-Cys peroxiredoxin (Prx5) is an antioxidant protein that exerts its antioxidant function by detoxifying different reactive oxygen species (ROS). Here, we identified mitochondrial Prx5 from rockfish (SsPrx5) and described its specific structural and functional characteristics. The open reading frame (ORF) of SsPrx5 (570 bp) was translated into a 190-amino acid polypeptide that contained a mitochondrial targeting sequence (MTS), thioredoxin 2 domain, two Prx-specific signature motifs, and three conserved cysteine residues. Sequence comparison indicated that the SsPrx5 protein sequence shared greatest identity with teleost orthologs, where the phylogenetic results showed an evolutionary position within the fish Prx5. The coding sequence of SsPrx5 was scattered in six exons as found in other vertebrates. Additionally, the potent antioxidant functions of recombinantly expressed SsPrx5 protein was demonstrated by insulin reduction and extracellular H2O2 scavenging both in vitro and in vivo. Quantitative real time PCR (qPCR) detected ubiquitous mRNA expression of SsPrx5 in healthy rockfish tissues, with remarkable expression observed in gill, liver, and reproductive tissues. Prompt transcription of SsPrx5 was shown in the immune-stimulated gill and liver tissues against Streptococcus iniae and lipopolysaccharide injection. Taken together, present results suggest the indispensable role of SsPrx5 in the rockfish antioxidant defense system against oxidative stresses and its role in maintaining redox balance upon pathogen invasion.

RevDate: 2018-11-02

Loell K, V Nanda (2018)

Marginal protein stability drives subcellular proteome isoelectric point.

Proceedings of the National Academy of Sciences of the United States of America pii:1809098115 [Epub ahead of print].

There exists a positive correlation between the pH of subcellular compartments and the median isoelectric point (pI) for the associated proteomes. Proteins in the human lysosome-a highly acidic compartment in the cell-have a median pI of ∼6.5, whereas proteins in the more basic mitochondria have a median pI of ∼8.0. Proposed mechanisms reflect potential adaptations to pH. For example, enzyme active site general acid/base residue pKs are likely evolved to match environmental pH. However, such effects would be limited to a few residues on specific proteins, and might not affect the proteome at large. A protein model that considers residue burial upon folding recapitulates the correlation between proteome pI and environmental pH. This correlation can be fully described by a neutral evolution process; no functional selection is included in the model. Proteins in acidic environments incur a lower energetic penalty for burying acidic residues than basic residues, resulting in a net accumulation of acidic residues in the protein core. The inverse is true under alkaline conditions. The pI distributions of subcellular proteomes are likely not a direct result of functional adaptations to pH, but a molecular spandrel stemming from marginal stability.

RevDate: 2018-11-02
CmpDate: 2018-11-02

Younas F, Soltanmohammadi N, Knapp O, et al (2018)

The major outer membrane protein of Legionella pneumophila Lpg1974 shows pore-forming characteristics similar to the human mitochondrial outer membrane pore, hVDAC1.

Biochimica et biophysica acta. Biomembranes, 1860(8):1544-1553.

Legionella pneumophila is an aerobic and nonspore-forming pathogenic Gram-negative bacterium of the genus Legionella. It is the causative agent of Legionnaires' disease, also known as Legionellosis. The hosts of this organism are diverse, ranging from simple water borne protozoans such as amoebae to more complex hosts such as macrophages in humans. Genome analyses have shown the presence of genes coding for eukaryotic like proteins in several Legionella species. The presence of these proteins may assist L. pneumophila in its adaptation to the eukaryotic host. We studied the characteristics of a protein (Lpg1974) of L. pneumophila that shows remarkable homologies in length of the primary sequence and for the identity/homology of many amino acids to the voltage dependent anion channel (human VDAC1, Porin 31HL) of human mitochondria. Two different forms of Lpg1974 were overexpressed in Escherichia coli and purified to homogeneity: the one containing a putative N-terminal signal sequence and one without it. Reconstituted protein containing the signal sequence formed ion-permeable pores in lipid bilayer membranes with a conductance of approximately 5.4 nS in 1 M KCl. When the predicted N-terminal signal peptide of Lpg1974 comprising an α-helical structure similar to that at the N-terminus of hVDAC1 was removed, the channels formed in reconstitution experiments had a conductance of 7.6 nS in 1 M KCl. Both Lpg1974 proteins formed pores that were voltage-dependent and anion-selective similar to the pores formed by hVDAC1. These results suggest that Lpg1974 of L. pneumophila is indeed a structural and functional homologue to hVDAC1.

RevDate: 2018-11-01
CmpDate: 2018-11-01

Tong W, He Q, YJ Park (2017)

Genetic variation architecture of mitochondrial genome reveals the differentiation in Korean landrace and weedy rice.

Scientific reports, 7:43327 pii:srep43327.

Mitochondrial genome variations have been detected despite the overall conservation of this gene content, which has been valuable for plant population genetics and evolutionary studies. Here, we describe mitochondrial variation architecture and our performance of a phylogenetic dissection of Korean landrace and weedy rice. A total of 4,717 variations across the mitochondrial genome were identified adjunct with 10 wild rice. Genetic diversity assessment revealed that wild rice has higher nucleotide diversity than landrace and/or weedy, and landrace rice has higher diversity than weedy rice. Genetic distance was suggestive of a high level of breeding between landrace and weedy rice, and the landrace showing a closer association with wild rice than weedy rice. Population structure and principal component analyses showed no obvious difference in the genetic backgrounds of landrace and weedy rice in mitochondrial genome level. Phylogenetic, population split, and haplotype network evaluations were suggestive of independent origins of the indica and japonica varieties. The origin of weedy rice is supposed to be more likely from cultivated rice rather than from wild rice in mitochondrial genome level.

RevDate: 2018-10-31

Gabaldón T (2018)

Evolution of the Peroxisomal Proteome.

Sub-cellular biochemistry, 89:221-233.

Peroxisomes are single-membrane bound intracellular organelles that can be found in organisms across the tree of eukaryotes, and thus are likely to derive from an ancestral peroxisome in the last eukaryotic common ancestor (LECA). Yet, peroxisomes in different lineages can present a large diversity in terms of their metabolic capabilities, which reflects a highly variable proteomic content. Theories on the evolutionary origin of peroxisomes have shifted in the last decades from scenarios involving an endosymbiotic origin, similar to those of mitochondria and plastids, towards hypotheses purporting an endogenous origin from within the endomembrane system. The peroxisomal proteome is highly dynamic in evolutionary terms, and can evolve via differential loss and gain of proteins, as well as via relocalization of proteins from and to other sub-cellular compartments. Here, I review current knowledge and discussions on the diversity, origin, and evolution of the peroxisomal proteome.

RevDate: 2018-10-31

Cai C, Liu F, Jiang T, et al (2018)

Comparative study on mitogenomes of green tide algae.

Genetica pii:10.1007/s10709-018-0046-7 [Epub ahead of print].

Since 2007, the annual green tide disaster in the Yellow Sea has brought serious economic losses to China. There is no research on the genetic similarities of four constituent species of green tide algae at the genomic level. We previously determined the mitochondrial genomes of Ulva prolifera, Ulva linza and Ulva flexuosa. In the present work, the mitochondrial genome of another green tide (Ulva compressa) was sequenced and analyzed. With the length of 62,311 bp, it contained 29 encoding genes, 26 tRNAs and 10 open reading frames. By comparing these four mitochondrial genomes, we found that U. compressa was quite different from the other three types of Ulva species. However, there were similarities between U. prolifera and U. linza in the number, distribution and homology of open reading frames, evolutionary and codon variation of tRNA, evolutionary relationship and selection pressure of coding genes. Repetitive sequence analysis of simple sequence repeats, tandem repeat and forward repeats further supposed that they have evolved from the same origin. In addition, we directly analyzed gene homologies and translocation of four green tide algae by Mauve alignment. There were gene order rearrangements among them. With fast-evolving genomes, these four green algal mitochondria have both conservatism and variation, thus opening another window for the understanding of origin and evolution of Ulva.

RevDate: 2018-10-31
CmpDate: 2018-10-31

Gandini CL, MV Sanchez-Puerta (2017)

Foreign Plastid Sequences in Plant Mitochondria are Frequently Acquired Via Mitochondrion-to-Mitochondrion Horizontal Transfer.

Scientific reports, 7:43402 pii:srep43402.

Angiosperm mitochondrial genomes (mtDNA) exhibit variable quantities of alien sequences. Many of these sequences are acquired by intracellular gene transfer (IGT) from the plastid. In addition, frequent events of horizontal gene transfer (HGT) between mitochondria of different species also contribute to their expanded genomes. In contrast, alien sequences are rarely found in plastid genomes. Most of the plant-to-plant HGT events involve mitochondrion-to-mitochondrion transfers. Occasionally, foreign sequences in mtDNAs are plastid-derived (MTPT), raising questions about their origin, frequency, and mechanism of transfer. The rising number of complete mtDNAs allowed us to address these questions. We identified 15 new foreign MTPTs, increasing significantly the number of those previously reported. One out of five of the angiosperm species analyzed contained at least one foreign MTPT, suggesting a remarkable frequency of HGT among plants. By analyzing the flanking regions of the foreign MTPTs, we found strong evidence for mt-to-mt transfers in 65% of the cases. We hypothesize that plastid sequences were initially acquired by the native mtDNA via IGT and then transferred to a distantly-related plant via mitochondrial HGT, rather than directly from a foreign plastid to the mitochondrial genome. Finally, we describe three novel putative cases of mitochondrial-derived sequences among angiosperm plastomes.

RevDate: 2018-10-30

Mehta AP, Supekova L, Chen JH, et al (2018)

Engineering yeast endosymbionts as a step toward the evolution of mitochondria.

Proceedings of the National Academy of Sciences of the United States of America pii:1813143115 [Epub ahead of print].

It has been hypothesized that mitochondria evolved from a bacterial ancestor that initially became established in an archaeal host cell as an endosymbiont. Here we model this first stage of mitochondrial evolution by engineering endosymbiosis between Escherichia coli and Saccharomyces cerevisiae An ADP/ATP translocase-expressing E. coli provided ATP to a respiration-deficient cox2 yeast mutant and enabled growth of a yeast-E. coli chimera on a nonfermentable carbon source. In a reciprocal fashion, yeast provided thiamin to an endosymbiotic E. coli thiamin auxotroph. Expression of several SNARE-like proteins in E. coli was also required, likely to block lysosomal degradation of intracellular bacteria. This chimeric system was stable for more than 40 doublings, and GFP-expressing E. coli endosymbionts could be observed in the yeast by fluorescence microscopy and X-ray tomography. This readily manipulated system should allow experimental delineation of host-endosymbiont adaptations that occurred during evolution of the current, highly reduced mitochondrial genome.

RevDate: 2018-10-30
CmpDate: 2018-10-30

Liu W, Hu C, Xie W, et al (2018)

The mitochondrial genome of red-necked phalarope Phalaropus lobatus (Charadriiformes: Scolopacidae) and phylogeny analysis among Scolopacidae.

Genes & genomics, 40(5):455-463.

The red-necked phalarope is a wonderful species with specific morphological characters and lifestyles. Mitochondrial genomes, encoding necessary proteins involved in the system of energy metabolism, are important for the evolution and adaption of species. In this study, we determined the complete mitogenome sequence of Phalaropus lobatus (Charadriiformes: Scolopacidae). The circular genome is 16714 bp in size, containing 13 PCGs, two ribosomal RNAs and 22 tRNAs and a high AT-rich control region. The AT skew and GC skew of major strand is positive and negative respectively. Most of PCGs are biased towards A-rich except ND1. A codon usage analysis shows that 3 start codons (ATG, GTG and ATA), 4 stop codons (TAA, TAG, AGG, AGA) and two incomplete terminate codons (T-). Twenty two transfer RNAs have the typical cloverleaf structure, and a total of ten base pairs are mismatched throughout the nine tRNA genes. The phylogenetic tree based on 13 PCGs and 2 rRNA genes indicates that monophyly of the family and genus Phalaropus is close to genus Xenus plus Tringa. The analysis of selective pressure shows 13 protein-coding genes are evolving under the purifying selection and P. lobatus is different from other Scolopacidae species on the selective pressure of gene ND4. This study helps us know the inherent mechanism of mitochondrial structure and natural selection.

RevDate: 2018-10-30
CmpDate: 2018-10-30

Guillory WX, Onyshchenko A, Ruck EC, et al (2018)

Recurrent Loss, Horizontal Transfer, and the Obscure Origins of Mitochondrial Introns in Diatoms (Bacillariophyta).

Genome biology and evolution, 10(6):1504-1515.

We sequenced mitochondrial genomes from five diverse diatoms (Toxarium undulatum, Psammoneis japonica, Eunotia naegelii, Cylindrotheca closterium, and Nitzschia sp.), chosen to fill important phylogenetic gaps and help us characterize broadscale patterns of mitochondrial genome evolution in diatoms. Although gene content was strongly conserved, intron content varied widely across species. The vast majority of introns were of group II type and were located in the cox1 or rnl genes. Although recurrent intron loss appears to be the principal underlying cause of the sporadic distributions of mitochondrial introns across diatoms, phylogenetic analyses showed that intron distributions superficially consistent with a recurrent-loss model were sometimes more complicated, implicating horizontal transfer as a likely mechanism of intron acquisition as well. It was not clear, however, whether diatoms were the donors or recipients of horizontally transferred introns, highlighting a general challenge in resolving the evolutionary histories of many diatom mitochondrial introns. Although some of these histories may become clearer as more genomes are sampled, high rates of intron loss suggest that the origins of many diatom mitochondrial introns are likely to remain unclear.

RevDate: 2018-10-29
CmpDate: 2018-10-29

Luévano-Martínez LA, AJ Kowaltowski (2017)

Topological characterization of the mitochondrial phospholipid scramblase 3.

FEBS letters, 591(24):4056-4066.

Scramblases redistribute phospholipids in biological membranes. Phospholipid scramblase 3 (PLSCR3), which is located in mitochondria, has been reported to be involved in cardiolipin distribution from the inner to the outer membrane, thus regulating cellular processes such as apoptosis or mitophagy. However, the localization and topology of this protein has not been convincingly addressed to support a role in intermembrane phospholipid transfer. Here, we studied PLSCR3 topology within mitochondria. We show that PLSCR3 inserts in the inner membrane (IM) via its C-terminal transmembrane helix, whereas its N-terminal portion is oriented toward the intermembrane space where it is activated by calcium. Our results suggest that PLSCR3, via its C-terminal transmembrane domain, participates in the bidirectional movement of phospholipids within the IM.

RevDate: 2018-10-29
CmpDate: 2018-10-29

Wang Q, Zhang C, Wang C, et al (2017)

Further characterization of Maize chlorotic mottle virus and its synergistic interaction with Sugarcane mosaic virus in maize.

Scientific reports, 7:39960 pii:srep39960.

Maize chlorotic mottle virus (MCMV) was first reported in maize in China in 2009. In this study we further analyzed the epidemiology of MCMV and corn lethal necrosis disease (CLND) in China. We determined that CLND observed in China was caused by co-infection of MCMV and sugarcane mosaic virus (SCMV). Phylogenetic analysis using four full-length MCMV cDNA sequences obtained in this study and the available MCMV sequences retrieved from GenBank indicated that Chinese MCMV isolates were derived from the same source. To screen for maize germplasm resistance against MCMV infection, we constructed an infectious clone of MCMV isolate YN2 (pMCMV) and developed an Agrobacterium-mediated injection procedure to allow high throughput inoculations of maize with the MCMV infectious clone. Electron microscopy showed that chloroplast photosynthesis in leaves was significantly impeded by the co-infection of MCMV and SCMV. Mitochondria in the MCMV and SCMV co-infected cells were more severely damaged than in MCMV-infected cells. The results of this study provide further insight into the epidemiology of MCMV in China and shed new light on physiological and cytopathological changes related to CLND in maize.

RevDate: 2018-10-28

Olsson M, Friesen CR, Rollings N, et al (2018)

Long term effects of superoxide and DNA repair on lizard telomeres.

Molecular ecology [Epub ahead of print].

Telomeres are the non-coding protein-nucleotide 'caps' at chromosome ends that contribute to chromosomal stability by protecting the coding parts of the linear DNA from shortening at cell division, and from erosion by reactive molecules. Recently, there has been some controversy between molecular and cell biologists, on the one hand, and evolutionary ecologists on the other, regarding whether reactive molecules erode telomeres during oxidative stress. Many studies of biochemistry and medicine have verified these relationships in cell culture, but other researchers have failed to find such effects in free-living vertebrates. Here we use a novel approach to measure free radicals (superoxide), mitochondrial 'content' (a combined measure of mitochondrial number and size in cells), telomere length and DNA damage at two primary time points during the mating season of an annual lizard species (Ctenophorus pictus). Superoxide levels early in the mating season vary widely and elevated levels predict shorter telomeres both at that time as well as several months later. These effects are likely driven by mitochondrial content, which significantly impacts late season superoxide (cells with more mitochondria have more superoxide), but superoxide effects on telomeres are counteracted by DNA repair as revealed by 8-hydroxy-2'-deoxyguanosine assays. We conclude that reactive oxygen species and DNA repair are fundamental for both short- and long-term regulation of lizard telomere length with pronounced effects of early-season cellular stress detectable on telomere length near lizard death. This article is protected by copyright. All rights reserved.

RevDate: 2018-10-25

Yu J, Zhang L, Li Y, et al (2018)

The Adrenal Lipid Droplet is a New Site for Steroid Hormone Metabolism.

Proteomics [Epub ahead of print].

Steroid hormones play essential roles for living organisms. It has been long and well established that the endoplasmic reticulum (ER) and mitochondria are essential sites for steroid hormone biosynthesis because several steroidogenic enzymes are located in these organelles. The adrenal gland lipid droplet (LD) proteomes from human, macaque monkey, and rodent were analyzed, revealing that steroidogenic enzymes are also present in abundance on LDs. The enzymes found include 3β-hydroxysteroid dehydrogenase (HSD3B), and estradiol 17β-dehydrogenase 11 (HSD17B11). Analyses by Western blot and subcellular localization consistently demonstrated that HSD3B2 was localized on LDs. Furthermore, in vitro experiments confirmed that the isolated LDs from HeLa cell stably expressing HSD3B2 or from rat adrenal glands had the capacity to convert pregnenolone to progesterone. Collectively, these data suggest that LDs may be important sites of steroid hormone metabolism. These findings may bring novel insights into the biosynthesis and metabolism of steroid hormones and the development of treatments for adrenal disorders. This article is protected by copyright. All rights reserved.

RevDate: 2018-10-25

Paris Z, JD Alfonzo (2018)

How the intracellular partitioning of tRNA and tRNA modification enzymes affects mitochondrial function.

IUBMB life [Epub ahead of print].

Organisms have evolved different strategies to seclude certain molecules to specific locations of the cell. This is most pronounced in eukaryotes with their extensive intracellular membrane systems. Intracellular compartmentalization is particularly critical in genome containing organelles, which because of their bacterial evolutionary ancestry still maintain protein-synthesis machinery that resembles more their evolutionary origin than the extant eukaryotic cell they once joined as an endosymbiont. Despite this, it is clear that genome-containing organelles such as the mitochondria are not in isolation and many molecules make it across the mitochondrial membranes from the cytoplasm. In this realm the import of tRNAs and the enzymes that modify them prove most consequential. In this review, we discuss two recent examples of how modifications typically found in cytoplasmic tRNAs affect mitochondrial translation in organisms that forcibly import all their tRNAs from the cytoplasm. In our view, the combination of tRNA import and the compartmentalization of modification enzymes must have played a critical role in the evolution of the organelle. © 2018 IUBMB Life, 2018.

RevDate: 2018-10-25

Gabaldón T (2018)

Relative timing of mitochondrial endosymbiosis and the "pre-mitochondrial symbioses" hypothesis.

IUBMB life [Epub ahead of print].

The origin of eukaryotes stands as a major open question in biology. Central to this question is the nature and timing of the origin of the mitochondrion, an ubiquitous eukaryotic organelle originated by the endosymbiosis of an alphaproteobacterial ancestor. Different hypotheses disagree, among other aspects, on whether mitochondria were acquired early or late during eukaryogenesis. Similarly, the nature and complexity of the receiving host is debated, with models ranging from a simple prokaryotic host to an already complex proto-eukaryote. Here, I will discuss recent findings from phylogenomics analyses of extant genomes that are shedding light into the evolutionary origins of the eukaryotic ancestor, and which suggest a later acquisition of alpha-proteobacterial derived proteins as compared to those with different bacterial ancestries. I argue that simple eukaryogenesis models that assume a binary symbiosis between an archaeon host and an alpha-proteobacterial proto-mitochondrion cannot explain the complex chimeric nature that is inferred for the eukaryotic ancestor. To reconcile existing hypotheses with the new data, I propose the "pre-mitochondrial symbioses" hypothesis that provides a framework for eukaryogenesis scenarios involving alternative symbiotic interactions that predate the acquisition of mitochondria. © 2018 IUBMB Life, 2018.

RevDate: 2018-10-22

Ligas J, Pineau E, Bock R, et al (2018)

The assembly pathway of Complex I in Arabidopsis thaliana.

The Plant journal : for cell and molecular biology [Epub ahead of print].

All present-day mitochondria originate from a single endosymbiotic event that gave rise to the last eukaryotic common ancestor (LECA) more than a billion years ago. However, to date, many aspects of mitochondrial evolution have remained unresolved. Comparative genomics and proteomics have revealed a complex evolutionary origin of many mitochondrial components. To understand the evolution of the respiratory chain, we have examined both the components and the mechanisms of the assembly pathway of complex I. Complex I represents the first enzyme of the respiratory chain, and complex I deficiencies have dramatic consequences in both animals and plants. The complex is located in the mitochondrial inner membrane and possesses two arms: one embedded in the inner membrane and one protruding in the matrix. Here, we describe the assembly pathway of complex I in the model plant Arabidopsis thaliana. Using a proteomic approach called complexome profiling, we have resolved the different steps in the assembly process in plants. We are proposing a model for the stepwise assembly of complex I including every subunit. We then compared this pathway with the corresponding pathway in humans and found that complex I assembly in plants follows a different, and likely ancestral, pathway compared to the one in humans. We show that the main evolutionary changes in complex I structure and assembly in humans occurred at the level of the membrane arm, whereas the matrix arm remained rather conserved. This article is protected by copyright. All rights reserved.

RevDate: 2018-10-20

Arakawa T, Ue S, Sano C, et al (2018)

Identification and characterization of a semi-dominant restorer-of-fertility 1 allele in sugar beet (Beta vulgaris).

TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik pii:10.1007/s00122-018-3211-6 [Epub ahead of print].

KEY MESSAGE: The sugar beet Rf1 locus has a number of molecular variants. We found that one of the molecular variants is a weak allele of a previously identified allele. Male sterility (MS) caused by nuclear-mitochondrial interaction is called cytoplasmic male sterility (CMS) in which MS-inducing mitochondria are suppressed by a nuclear gene, restorer-of-fertility. Rf and rf are the suppressing and non-suppressing alleles, respectively. This dichotomic view, however, seems somewhat unsatisfactory to explain the recently discovered molecular diversity of Rf loci. In the present study, we first identified sugar beet line NK-305 as a new source of Rf1. Our crossing experiment revealed that NK-305 Rf1 is likely a semi-dominant allele that restores partial fertility when heterozygous but full fertility when homozygous, whereas Rf1 from another sugar beet line appeared to be a dominant allele. Proper degeneration of anther tapetum is a prerequisite for pollen development; thus, we compared tapetal degeneration in the NK-305 Rf1 heterozygote and the homozygote. Degeneration occurred in both genotypes but to a lesser extent in the heterozygote, suggesting an association between NK-305 Rf1 dose and incompleteness of tapetal degeneration leading to partial fertility. Our protein analyses revealed a quantitative correlation between NK-305 Rf1 dose and a reduction in the accumulation of a 250 kDa mitochondrial protein complex consisting of a CMS-specific mitochondrial protein encoded by MS-inducing mitochondria. The abundance of Rf1 transcripts correlated with NK-305 Rf1 dose. The molecular organization of NK-305 Rf1 suggested that this allele evolved through intergenic recombination. We propose that the sugar beet Rf1 locus has a series of multiple alleles that differ in their ability to restore fertility and are reflective of the complexity of Rf evolution.

RevDate: 2018-10-21

Lou E, Zhai E, Sarkari A, et al (2018)

Cellular and Molecular Networking Within the Ecosystem of Cancer Cell Communication via Tunneling Nanotubes.

Frontiers in cell and developmental biology, 6:95.

Intercellular communication is vital to the ecosystem of cancer cell organization and invasion. Identification of key cellular cargo and their varied modes of transport are important considerations in understanding the basic mechanisms of cancer cell growth. Gap junctions, exosomes, and apoptotic bodies play key roles as physical modalities in mediating intercellular transport. Tunneling nanotubes (TNTs)-narrow actin-based cytoplasmic extensions-are unique structures that facilitate direct, long distance cell-to-cell transport of cargo, including microRNAs, mitochondria, and a variety of other sub cellular components. The transport of cargo via TNTs occurs between malignant and stromal cells and can lead to changes in gene regulation that propagate the cancer phenotype. More notably, the transfer of these varied molecules almost invariably plays a critical role in the communication between cancer cells themselves in an effort to resist death by chemotherapy and promote the growth and metastases of the primary oncogenic cell. The more traditional definition of "Systems Biology" is the computational and mathematical modeling of complex biological systems. The concept, however, is now used more widely in biology for a variety of contexts, including interdisciplinary fields of study that focus on complex interactions within biological systems and how these interactions give rise to the function and behavior of such systems. In fact, it is imperative to understand and reconstruct components in their native context rather than examining them separately. The long-term objective of evaluating cancer ecosystems in their proper context is to better diagnose, classify, and more accurately predict the outcome of cancer treatment. Communication is essential for the advancement and evolution of the tumor ecosystem. This interplay results in cancer progression. As key mediators of intercellular communication within the tumor ecosystem, TNTs are the central topic of this article.

RevDate: 2018-10-24

Zhu Y, Gu X, C Xu (2018)

Mitochondrial DNA 7908-8816 region mutations in maternally inherited essential hypertensive subjects in China.

BMC medical genomics, 11(1):89 pii:10.1186/s12920-018-0408-0.

BACKGROUND: Nuclear genes or family-based mitochondrial screening have been the focus of genetic studies into essential hypertension. Studies into the role of mitochondria in sporadic Chinese hypertensives are lacking. The objective of the study was to explore the relationship between mitochondrial DNA (mtDNA) variations and the development of maternally inherited essential hypertension (MIEH) in China.

METHODS: Yangzhou residents who were outpatients or in-patients at the Department of Cardiology in Northern Jiangsu People's Hospital (Jiangsu, China) from June 2009 to June 2015 were recruited in a 1:1 case control study of 600 gender-matched Chinese MIEH subjects and controls. Genomic DNA was isolated from whole blood cells. The most likely sites for hypertension were screened using oligodeoxynucleotides at positions 7908-8816, purified and subsequently analyzed by direct sequencing according to the revised consensus Cambridge sequence. The frequency, density, type and conservative evolution of mtDNA variations were comprehensively analyzed.

RESULTS: We found a statistical difference between the two groups for body mass index, waist circumference, abdominal circumference, triglyceride, low-density lipoprotein cholesterol, fasting blood glucose, uric acid, creatinine and blood urea nitrogen (P < 0.05). More amino-acid changes and RNA variants were found in MIEH subjects than the controls (P < 0.01). The detection system simultaneously identified 40 different heteroplasmic or homoplasmic mutations in 4 genes: COXII, tRNALys, ATP8 and ATP 6. The mtDNA variations were mainly distributed in regions of ATP6 binding sites, and the site of highest mutation frequency was m. 8414C > T. Three changes in single bases (C8414T in ATP8, A8701G in ATP6 and G8584A in ATP6) were significantly different in the MIEH patients and the controls (P < 0.001). The m.8273_8281del mutation was identified from 59 MIEH patients.

CONCLUSIONS: Our results indicate that novel mtDNA mutations may be involved in the pathological process of MIEH, and mitochondrial genetic characteristics were identified in MIEH individuals.

RevDate: 2018-10-10

Burger G, M Valach (2018)

Perfection of eccentricity: Mitochondrial genomes of diplonemids.

IUBMB life [Epub ahead of print].

Mitochondria are the sandbox of evolution as exemplified most particularly by the diplonemids, a group of marine microeukaryotes. These protists are uniquely characterized by their highly multipartite mitochondrial genome and systematically fragmented genes whose pieces are spread out over several dozens of chromosomes. The type species Diplonema papillatum was the first member of this group in which the expression of fragmented mitochondrial genes was investigated experimentally. We now know that gene expression involves separate transcription of gene pieces (modules), RNA editing of module transcripts, and module joining to mature mRNAs and rRNAs. The mechanism of cognate module recognition and ligation is distinct from known intron splicing and remains to be uncovered. Here, we review the current status of research on mitochondrial genome architecture, as well as gene complement, structure, and expression modes in diplonemids. Further, we discuss the potential molecular mechanisms of posttranscriptional processing, and finally reflect on the evolutionary trajectories and trends of mtDNA evolution as seen in this protist group. © 2018 IUBMB Life, 2018.

RevDate: 2018-10-10

Urantowka AD, Kroczak A, Silva T, et al (2018)

New insight into parrots' mitogenomes indicates that their ancestor contained a duplicated region.

Molecular biology and evolution pii:5126238 [Epub ahead of print].

Mitochondrial genomes of vertebrates are generally thought to evolve under strong selection for size reduction and gene order conservation. Therefore, a growing number of mitogenomes with duplicated regions changes our view on the genome evolution. Among Aves, order Psittaciformes (parrots) is especially noteworthy because of its large morphological, ecological and taxonomical diversity, which offers an opportunity to study genome evolution in various aspects. Former analyses showed that tandem duplications comprising the control region with adjacent genes are restricted to several lineages in which the duplication occurred independently. However, using an appropriate PCR strategy, we demonstrate that early diverged parrot groups contain mitogenomes with the duplicated region. These findings together with mapping duplication data from other mitogenomes onto parrot phylogeny indicate that the duplication was an ancestral state for Psittaciformes. The state was inherited by main parrot groups and was lost several times in some lineages. The duplicated regions were subjected to concerted evolution with a frequency higher than the rate of speciation. The duplicated control regions may provide a selective advantage due to a more efficient initiation of replication or transcription and a larger number of replicating genomes per organelle, which may lead to a more effective energy production by mitochondria. The mitogenomic duplications were associated with phenotypic features and parrots with the duplicated region can live longer, show larger body mass as well as predispositions to a more active flight. The results have wider implications on the presence of duplications and their evolution in mitogenomes of other avian groups.

RevDate: 2018-10-03

van Esveld SL, MA Huynen (2018)

Does mitochondrial DNA evolution in metazoa drive the origin of new mitochondrial proteins?.

IUBMB life [Epub ahead of print].

Most eukaryotic cells contain mitochondria with a genome that evolved from their α-proteobacterial ancestor. In the course of eukaryotic evolution, the mitochondrial genome underwent a dramatic reduction in size, caused by the loss and translocation of genes. This required adjustments in mitochondrial gene expression mechanisms and resulted in a complex collaborative system of mitochondrially encoded transfer RNAs and ribosomal RNAs with nuclear encoded proteins to express the mitochondrial encoded oxidative phosphorylation (OXPHOS) proteins. In this review, we examine mitochondrial gene expression from an evolutionary point of view: to what extent can we correlate changes in the mitochondrial genome in the evolutionary lineage leading to human with the origin of new nuclear encoded proteins. We dated the evolutionary origin of mitochondrial proteins that interact with mitochondrial DNA or its RNA and/or protein products in a systematic manner and compared them with documented changes in the mitochondrial DNA. We find anecdotal but accumulating evidence that metazoan RNA-interacting proteins arose in conjunction with changes of the mitochondrial DNA. We find no substantial evidence for such compensatory evolution in new OXPHOS proteins, which appear to be constrained by the ability to form supercomplexes. © 2018 IUBMB Life, 1-11, 2018.

RevDate: 2018-10-03

Harborne SPD, ERS Kunji (2018)

Calcium-regulated mitochondrial ATP-Mg/Pi carriers evolved from a fusion of an EF-hand regulatory domain with a mitochondrial ADP/ATP carrier-like domain.

IUBMB life [Epub ahead of print].

The mitochondrial ATP-Mg/Pi carrier is responsible for the calcium-dependent regulation of adenosine nucleotide concentrations in the mitochondrial matrix, which allows mitochondria to respond to changing energy requirements of the cell. The carrier is expressed in mitochondria of fungi, plants and animals and belongs to the family of mitochondrial carriers. The carrier is unusual as it consists of three separate domains: (i) an N-terminal regulatory domain with four calcium-binding EF-hands similar to calmodulin, (ii) a loop domain containing an amphipathic α-helix and (iii) a mitochondrial carrier domain related to the mitochondrial ADP/ATP carrier. This striking example of three domains coming together from different origins to provide new functions represents an interesting quirk of evolution. In this review, we outline how the carrier was identified and how its physiological role was established with a focus on human isoforms. We exploit the sequence and structural information of the domains to explore the similarities and differences to their closest counterparts; mitochondrial ADP/ATP carriers and proteins with four EF-hands. We discuss how their combined function has led to a mechanism for calcium-regulated transport of adenosine nucleotides. Finally, we compare the ATP-Mg/Pi carrier with the mitochondrial aspartate/glutamate carrier, the only other mitochondrial carrier regulated by calcium, and we will argue that they have arisen by convergent rather than divergent evolution. © 2018 The Authors IUBMB Life published by Wiley Periodicals, Inc. on behalf of International Union of Biochemistry and Molecular Biology, 2018.

RevDate: 2018-10-23

Pereira J, AN Lupas (2018)

The Origin of Mitochondria-Specific Outer Membrane β-Barrels from an Ancestral Bacterial Fragment.

Genome biology and evolution, 10(10):2759-2765 pii:5110071.

Outer membrane β-barrels (OMBBs) are toroidal arrays of antiparallel β-strands that span the outer membrane of Gram-negative bacteria and eukaryotic organelles. Although homologous, most families of bacterial OMBBs evolved through the independent amplification of an ancestral ββ-hairpin. In mitochondria, one family (SAM50) has a clear bacterial ancestry; the origin of the other family, consisting of 19-stranded OMBBs found only in mitochondria (MOMBBs), is substantially unclear. In a large-scale comparison of mitochondrial and bacterial OMBBs, we find evidence that the common ancestor of all MOMBBs emerged by the amplification of a double ββ-hairpin of bacterial origin, probably at the time of the Last Eukaryotic Common Ancestor. Thus, MOMBBs are indeed descended from bacterial OMBBs, but their fold formed independently in the proto-mitochondria, possibly in response to the need for a general-purpose polypeptide importer. This occurred by a process of amplification, despite the final fold having a prime number of strands.

RevDate: 2018-10-02

Huang Y, Zheng S, Mei X, et al (2018)

A secretory hexokinase plays an active role in the proliferation of Nosema bombycis.

PeerJ, 6:e5658 pii:5658.

The microsporidian Nosema bombycis is an obligate intracellular parasite of Bombyx mori, that lost its intact tricarboxylic acid cycle and mitochondria during evolution but retained its intact glycolysis pathway. N. bombycis hexokinase (NbHK) is not only a rate-limiting enzyme of glycolysis but also a secretory protein. Indirect immunofluorescence assays and recombinant HK overexpressed in BmN cells showed that NbHK localized in the nucleus and cytoplasm of host cell during the meront stage. When N. bombycis matured, NbHK tended to concentrate at the nuclei of host cells. Furthermore, the transcriptional profile of NbHK implied it functioned during N. bombycis' proliferation stages. A knock-down of NbHK effectively suppressed the proliferation of N. bombycis indicating that NbHK is an important protein for parasite to control its host.

RevDate: 2018-09-26

McClelland GB, GR Scott (2018)

Evolved Mechanisms of Aerobic Performance and Hypoxia Resistance in High-Altitude Natives.

Annual review of physiology [Epub ahead of print].

Comparative physiology studies of high-altitude species provide an exceptional opportunity to understand naturally evolved mechanisms of hypoxia resistance. Aerobic capacity (VO2max) is a critical performance trait under positive selection in some high-altitude taxa, and several high-altitude natives have evolved to resist the depressive effects of hypoxia on VO2max. This is associated with enhanced flux capacity through the O2 transport cascade and attenuation of the maladaptive responses to chronic hypoxia that can impair O2 transport. Some highlanders exhibit elevated rates of carbohydrate oxidation during exercise, taking advantage of its high ATP yield per mole of O2. Certain highland native animals have also evolved more oxidative muscles and can sustain high rates of lipid oxidation to support thermogenesis. The underlying mechanisms include regulatory adjustments of metabolic pathways and to gene expression networks. Therefore, the evolution of hypoxia resistance in high-altitude natives involves integrated functional changes in the pathways for O2 and substrate delivery and utilization by mitochondria. Expected final online publication date for the Annual Review of Physiology Volume 81 is February 10, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

RevDate: 2018-09-13

Geary DC (2018)

Efficiency of mitochondrial functioning as the fundamental biological mechanism of general intelligence (g).

Psychological review pii:2018-44565-001 [Epub ahead of print].

General intelligence or g is one of the most thoroughly studied concepts in the behavioral sciences. Measures of intelligence are predictive of a wide range of educational, occupational, and life outcomes, including creative productivity and are systematically related to physical health and successful aging. The nexus of relations suggests 1 or several fundamental biological mechanisms underlie g, health, and aging, among other outcomes. Cell-damaging oxidative stress has been proposed as 1 of many potential mechanisms, but the proposal is underdeveloped and does not capture other important mitochondrial functions. I flesh out this proposal and argue that the overall efficiency of mitochondrial functioning is a core component of g; the most fundamental biological mechanism common to all brain and cognitive processes and that contributes to the relations among intelligence, health, and aging. The proposal integrates research on intelligence with models of the centrality of mitochondria to brain development and functioning, neurological diseases, and health more generally. Moreover, the combination of the maternal inheritance of mitochondrial DNA (mtDNA), the evolution of compensatory nuclear DNA, and the inability of evolutionary processes to purge deleterious mtDNA in males may contribute to the sex difference in variability in intelligence and in other cognitive domains. The proposal unifies many now disparate literatures and generates testable predictions for future studies. (PsycINFO Database Record

RevDate: 2018-09-13

Sandor S, Zhang Y, J Xu (2018)

Fungal mitochondrial genomes and genetic polymorphisms.

Applied microbiology and biotechnology pii:10.1007/s00253-018-9350-5 [Epub ahead of print].

Mitochondria are the powerhouses of eukaryotic cells, responsible for ATP generation and playing a role in a diversity of cellular and organismal functions. Different from the majority of other intracellular membrane structures, mitochondria contain their own genetic materials that are capable of independent replication and inheritance. In this mini-review, we provide brief summaries of fungal mitochondrial genome structure, size, gene content, inheritance, and genetic variation. We pay special attention to the relative genetic polymorphisms of the mitochondrial vs nuclear genomes at the population level within individual fungal species. Among the 20 species/groups of species reviewed here, there is a range of variation among genes and species in the relative nuclear and mitochondrial genetic polymorphisms. Interestingly, most (15/20) showed a greater genetic diversity for nuclear genes and genomes than for mitochondrial genes and genomes, with the remaining five showing similar or slower nuclear genome genetic variations. This fungal pattern is different from the dominant pattern in animals, but more similar to that in plants. At present, the mechanisms for the variations among fungal species and the overall low level of mitochondrial sequence polymorphisms are not known. The increasing availability of population genomic data should help us reveal the potential genetic and ecological factors responsible for the observed variations.

RevDate: 2018-09-16

Jebb D, Foley NM, Whelan CV, et al (2018)

Population level mitogenomics of long-lived bats reveals dynamic heteroplasmy and challenges the Free Radical Theory of Ageing.

Scientific reports, 8(1):13634 pii:10.1038/s41598-018-31093-2.

Bats are the only mammals capable of true, powered flight, which drives an extremely high metabolic rate. The "Free Radical Theory of Ageing" (FTRA) posits that a high metabolic rate causes mitochondrial heteroplasmy and the progressive ageing phenotype. Contrary to this, bats are the longest-lived order of mammals given their small size and high metabolic rate. To investigate if bats exhibit increased mitochondrial heteroplasmy with age, we performed targeted, deep sequencing of mitogenomes and measured point heteroplasmy in wild, long lived Myotis myotis. Blood was sampled from 195 individuals, aged between <1 and at 6+ years old, and whole mitochondria deep-sequenced, with a subset sampled over multiple years. The majority of heteroplasmies were at a low frequency and were transitions. Oxidative mutations were present in only a small number of individuals, suggesting local oxidative stress events. Cohort data showed no significant increase in heteroplasmy with age, while longitudinal data from recaptured individuals showed heteroplasmy is dynamic, and does not increase uniformly over time. We show that bats do not suffer from the predicted, inevitable increase in heteroplasmy as posited by the FRTA, instead heteroplasmy was found to be dynamic, questioning its presumed role as a primary driver of ageing.

RevDate: 2018-10-19
CmpDate: 2018-10-19

Eom KS, Park H, Lee D, et al (2018)

Molecular and Morphologic Identification of Spirometra ranarum Found in the Stool of African Lion, Panthera leo in the Serengeti Plain of Tanzania.

The Korean journal of parasitology, 56(4):379-383.

The present study was performed with morphological and molecular analysis (cox1 and nad1 mitochondrial genes) to identify the proglottids of spirometrid tapeworm found in the stool of an African lion, Panthera leo, in the Serengeti plain of Tanzania. A strand of tapeworm strobila, about 75 cm in length, was obtained in the stool of a male African lion in the Serengeti National Park (34˚ 50' E, 02˚ 30' S), Tanzania, in February 2012. The morphological features of the adult worm examined exhibited 3 uterine coils with a bow tie appearance and adopted a diagonal direction in the second turn. The posterior uterine coils are larger than terminal uterine ball and the feature of uteri are swirling rather than spirally coiling. The sequence difference between the Spirometra species (Tanzania origin) and S. erinaceieuropaei (GenBank no. KJ599680) was 9.4% while those of S. decipiens (GenBank no. KJ599679) differed by 2.1% in the cox1 and nad1 genes. Phylogenetic tree topologies generated using the 2 analytic methods were identical and presented high level of confidence values for the 3 major branches of the 3 Spirometra species in the cox1 gene. The morphological and molecular findings obtained in this study were nearly coincided with those of S. ranarum. Therefore, we can know for the first time that the African lion, Panthera leo, is to the definitive host of this tapeworm.

RevDate: 2018-09-14
CmpDate: 2018-09-14

Verechshagina NA, Konstantinov YM, Kamenski PA, et al (2018)

Import of Proteins and Nucleic Acids into Mitochondria.

Biochemistry. Biokhimiia, 83(6):643-661.

Many mitochondrial genes have been transferred to the nucleus in course of evolution. The products of expression of these genes, being still necessary for organelle function, are imported there from the cytosol. Molecular mechanisms of protein import are studied much deeper than those of nucleic acids. The latter, it seems to us, retards the development of mitochondrial genome editing technologies. In this review, we describe mechanisms of DNA, RNA, and protein import into mitochondria of different eukaryotes. The description is given for the natural processes, as well as for artificial targeting of macromolecules into mitochondria for therapy. Also, we discuss different approaches to introduce changes into the mitochondrial DNA sequence.

RevDate: 2018-09-04

Haenel GJ, V Del Gaizo Moore (2018)

Functional Divergence of Mitochondria and Coevolution of Genomes: Cool Mitochondria in Hot Lizards.

Physiological and biochemical zoology : PBZ, 91(5):1068-1081.

Mitochondria play a key role in the ecology and evolution of species through their influence on aerobic metabolism. Mitochondrial DNA (mtDNA) and nuclear genomes must interact for optimal functioning of oxidative phosphorylation to produce ATP, and breakdown of coadaptation components from each may have important evolutionary consequences for hybridization. Introgression of mitochondria in natural populations through hybridization with unidirectional backcrossing allows the testing of coadaptation of mitochondria to different nuclear backgrounds. We compared the function of mitochondria isolated from two species of Urosaurus lizards and hybrid populations. Due to past introgression, hybrids contain the nuclear genome of the "hot-adapted" species (U. graciosus) but the mtDNA of the less heat-tolerant species (U. ornatus). It was found that the function of the parental forms of mitochondria had significantly diverged with the hot-adapted species. There was significant genotype × genotype × environment interactions for mitochondrial membrane potential and genotype × genotype interactions for ATP production. Membrane potential decreased less at a higher temperature, while ATP production was higher at both temperatures in introgressed mitochondria. Oxygen consumption was lower in U. graciosus than in U. ornatus parental-type mitochondria, indicating a likely response to living in hotter environments. Respiratory control ratio values, which provide an indication of the functional quality of isolated mitochondria, were lower in introgressed mitochondria than in parental U. ornatus types, indicating a negative impact on biological function in introgressed mitochondria.

RevDate: 2018-10-15
CmpDate: 2018-10-15

Matthee CA, Engelbrecht A, S Matthee (2018)

Comparative phylogeography of parasitic Laelaps mites contribute new insights into the specialist-generalist variation hypothesis (SGVH).

BMC evolutionary biology, 18(1):131 pii:10.1186/s12862-018-1245-7.

BACKGROUND: The specialist-generalist variation hypothesis (SGVH) in parasites suggests that, due to patchiness in habitat (host availability), specialist species will show more subdivided population structure when compared to generalist species. In addition, since specialist species are more prone to local stochastic extinction events with their hosts, they will show lower levels of intraspecific genetic diversity when compared to more generalist.

RESULTS: To test the wider applicability of the SGVH we compared 337 cytochrome oxidase I mitochondrial DNA and 268 nuclear tropomyosin DNA sequenced fragments derived from two co-distributed Laelaps mite species and compared the data to 294 COI mtDNA sequences derived from the respective hosts Rhabdomys dilectus, R. bechuanae, Mastomys coucha and M. natalensis. In support of the SGVH, the generalist L. muricola was characterized by a high mtDNA haplotypic diversity of 0.97 (±0.00) and a low level of population differentiation (mtDNA Fst = 0.56, p < 0.05; nuDNA Fst = 0.33, P < 0.05) while the specialist L. giganteus was overall characterized by a lower haplotypic diversity of 0.77 (±0.03) and comparatively higher levels of population differentiation (mtDNA Fst = 0.87, P < 0.05; nuDNA Fst = 0.48, P < 0.05). When the two specialist L. giganteus lineages, which occur on two different Rhabdomys species, are respectively compared to the generalist parasite, L. muricola, the SGVH is not fully supported. One of the specialist L. giganteus species occurring on R. dilectus shows similar low levels of population differentiation (mtDNA Fst = 0.53, P < 0.05; nuDNA Fst = 0.12, P < 0.05) than that found for the generalist L. muricola. This finding can be correlated to differences in host dispersal: R. bechuanae populations are characterized by a differentiated mtDNA Fst of 0.79 (P < 0.05) while R. dilectus populations are less structured with a mtDNA Fst = 0.18 (P < 0.05).

CONCLUSIONS: These findings suggest that in ectoparasites, host specificity and the vagility of the host are both important drivers for parasite dispersal. It is proposed that the SGHV hypothesis should also incorporate reference to host dispersal since in our case only the specialist species who occur on less mobile hosts showed more subdivided population structure when compared to generalist species.

RevDate: 2018-10-15
CmpDate: 2018-10-15

Yin M, Wang X, Ma X, et al (2018)

Cytonuclear diversity and shared mitochondrial haplotypes among Daphnia galeata populations separated by seven thousand kilometres.

BMC evolutionary biology, 18(1):130 pii:10.1186/s12862-018-1256-4.

BACKGROUND: The zooplanktonic cladocerans Daphnia, present in a wide range of water bodies, are an important component of freshwater ecosystems. In contrast to their high dispersal capacity through diapausing eggs carried by waterfowl, Daphnia often exhibit strong population genetic differentiation. Here, to test for common patterns in the population genetic structure of a widespread Holarctic species, D. galeata, we genotyped two sets of populations collected from geographically distant areas: across 13 lakes in Eastern China and 14 lakes in Central Europe. The majority of these populations were genotyped at two types of markers: a mitochondrial gene (for 12S rRNA) and 15 nuclear microsatellite loci.

RESULTS: Mitochondrial DNA demonstrated relatively shallow divergence within D. galeata, with distinct haplotype compositions in the two study regions but one widely distributed haplotype shared between several of the Chinese as well as European populations. At microsatellite markers, clear separation was observed at both large (between China and Europe) and small (within Europe) geographical scales, as demonstrated by Factorial Correspondence Analyses, Bayesian assignment and a clustering method based on genetic distances. Genetic diversity was comparable between the sets of Chinese and European D. galeata populations for both types of markers. Interestingly, we observed a significant association between genetic distance and geographical distance for D. galeata populations in China but not in Europe.

CONCLUSIONS: Our results indicate relatively recent spread of D. galeata across wide expanses of the Palaearctic, with one mtDNA lineage of D. galeata successfully establishing over large distances. Despite a clear differentiation of Chinese and European D. galeata at a nuclear level, the pattern of genetic variation is nevertheless similar between both regions. Overall, our findings provide insights into the genetic population structure of a cladoceran species with extremely wide geographical range.

RevDate: 2018-10-12

Virji AZ, Thekkiniath J, Ma W, et al (2018)

Insights into the evolution and drug susceptibility of Babesia duncani from the sequence of its mitochondrial and apicoplast genomes.

International journal for parasitology pii:S0020-7519(18)30170-X [Epub ahead of print].

Babesia microti and Babesia duncani are the main causative agents of human babesiosis in the United States. While significant knowledge about B. microti has been gained over the past few years, nothing is known about B. duncani biology, pathogenesis, mode of transmission or sensitivity to currently recommended therapies. Studies in immunocompetent wild type mice and hamsters have shown that unlike B. microti, infection with B. duncani results in severe pathology and ultimately death. The parasite factors involved in B. duncani virulence remain unknown. Here we report the first known completed sequence and annotation of the apicoplast and mitochondrial genomes of B. duncani. We found that the apicoplast genome of this parasite consists of a 34 kb monocistronic circular molecule encoding functions that are important for apicoplast gene transcription as well as translation and maturation of the organelle's proteins. The mitochondrial genome of B. duncani consists of a 5.9 kb monocistronic linear molecule with two inverted repeats of 48 bp at both ends. Using the conserved cytochrome b (Cytb) and cytochrome c oxidase subunit I (coxI) proteins encoded by the mitochondrial genome, phylogenetic analysis revealed that B. duncani defines a new lineage among apicomplexan parasites distinct from B. microti, Babesia bovis, Theileria spp. and Plasmodium spp. Annotation of the apicoplast and mitochondrial genomes of B. duncani identified targets for development of effective therapies. Our studies set the stage for evaluation of the efficacy of these drugs alone or in combination against B. duncani in culture as well as in animal models.

RevDate: 2018-10-08
CmpDate: 2018-10-08

Galen SC, Nunes R, Sweet PR, et al (2018)

Integrating coalescent species delimitation with analysis of host specificity reveals extensive cryptic diversity despite minimal mitochondrial divergence in the malaria parasite genus Leucocytozoon.

BMC evolutionary biology, 18(1):128 pii:10.1186/s12862-018-1242-x.

BACKGROUND: Coalescent methods that use multi-locus sequence data are powerful tools for identifying putatively reproductively isolated lineages, though this approach has rarely been used for the study of microbial groups that are likely to harbor many unrecognized species. Among microbial symbionts, integrating genetic species delimitation methods with trait data that could indicate reproductive isolation, such as host specificity data, has rarely been used despite its potential to inform species limits. Here we test the ability of an integrative approach combining genetic and host specificity data to delimit species within the avian malaria parasite genus Leucocytozoon in central Alaska.

RESULTS: We sequenced seven nuclear loci for 69 Leucocytozoon samples and used multiple species delimitation methods (GMYC and BPP models), tested for differences in host infection patterns among putative species based on 406 individual infections, and characterized parasite morphology. We found that cryptic morphology has masked a highly diverse Leucocytozoon assemblage, with most species delimitation methods recovering support for at least 21 separate species that occur sympatrically and have divergent host infection patterns. Reproductive isolation among putative species appears to have evolved despite low mtDNA divergence, and in one instance two Leucocytozoon cytb haplotypes that differed by a single base pair (~ 0.2% divergence) were supported as separate species. However, there was no consistent association between mtDNA divergence and species limits. Among cytb haplotypes that differed by one to three base pairs we observed idiosyncratic patterns of nuclear and ecological divergence, with cytb haplotype pairs found to be either conspecific, reproductively isolated with no divergence in host specificity, or reproductively isolated with divergent patterns of host specialization.

CONCLUSION: Integrating multi-locus genetic species delimitation methods and non-traditional ecological data types such as host specificity provide a novel view of the diversity of avian malaria parasites that has been missed previously using morphology and mtDNA barcodes. Species delimitation methods show that Leucocytozoon is highly species-rich in Alaska, and the genus is likely to harbor extraordinary species-level diversity worldwide. Integrating genetic and ecological data will be an important approach for understanding the diversity and evolutionary history of microbial symbionts moving forward.

RevDate: 2018-08-31

Berzabá-Evoli E, Zazueta C, Cruz Hernández JH, et al (2018)

Leptin Modifies the Rat Heart Performance Associated with Mitochondrial Dysfunction Independently of Its Prohypertrophic Effects.

International journal of endocrinology, 2018:6081415.

Background: Functional receptors for leptin were described on the surface of cardiomyocytes, and there was a prohypertrophic effect with high concentrations of the cytokine. Therefore, leptin could be a link between obesity and the prevalence of cardiovascular diseases. On the other hand, a deleterious effect of leptin on mitochondrial performance was described, which was also associated with the evolution of cardiac hypertrophy to heart failure. The goal of our study was to analyze the effect of the exposure of rat hearts to a high concentration of leptin on cardiac and mitochondrial function.

Methods: Rat hearts were perfused continuously with or without 3.1 nM leptin for 1, 2, 3, or 4 hours. Homogenates and mitochondria were prepared by centrifugation and analyzed for cardiac actin, STAT3, and pSTAT3 by Western blotting, as well as for mitochondrial oxidative phosphorylation, membrane potential, swelling, calcium transport, and content of oxidized lipids.

Results: In our results, leptin induced an increased rate-pressure product as a result of increased heart rate and contraction force, as well oxidative stress. In addition, mitochondrial dysfunction expressed as a loss of membrane potential, decreased ability for calcium transport and retention, faster swelling, and less respiratory control was observed.

Conclusions: Our results support the role of leptin as a deleterious factor for cardiac function and indicates that mitochondrial dysfunction could be a trigger for cardiac hypertrophy and failure.

RevDate: 2018-10-12

Pustylnikov S, Costabile F, Beghi S, et al (2018)

Targeting mitochondria in cancer: current concepts and immunotherapy approaches.

Translational research : the journal of laboratory and clinical medicine pii:S1931-5244(18)30114-2 [Epub ahead of print].

An essential advantage during eukaryotic cell evolution was the acquisition of a network of mitochondria as a source of energy for cell metabolism and contrary to conventional wisdom, functional mitochondria are essential for the cancer cell. Multiple aspects of mitochondrial biology beyond bioenergetics support transformation including mitochondrial biogenesis, fission and fusion dynamics, cell death susceptibility, oxidative stress regulation, metabolism, and signaling. In cancer, the metabolism of cells is reprogrammed for energy generation from oxidative phosphorylation to aerobic glycolysis and impacts cancer mitochondrial function. Furthermore cancer cells can also modulate energy metabolism within the cancer microenvironment including immune cells and induce "metabolic anergy" of antitumor immune response. Classical approaches targeting the mitochondria of cancer cells usually aim at inducing changing energy metabolism or directly affecting functions of mitochondrial antiapoptotic proteins but most of such approaches miss the required specificity of action and carry important side effects. Several types of cancers harbor somatic mitochondrial DNA mutations and specific immune response to mutated mitochondrial proteins has been observed. An attractive alternative way to target the mitochondria in cancer cells is the induction of an adaptive immune response against mutated mitochondrial proteins. Here, we review the cancer cell-intrinsic and cell-extrinsic mechanisms through which mitochondria influence all steps of oncogenesis, with a focus on the therapeutic potential of targeting mitochondrial DNA mutations or Tumor Associated Mitochondria Antigens using the immune system.

RevDate: 2018-08-24

Boratyński JS, PA Szafrańska (2018)

Does Basal Metabolism Set the Limit for Metabolic Downregulation during Torpor?.

Physiological and biochemical zoology : PBZ, 91(5):1057-1067.

The evolution of endothermic thermoregulation is rooted in the processes involving high metabolism, which allows the maintenance of high and stable body temperatures (Tb). In turn, selection for high endothermic metabolism correlates with increased size of metabolically active organs and thus with high basal metabolic rate (BMR). Endothermic animals are characterized by an MR several times that of similar-sized ectotherms. However, many small mammals are temporally heterothermic and are able to temporally decrease Tb and MR by entering daily torpor or hibernation. Both BMR and minimum MR during torpor (TMRmin) likely result from oxidative respiration in mitochondria of the same tissues. It should be expected that these two MRs are positively correlated, suggesting that the evolution of endothermy and higher BMR set the limit for the ability to reduce MR while entering torpor. Using published data for 96 mammal species, we tested the hypothesis that, among heterothermic mammals, the processes leading to the evolution of higher BMR limit the ability to downregulate metabolism during torpor. We found that body mass (mb)-adjusted BMR was positively correlated with mb- and Tb-adjusted TMRmin, in a phylogenetically corrected analysis. Phylogenetic path modeling indicated that the mechanisms underlying the evolutionary increase of BMR in endotherms most likely constrain their ability to reduce MR during torpor. Given that heterothermy is considered an ancestral state in mammals, these results suggest an increase in BMR during the evolution of endothermy in homeothermic animals, which leads to the loss of their ability to enter torpor.

RevDate: 2018-09-13

Liu J, Kim SY, Shin S, et al (2018)

Overexpression of TFF3 is involved in prostate carcinogenesis via blocking mitochondria-mediated apoptosis.

Experimental & molecular medicine, 50(8):110 pii:10.1038/s12276-018-0137-7.

The overexpression of trefoil factor family 3 (TFF3) is observed in a variety of cancers, including prostate cancer (PCa), and its potential role in carcinogenesis, such as activating the PI3K/AKT pathway, is suggested. However, its role and its related mechanisms in prostate tumorigenesis remain unknown. To elucidate the role of TFF3 overexpression in PCa, we silenced TFF3 in two PCa cell lines that overexpressed TFF3 and explored the molecular mechanism behind its antiapoptotic role. We also examined TFF3 expression in 108 Korean PCa specimens and 106 normal prostate tissues by immunohistochemistry (IHC) analysis. The mean TFF3 IHC score in the tumor tissues was significantly higher than that in the normal tissues (4.702 vs. 0.311, P = 2.52 × 10-24). TFF3-silenced cells showed suppressed tumor cell growth and migration. TFF3 silencing decreased BCL2 and increased BAX expression. The translocation of BAX to the mitochondria was also confirmed. After TFF3 silencing, the expression of the mitochondrial proapoptotic proteins, cytochrome C and Smac/DIABLO, was elevated, and these proteins were released from the mitochondria to the cytosol. Downstream mediators of mitochondrial apoptosis, including cleaved caspase-3, caspase-9, and PARP, were also elevated. Accordingly, the proportion of apoptotic cells was significantly higher among TFF3-silenced cells. There was no difference in extrinsic apoptosis-related molecules after TFF3 silencing. All the results support that TFF3 silencing induces the downstream signaling pathway of mitochondria-mediated apoptosis. This study provides a better understanding of the mechanism of prostate tumorigenesis, suggesting TFF3 as a potential biomarker and therapeutic target of PCa.

RevDate: 2018-10-20

Kagda MS, Vu AL, Ah-Fong AMV, et al (2018)

Phosphagen kinase function in flagellated spores of the oomycete Phytophthora infestans integrates transcriptional regulation, metabolic dynamics and protein retargeting.

Molecular microbiology, 110(2):296-308.

Flagellated spores play important roles in the infection of plants and animals by many eukaryotic microbes. The oomycete Phytophthora infestans, which causes potato blight, expresses two phosphagen kinases (PKs). These enzymes store energy in taurocyamine, and are hypothesized to resolve spatial and temporal imbalances between rates of ATP creation and use in zoospores. A dimeric PK is found at low levels in vegetative mycelia, but high levels in ungerminated sporangia and zoospores. In contrast, a monomeric PK protein is at similar levels in all tissues, although is transcribed primarily in mycelia. Subcellular localization studies indicate that the monomeric PK is mitochondrial. In contrast, the dimeric PK is cytoplasmic in mycelia and sporangia but is retargeted to flagellar axonemes during zoosporogenesis. This supports a model in which PKs shuttle energy from mitochondria to and through flagella. Metabolite analysis indicates that deployment of the flagellar PK is coordinated with a large increase in taurocyamine, synthesized by sporulation-induced enzymes that were lost during the evolution of zoospore-lacking oomycetes. Thus, PK function is enabled by coordination of the transcriptional, metabolic and protein targeting machinery during the life cycle. Since plants lack PKs, the enzymes may be useful targets for inhibitors of oomycete plant pathogens.

RevDate: 2018-09-28

Betts HC, Puttick MN, Clark JW, et al (2018)

Integrated genomic and fossil evidence illuminates life's early evolution and eukaryote origin.

Nature ecology & evolution, 2(10):1556-1562.

Establishing a unified timescale for the early evolution of Earth and life is challenging and mired in controversy because of the paucity of fossil evidence, the difficulty of interpreting it and dispute over the deepest branching relationships in the tree of life. Surprisingly, it remains perhaps the only episode in the history of life where literal interpretations of the fossil record hold sway, revised with every new discovery and reinterpretation. We derive a timescale of life, combining a reappraisal of the fossil material with new molecular clock analyses. We find the last universal common ancestor of cellular life to have predated the end of late heavy bombardment (>3.9 billion years ago (Ga)). The crown clades of the two primary divisions of life, Eubacteria and Archaebacteria, emerged much later (<3.4 Ga), relegating the oldest fossil evidence for life to their stem lineages. The Great Oxidation Event significantly predates the origin of modern Cyanobacteria, indicating that oxygenic photosynthesis evolved within the cyanobacterial stem lineage. Modern eukaryotes do not constitute a primary lineage of life and emerged late in Earth's history (<1.84 Ga), falsifying the hypothesis that the Great Oxidation Event facilitated their radiation. The symbiotic origin of mitochondria at 2.053-1.21 Ga reflects a late origin of the total-group Alphaproteobacteria to which the free living ancestor of mitochondria belonged.

RevDate: 2018-08-19

Radzinski M, D Reichmann (2018)

Variety is the spice of life: how to explore a redox-dependent heterogeneity in genomically identical cellular populations.

Current genetics pii:10.1007/s00294-018-0878-9 [Epub ahead of print].

Cellular heterogeneity is a widespread phenomenon, existing across organisms and serving a crucial role in evolution and cell survival. Genetically identical cells may as a result present in a variety of forms with different gene and protein expressions, as well as oxidation level. As a result, a wide range of methodologies and techniques for dissecting different types of genetic, proteomic, and phenotypic heterogeneous traits have emerged in recent years in an effort to better understand how diversity exists within a single population and its effects therein. A key area of interest seeks to establish the ways in which cellular heterogeneity and aging processes interact with each other. Here, we discuss recent developments in defining cellular heterogeneity, specifically focusing on redox-dependent heterogeneity, its characterization, quantification, and behavior. We further expand on potential applications of a cell sorting-based methodology for distinguishing between cells harboring different redox statuses. As an example, we use organelle-specific fluorescence protein-based probes to examine the crosstalk between cytosol and mitochondria in a yeast strain lacking glutathione reductase. Together, these may have wide-reaching implications for future research into redox-associated factors, as well as mechanisms of redox-dependent heterogeneity and its influence on organelles and the cell at large.

RevDate: 2018-08-15

Vazquez JM, Sulak M, Chigurupati S, et al (2018)

A Zombie LIF Gene in Elephants Is Upregulated by TP53 to Induce Apoptosis in Response to DNA Damage.

Cell reports, 24(7):1765-1776.

Large-bodied organisms have more cells that can potentially turn cancerous than small-bodied organisms, imposing an increased risk of developing cancer. This expectation predicts a positive correlation between body size and cancer risk; however, there is no correlation between body size and cancer risk across species ("Peto's paradox"). Here, we show that elephants and their extinct relatives (proboscideans) may have resolved Peto's paradox in part through refunctionalizing a leukemia inhibitory factor pseudogene (LIF6) with pro-apoptotic functions. LIF6 is transcriptionally upregulated by TP53 in response to DNA damage and translocates to the mitochondria where it induces apoptosis. Phylogenetic analyses of living and extinct proboscidean LIF6 genes indicates that its TP53 response element evolved coincident with the evolution of large body sizes in the proboscidean stem lineage. These results suggest that refunctionalizing of a pro-apoptotic LIF pseudogene may have been permissive (although not sufficient) for the evolution of large body sizes in proboscideans.

RevDate: 2018-08-17

Wideman JG, Balacco DL, Fieblinger T, et al (2018)

PDZD8 is not the 'functional ortholog' of Mmm1, it is a paralog.

F1000Research, 7:1088.

Authors of a recent paper demonstrate that, like ERMES (ER-mitochondria encounter structure) in fungal cells, PDZD8 (PDZ domain containing 8) tethers mitochondria to the ER in mammalian cells. However, identifying PDZD8 as a "functional ortholog" of yeast Mmm1 (maintenance of mitochondrial morphology protein 1) is at odds with the phylogenetic data. PDZD8 and Mmm1 are paralogs, not orthologs, which affects the interpretation of the data with respect to the evolution of ER-mitochondria tethering. Our phylogenetic analyses show that PDZD8 co-occurs with ERMES components in lineages closely related to animals solidifying its identity as a paralog of Mmm1. Additionally, we identify two related paralogs, one specific to flagellated fungi, and one present only in unicellular relatives of animals. These results point to a complex evolutionary history of ER-mitochondria tethering involving multiple gene gains and losses in the lineage leading to animals and fungi.

RevDate: 2018-10-25
CmpDate: 2018-10-25

Dong S, Zhao C, Chen F, et al (2018)

The complete mitochondrial genome of the early flowering plant Nymphaea colorata is highly repetitive with low recombination.

BMC genomics, 19(1):614 pii:10.1186/s12864-018-4991-4.

BACKGROUND: Mitochondrial genomes of flowering plants (angiosperms) are highly dynamic in genome structure. The mitogenome of the earliest angiosperm Amborella is remarkable in carrying rampant foreign DNAs, in contrast to Liriodendron, the other only known early angiosperm mitogenome that is described as 'fossilized'. The distinctive features observed in the two early flowering plant mitogenomes add to the current confusions of what early flowering plants look like. Expanded sampling would provide more details in understanding the mitogenomic evolution of early angiosperms. Here we report the complete mitochondrial genome of water lily Nymphaea colorata from Nymphaeales, one of the three orders of the earliest angiosperms.

RESULTS: Assembly of data from Pac-Bio long-read sequencing yielded a circular mitochondria chromosome of 617,195 bp with an average depth of 601×. The genome encoded 41 protein coding genes, 20 tRNA and three rRNA genes with 25 group II introns disrupting 10 protein coding genes. Nearly half of the genome is composed of repeated sequences, which contributed substantially to the intron size expansion, making the gross intron length of the Nymphaea mitochondrial genome one of the longest among angiosperms, including an 11.4-Kb intron in cox2, which is the longest organellar intron reported to date in plants. Nevertheless, repeat mediated homologous recombination is unexpectedly low in Nymphaea evidenced by 74 recombined reads detected from ten recombinationally active repeat pairs among 886,982 repeat pairs examined. Extensive gene order changes were detected in the three early angiosperm mitogenomes, i.e. 38 or 44 events of inversions and translocations are needed to reconcile the mitogenome of Nymphaea with Amborella or Liriodendron, respectively. In contrast to Amborella with six genome equivalents of foreign mitochondrial DNA, not a single horizontal gene transfer event was observed in the Nymphaea mitogenome.

CONCLUSIONS: The Nymphaea mitogenome resembles the other available early angiosperm mitogenomes by a similarly rich 64-coding gene set, and many conserved gene clusters, whereas stands out by its highly repetitive nature and resultant remarkable intron expansions. The low recombination level in Nymphaea provides evidence for the predominant master conformation in vivo with a highly substoichiometric set of rearranged molecules.

RevDate: 2018-10-01
CmpDate: 2018-10-01

Reyes-Ramos CA, Peregrino-Uriarte AB, Cota-Ruiz K, et al (2018)

Phosphoenolpyruvate carboxykinase cytosolic and mitochondrial isoforms are expressed and active during hypoxia in the white shrimp Litopenaeus vannamei.

Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology, 226:1-9.

Hypoxic zones in marine environments are spreading around the world affecting the survival of many organisms. Marine animals have several strategies to respond to hypoxia, including the regulation of gluconeogenesis. Phosphoenolpyruvate carboxykinase (PEPCK) is a key regulatory enzyme of gluconeogenesis. The objective of this work was to study two isoforms of PEPCK, one mitochondrial (PEPKC-M) and one cytosolic (PEPCK-C), from the white shrimp Litopenaeus vannamei and the response to hypoxia. Both PEPCK isoforms are 72 kDa proteins and have 92% identity at the amino acid level. The mitochondrial isoform has a N-terminal signal peptide for mitochondrial import. Gene expression and enzymatic activity in subcellular fractions were detected in gills, hepatopancreas and muscle in normoxic and hypoxic conditions. Expression of PEPCK-C was higher than PEPCK-M in all the tissues and induced in response to hypoxia at 48 h in hepatopancreas, while the enzymatic activity of PEPCK-M was higher than PEPCK-C in gills and hepatopancreas, but not in muscle and also increased in response to hypoxia in hepatopancreas but decreased in gills and muscle. During limiting oxygen conditions, shrimp tissues obtain energy by inducing anaerobic glycolysis, and although gluconeogenesis implies energy investment, due to the need to maintain glucose homeostasis, these gluconeogenic enzymes are active with contrasting behaviors in the cytosol and mitochondrial cell compartments and appear to be up-regulated in hepatopancreas indicating this tissue pivotal role in gluconeogenesis during the response to hypoxia.

RevDate: 2018-10-25
CmpDate: 2018-10-25

Ding CQ, Ng S, Wang L, et al (2018)

Genome-wide identification and characterization of ALTERNATIVE OXIDASE genes and their response under abiotic stresses in Camellia sinensis (L.) O. Kuntze.

Planta, 248(5):1231-1247.

MAIN CONCLUSION: Four typical ALTERNATIVE OXIDASE genes have been identified in tea plants, and their sequence features and gene expression profiles have provided useful information for further studies on function and regulation. Alternative oxidase (AOX) is a terminal oxidase located in the respiratory electron transport chain. AOX catalyzes the oxidation of quinol and the reduction of oxygen into water. In this study, a genome-wide search and subsequent DNA cloning were performed to identify and characterize AOX genes in tea plant (Camellia sinensis (L.) O. Kuntze cv. Longjing43). Our results showed that tea plant possesses four AOX genes, i.e., CsAOX1a, CsAOX1d, CsAOX2a and CsAOX2b. Gene structure and protein sequence analyses revealed that all CsAOXs share a four-exon/three-intron structure with highly conserved regions and amino acid residues, which are necessary for AOX secondary structures, catalytic activities and post-translational regulations. All CsAOX were shown to localize in mitochondria using the green fluorescent protein (GFP)-targeting assay. Both CsAOX1a and CsAOX1d were induced by cold, salt and drought stresses, and with different expression patterns in young and mature leaves. Reactive oxygen species (ROS) accumulated strongly after 72 and 96 h cold treatments in both young and mature leaves, while the polyphenol and total catechin decreased significantly only in mature leaves. In comparison to AtAOX1a in Arabidopsis thaliana, CsAOX1a lost almost all of the stress-responsive cis-acting regulatory elements in its promoter region (1500 bp upstream), but possesses a flavonoid biosynthesis-related MBSII cis-acting regulatory element. These results suggest a link between CsAOX1a function and the metabolism of some secondary metabolites in tea plant. Our studies provide a basis for the further elucidation of the biological function and regulation of the AOX pathway in tea plants.

RevDate: 2018-10-08
CmpDate: 2018-10-08

Skoracka A, Lopes LF, Alves MJ, et al (2018)

Genetics of lineage diversification and the evolution of host usage in the economically important wheat curl mite, Aceria tosichella Keifer, 1969.

BMC evolutionary biology, 18(1):122 pii:10.1186/s12862-018-1234-x.

BACKGROUND: Understanding the mechanisms that underlie the diversification of herbivores through interactions with their hosts is important for their diversity assessment and identification of expansion events, particularly in a human-altered world where evolutionary processes can be exacerbated. We studied patterns of host usage and genetic structure in the wheat curl mite complex (WCM), Aceria tosichella, a major pest of the world's grain industry, to identify the factors behind its extensive diversification.

RESULTS: We expanded on previous phylogenetic research, demonstrating deep lineage diversification within the taxon, a complex of distinctive host specialist and generalist lineages more diverse than previously assumed. Time-calibrated phylogenetic reconstruction inferred from mitochondrial DNA sequence data suggests that lineage diversification pre-dates the influence of agricultural practices, and lineages started to radiate in the mid Miocene when major radiations of C4 grasses is known to have occurred. Furthermore, we demonstrated that host specificity is not phylogenetically constrained, while host generalization appears to be a more derived trait coinciding with the expansion of the world's grasslands. Demographic history of specialist lineages have been more stable when compared to generalists, and their expansion pre-dated all generalist lineages. The lack of host-associated genetic structure of generalists indicates gene flow between mite populations from different hosts.

CONCLUSIONS: Our analyses demonstrated that WCM is an unexpectedly diverse complex of genetic lineages and its differentiation is likely associated with the time of diversification and expansion of its hosts. Signatures of demographic histories and expansion of generalists are consistent with the observed proliferation of the globally most common lineages. The apparent lack of constrains on host use, coupled with a high colonization potential, hinders mite management, which may be further compromised by host range expansion. This study provides a significant contribution to the growing literature on host-association and diversification in herbivorous invertebrates.

RevDate: 2018-07-31

Torrezan-Nitao E, Figueiredo RCBQ, LF Marques-Santos (2018)

Mitochondrial permeability transition pore in sea urchin female gametes.

Mechanisms of development pii:S0925-4773(18)30068-6 [Epub ahead of print].

Mitochondrial permeability transition pore (MPTP) has been associated to calcium homeostasis and reactive oxygen species (ROS) generation in several cell types. While extensively investigated in somatic cells, there are few data regarding MPTP phenomenon in gametes. The aim of the present work was to investigate MPTP occurrence in sea urchin female gametes. The protonophores CCCP and FCCP, and the Ca2+ ionophore ionomycin, were used as pore inductors. Pore opening was monitored by mitochondrial potential sensitive probes and cobalt-quenched calcein assay. The pore desensitizer cyclosporin A (CsA) prevented the loss of mitochondrial inner membrane potential (ΔΨm) and pore opening induced by MPTP activators. The disruption of ΔΨm led to an increase in ROS generation, which was completely prevented by CsA. Our data also demonstrated that the increase in ROS production induced by MPTP opening requires extracellular Ca2+. In summary, the current study provides evidence about the occurrence of MPTP in sea urchin eggs in a similar manner as described in vertebrate somatic cells - CsA-sensitive, voltage- and Ca2+-triggered - and shows MPTP as a highly conserved physiological event through the evolution.

RevDate: 2018-08-09

Dhir A, Dhir S, Borowski LS, et al (2018)

Mitochondrial double-stranded RNA triggers antiviral signalling in humans.

Nature, 560(7717):238-242.

Mitochondria are descendants of endosymbiotic bacteria and retain essential prokaryotic features such as a compact circular genome. Consequently, in mammals, mitochondrial DNA is subjected to bidirectional transcription that generates overlapping transcripts, which are capable of forming long double-stranded RNA structures1,2. However, to our knowledge, mitochondrial double-stranded RNA has not been previously characterized in vivo. Here we describe the presence of a highly unstable native mitochondrial double-stranded RNA species at single-cell level and identify key roles for the degradosome components mitochondrial RNA helicase SUV3 and polynucleotide phosphorylase PNPase in restricting the levels of mitochondrial double-stranded RNA. Loss of either enzyme results in massive accumulation of mitochondrial double-stranded RNA that escapes into the cytoplasm in a PNPase-dependent manner. This process engages an MDA5-driven antiviral signalling pathway that triggers a type I interferon response. Consistent with these data, patients carrying hypomorphic mutations in the gene PNPT1, which encodes PNPase, display mitochondrial double-stranded RNA accumulation coupled with upregulation of interferon-stimulated genes and other markers of immune activation. The localization of PNPase to the mitochondrial inter-membrane space and matrix suggests that it has a dual role in preventing the formation and release of mitochondrial double-stranded RNA into the cytoplasm. This in turn prevents the activation of potent innate immune defence mechanisms that have evolved to protect vertebrates against microbial and viral attack.

RevDate: 2018-07-27

Riggs CL, Summers A, Warren DE, et al (2018)

Small Non-coding RNA Expression and Vertebrate Anoxia Tolerance.

Frontiers in genetics, 9:230.

Background: Extreme anoxia tolerance requires a metabolic depression whose modulation could involve small non-coding RNAs (small ncRNAs), which are specific, rapid, and reversible regulators of gene expression. A previous study of small ncRNA expression in embryos of the annual killifish Austrofundulus limnaeus, the most anoxia-tolerant vertebrate known, revealed a specific expression pattern of small ncRNAs that could play important roles in anoxia tolerance. Here, we conduct a comparative study on the presence and expression of small ncRNAs in the most anoxia-tolerant representatives of several major vertebrate lineages, to investigate the evolution of and mechanisms supporting extreme anoxia tolerance. The epaulette shark (Hemiscyllium ocellatum), crucian carp (Carassius carassius), western painted turtle (Chrysemys picta bellii), and leopard frog (Rana pipiens) were exposed to anoxia and recovery, and small ncRNAs were sequenced from the brain (one of the most anoxia-sensitive tissues) prior to, during, and following exposure to anoxia. Results: Small ncRNA profiles were broadly conserved among species under normoxic conditions, and these expression patterns were largely conserved during exposure to anoxia. In contrast, differentially expressed genes are mostly unique to each species, suggesting that each species may have evolved distinct small ncRNA expression patterns in response to anoxia. Mitochondria-derived small ncRNAs (mitosRNAs) which have a robust response to anoxia in A. limnaeus embryos, were identified in the other anoxia tolerant vertebrates here but did not display a similarly robust response to anoxia. Conclusion: These findings support an overall stabilization of the small ncRNA transcriptome during exposure to anoxic insults, but also suggest that multiple small ncRNA expression pathways may support anoxia tolerance, as no conserved small ncRNA response was identified among the anoxia-tolerant vertebrates studied. This may reflect divergent strategies to achieve the same endpoint: anoxia tolerance. However, it may also indicate that there are multiple cellular pathways that can trigger the same cellular and physiological survival processes, including hypometabolism.

RevDate: 2018-07-22

Lang SA, DH Shain (2018)

Atypical Evolution of the F1Fo Adenosine Triphosphate Synthase Regulatory ATP6 subunit in Glacier Ice Worms (Annelida: Clitellata: Mesenchytraeus).

Evolutionary bioinformatics online, 14:1176934318788076 pii:10.1177_1176934318788076.

The glacier ice worm, Mesenchytraeus solifugus, is among a few animals that reside permanently in glacier ice. Their adaptation to cold temperature has been linked to relatively high intracellular adenosine triphosphate (ATP) levels, which compensate for reductions in molecular motion at low physiological temperatures. Here, we show that ATP6-the critical regulatory subunit of the F1Fo-ATP synthase and primary target of mitochondrial disease-acquired an unprecedented histidine-rich, 18-amino acid carboxy-terminal extension, which counters the strong evolutionary trend of mitochondrial genome compaction. Furthermore, sequence analysis suggests that this insertion is not of metazoan origin, but rather is a product of horizontal gene transfer from a microbial dietary source, and may act as a proton shuttle to accelerate the rate of ATP synthesis.

RevDate: 2018-09-13
CmpDate: 2018-09-13

Sun S, Sha Z, Y Wang (2018)

Complete mitochondrial genome of the first deep-sea spongicolid shrimp Spongiocaris panglao (Decapoda: Stenopodidea): Novel gene arrangement and the phylogenetic position and origin of Stenopodidea.

Gene, 676:123-138.

Stenopodidea Claus, 1872 (Crustacea: Decapoda) is one of the major groups of decapods crustaceans. Hitherto, only one complete mitochondrial genome (mitogenome) from the family Stenopodidae is available for the infraorder Stenopodidea. Here, we determined the complete mitogenome of Spongiocaris panglao de Grave and Saito, 2016 using Illumina sequencing, representing the first species from the family Spongicolidae. The 15,909 bp genome is a circular molecule and consists of 13 protein-coding genes (PCGs), 2 ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes and one control region. Although the overall genome organization is typical for metazoans, the mitogenome of S. panglao shows some derived characters. A + T content of 77.42% in S. pamglao mitogenome is second-highest among the dacapods described to date. The trnR gene exhibit modified secondary structure with the TψC loop completely missing, which might be a putative autapomorphy of S. pamglao mitogenome. Compared with the shallow-water stenopodidean species S. hispidus, the control region of S. pamglao exhibits three characteristics: larger size, higher A + T content, and more tandem repeat sequences. The gene order exhibited difference from the ancestral mitogenome pattern of the Pancrustacea, with 5 tRNA genes rearrangement. The result from BI was agreed with most morphological characters and molecular evidences, revealing that Stenopodidea and Reptantia had the closest relationship, as the sister group of Caridea. Still, the alternative hypothesis supported from ML topology cannot be completely rejected based on the current data. Estimated times revealed that the two stenopodideans families Stenopodidae and Spongicolidae diverged from each other around 122 Mya. The divergence time of spongicolid shrimp is in good agreement with the origin of their hexactinellid hosts (78-144 Mya).

RevDate: 2018-08-18

Katane M, Ariyoshi M, Tateishi S, et al (2018)

Structural and enzymatic properties of mammalian d-glutamate cyclase.

Archives of biochemistry and biophysics, 654:10-18.

d-Glutamate cyclase (DGLUCY) is a unique enzyme that reversibly converts free d-glutamate to 5-oxo-d-proline and H2O. Mammalian DGLUCY is highly expressed in the mitochondrial matrix in the heart, and its downregulation disrupts d-glutamate and/or 5-oxo-d-proline levels, contributing to the onset and/or exacerbation of heart failure. However, detailed characterisation of DGLUCY has not yet been performed. Herein, the structural and enzymatic properties of purified recombinant mouse DGLUCY were examined. The results revealed a dimeric oligomerisation state, and both d-glutamate-to-5-oxo-d-proline and 5-oxo-d-proline-to-d-glutamate reactions were catalysed in a stereospecific manner. Catalytic activity is modulated by divalent cations and nucleotides including ATP and ADP. Interestingly, the presence of Mn2+ completely abolished the 5-oxo-d-proline-to-d-glutamate reaction but stimulated the d-glutamate-to-5-oxo-d-proline reaction. The optimum pH is ∼8.0, similar to that in the mitochondrial matrix, and the catalytic efficiency for d-glutamate is markedly higher than that for 5-oxo-d-proline. These findings suggest that DGLUCY functions as a metalloenzyme that degrades d-glutamate in the mitochondrial matrix in mammalian cells. The results also provide insight into the correlation between DGLUCY enzyme activity and the physiological and pathological roles of d-glutamate and 5-oxo-d-proline in cardiac function, which is of relevance to the risk of onset of heart failure.

RevDate: 2018-07-11

Kasperski A, R Kasperska (2018)

Bioenergetics of life, disease and death phenomena.

Theory in biosciences = Theorie in den Biowissenschaften pii:10.1007/s12064-018-0266-5 [Epub ahead of print].

In this article, some new aspects of unified cell bioenergetics are presented. From the perspective of unified cell bioenergetics certain subsequent stages of cancer development, from initiation stage, through transformation to metastasis, are analyzed. Here we show that after transformation, cancer cells are permanently exposed to reactive oxygen species, that causes continual random DNA mutations and as a result genome and chromosomal destabilizations. The modern cancer attractor hypothesis has been extended in explaining cancer development. Discussion is conducted in light of current cancerogenesis research, including bioenergetic cancer initiation, the somatic mutation theory and the tissue organization field theory. In the article reasons complicating the discovery of patterns of cancer genome changes and cancer evolution are presented. In addition certain cancer therapeutic aspects are given attention to.

RevDate: 2018-10-02

Iha C, Grassa CJ, Lyra GM, et al (2018)

Organellar genomics: a useful tool to study evolutionary relationships and molecular evolution in Gracilariaceae (Rhodophyta).

Journal of phycology [Epub ahead of print].

Gracilariaceae has a worldwide distribution including numerous economically important species. We applied high-throughput sequencing to obtain organellar genomes (mitochondria and chloroplast) from 10 species of Gracilariaceae and, combined with published genomes, to infer phylogenies and compare genome architecture among species representing main lineages. We obtained similar topologies between chloroplast and mitochondrial genomes phylogenies. However, the chloroplast phylogeny was better resolved with full support. In this phylogeny, Melanthalia intermedia is sister to a monophyletic clade including Gracilaria and Gracilariopsis, which were both resolved as monophyletic genera. Mitochondrial and chloroplast genomes were highly conserved in gene synteny, and variation mainly occurred in regions where insertions of plasmid-derived sequences (PDS) were found. In mitochondrial genomes, PDS insertions were observed in two regions where the transcription direction changes: between the genes cob and trnL, and trnA and trnN. In chloroplast genomes, PDS insertions were in different positions, but generally found between psdD and rrs genes. Gracilariaceae is a good model system to study the impact of PDS in genome evolution due to the frequent presence of these insertions in organellar genomes. Furthermore, the bacterial leuC/leuD operon was found in chloroplast genomes of Gracilaria tenuistipitata, G. chilensis, and M. intermedia, and in extrachromosomal plasmid of G. vermiculophylla. Phylogenetic trees show two different origins of leuC/leuD: genes found in chloroplast and plasmid were placed with proteobacteria, and genes encoded in the nucleus were close to Viridiplantae and cyanobacteria.

RevDate: 2018-07-10

Rolland N, Bouchnak I, Moyet L, et al (2018)

The Main Functions of Plastids.

Methods in molecular biology (Clifton, N.J.), 1829:73-85.

Plastids are semiautonomous organelles like mitochondria, and derive from a cyanobacterial ancestor that was engulfed by a host cell. During evolution, they have recruited proteins originating from the nuclear genome, and only parts of their ancestral metabolic properties were conserved and optimized to limit functional redundancy with other cell compartments. Furthermore, large disparities in metabolic functions exist among various types of plastids, and the characterization of their various metabolic properties is far from being accomplished. In this review, we provide an overview of the main functions, known to be achieved by plastids or shared by plastids and other compartments of the cell. In short, plastids appear at the heart of all main plant functions.

RevDate: 2018-07-10

Maréchal E (2018)

Primary Endosymbiosis: Emergence of the Primary Chloroplast and the Chromatophore, Two Independent Events.

Methods in molecular biology (Clifton, N.J.), 1829:3-16.

The emergence of semiautonomous organelles, such as the mitochondrion, the chloroplast, and more recently, the chromatophore, are critical steps in the evolution of eukaryotes. They resulted from primary endosymbiotic events that seem to share general features, i.e., an acquisition of a bacterium/cyanobacteria likely via a phagocytic membrane, a genome reduction coinciding with an escape of genes from the organelle to the nucleus, and finally the appearance of an active system translocating nuclear-encoded proteins back to the organelles. An intense mobilization of foreign genes of bacterial origin, via horizontal gene transfers, plays a critical role. Some third partners, like Chlamydia, might have facilitated the transition from cyanobacteria to the early chloroplast. This chapter describes our current understanding of primary endosymbiosis, with a specific focus on primary chloroplasts considered to have emerged more than one billion years ago, and on the chromatophore, having emerged about one hundred million years ago.

RevDate: 2018-07-11

MacDonald JA, Fowle WH, Shin E, et al (2018)

A method for freeze-fracture and scanning electron microscopy of isolated mitochondria.

MethodsX, 5:593-598 pii:S2215-0161(18)30072-4.

Electron microscopy as a methodology for the study of mitochondria based on morphological features is a standard technique that has experienced little evolution over the course of several decades. This technology has identified heterogeneity of mitochondria populations across both whole tissues, as well between individual cells, using primarily ultrathin sections for transmission electron microscopy (TEM). However, this technique constrains the evaluation of a sample to a single two-dimensional plane. To overcome this limitation, scanning electron microscopy (SEM) has been successfully utilized to observe three-dimensional mitochondria structures within the complex microenvironment containing total cellular components. In response to these dual technical caveats of existing electron microscopy protocols, we developed a methodology to evaluate the three-dimensional ultrastructure of isolated mitochondria, utilizing a freeze-fracture step and rigorous preservation of sample morphology. This protocol allows for a more high-throughput analysis of mitochondria populations from a specimen of interest, as the sample has been previously purified, as well as a finer resolution of complex intra-mitochondrial structures, using the depth of field created by SEM. •Protocol designed for SEM of isolated mitochondria samples.•SEM visualizes mitochondria ultrastructure in 3-D.•Freeze-fracture creates cross-sectional plane for view of interior organelle structures.

RevDate: 2018-09-18
CmpDate: 2018-08-13

He K, Chen X, Chen P, et al (2018)

A new genus of Asiatic short-tailed shrew (Soricidae, Eulipotyphla) based on molecular and morphological comparisons.

Zoological research, 39(5):321-334.

Blarinellini is a tribe of soricine shrews comprised of nine fossil genera and one extant genus. Blarinelline shrews were once widely distributed throughout Eurasia and North America, though only members of the Asiatic short-tailed shrew genus Blarinella currently persist (mostly in southwestern China and adjacent areas). Only three forms of Blarinella have been recognized as either species or subspecies. However, recent molecular studies indicated a strikingly deep divergence within the genus, implying the existence of a distinct genus-level lineage. We sequenced the complete mitochondrial genomes and one nuclear gene of three Asiatic short-tailed and two North American shrews and analyzed them morphometrically and morphologically. Our molecular analyses revealed that specimens ascribed to B. griselda formed two deeply diverged lineages, one a close relative to B. quadraticauda, whereas the other - comprised of topotype specimens from southern Gansu - diverged from other Blarinella in the middle Miocene (ca. 18.2 million years ago (Ma), 95% confidence interval=13.4-23.6 Ma). Although the skulls were similarly shaped in both lineages, we observed several diagnostic characteristics, including the shape of the upper P4. In consideration of the molecular and morphological evidence, we recognize B. griselda as the sole species of a new genus, namely, Pantherina gen. nov. Interestingly, some characteristics of Pantherina griselda are more similar to fossil genera, suggesting it represents an evolutionarily more primitive form than Blarinella. Recognition of this new genus sheds light on the systematics and evolutionary history of the tribe Blarinellini throughout Eurasia and North America.

RevDate: 2018-07-10

Lenz H, Hein A, V Knoop (2018)

Plant organelle RNA editing and its specificity factors: enhancements of analyses and new database features in PREPACT 3.0.

BMC bioinformatics, 19(1):255 pii:10.1186/s12859-018-2244-9.

BACKGROUND: Gene expression in plant chloroplasts and mitochondria is affected by RNA editing. Numerous C-to-U conversions, accompanied by reverse U-to-C exchanges in some plant clades, alter the genetic information encoded in the organelle genomes. Predicting and analyzing RNA editing, which ranges from only few sites in some species to thousands in other taxa, is bioinformatically demanding.

RESULTS: Here, we present major enhancements and extensions of PREPACT, a WWW-based service for analysing, predicting and cataloguing plant-type RNA editing. New features in PREPACT's core include direct GenBank accession query input and options to restrict searches to candidate U-to-C editing or to sites where editing has been documented previously in the references. The reference database has been extended by 20 new organelle editomes. PREPACT 3.0 features new modules "EdiFacts" and "TargetScan". EdiFacts integrates information on pentatricopeptide repeat (PPR) proteins characterized as site-specific RNA editing factors. PREPACT's editome references connect into EdiFacts, linking editing events to specific co-factors where known. TargetScan allows position-weighted querying for sequence motifs in the organelle references, optionally restricted to coding regions or sequences around editing sites, or in queries uploaded by the user. TargetScan is mainly intended to evaluate and further refine the proposed PPR-RNA recognition code but may be handy for other tasks as well. We present an analysis for the immediate sequence environment of more than 15,000 documented editing sites finding strong and different bias in the editome data sets.

CONCLUSIONS: We exemplarily present the novel features of PREPACT 3.0 aimed to enhance the analyses of plant-type RNA editing, including its new modules EdiFacts integrating information on characterized editing factors and TargetScan aimed to analyse RNA editing site recognition specificities.

RevDate: 2018-09-18
CmpDate: 2018-08-13

Liu SY, He K, Chen SD, et al (2018)

How many species of Apodemus and Rattus occur in China? A survey based on mitochondrial cyt b and morphological analyses.

Zoological research, 39(5):309-320.

Apodemus (mice) and Rattus (rats) are the top rodent reservoirs for zoonoses in China, yet little is known about their diversity. We reexamined the alpha diversity of these two genera based on a new collection of specimens from China and their cyt b sequences in GenBank. We also tested whether species could be identified using external and craniodental measurements exclusively. Measurements from 147 specimens of Apodemus and 236 specimens of Rattus were used for morphological comparisons. We analysed 74 cyt b sequences of Apodemus and 100 cyt b sequences of Rattus to facilitate phylogenetic estimations. Results demonstrated that nine species of Apodemus and seven species of Rattus, plus a new subspecies of Rattus nitidus, are distributed in China. Principal component analysis using external and craniodental measurements revealed that measurements alone could not separate the recognized species. The occurrence of Rattus pyctoris in China remains uncertain.

RevDate: 2018-06-28

Woodling NS, L Partridge (2018)

Parkinson's Disease: Mitochondria Parked at the ER Hit the Snooze Button.

Neuron, 98(6):1059-1061.

Parkinson's disease patients report sleep disturbances well ahead of motor symptoms. In this issue of Neuron, Valadas et al. (2018) report that the disease genes pink1 and parkin exert novel, cell-type-specific effects to modulate ER-mitochondria contacts, neuropeptidergic transmission, and sleep patterns.

RevDate: 2018-08-26
CmpDate: 2018-08-24

Bilz NC, Jahn K, Lorenz M, et al (2018)

Rubella Viruses Shift Cellular Bioenergetics to a More Oxidative and Glycolytic Phenotype with a Strain-Specific Requirement for Glutamine.

Journal of virology, 92(17): pii:JVI.00934-18.

The flexible regulation of cellular metabolic pathways enables cellular adaptation to changes in energy demand under conditions of stress such as posed by a virus infection. To analyze such an impact on cellular metabolism, rubella virus (RV) was used in this study. RV replication under selected substrate supplementation with glucose, pyruvate, and glutamine as essential nutrients for mammalian cells revealed its requirement for glutamine. The assessment of the mitochondrial respiratory (based on the oxygen consumption rate) and glycolytic (based on the extracellular acidification rate) rate and capacity by respective stress tests through Seahorse technology enabled determination of the bioenergetic phenotype of RV-infected cells. Irrespective of the cellular metabolic background, RV infection induced a shift of the bioenergetic state of epithelial cells (Vero and A549) and human umbilical vein endothelial cells to a higher oxidative and glycolytic level. Interestingly there was a RV strain-specific, but genotype-independent demand for glutamine to induce a significant increase in metabolic activity. While glutaminolysis appeared to be rather negligible for RV replication, glutamine could serve as donor of its amide nitrogen in biosynthesis pathways for important metabolites. This study suggests that the capacity of RVs to induce metabolic alterations could evolve differently during natural infection. Thus, changes in cellular bioenergetics represent an important component of virus-host interactions and could complement our understanding of the viral preference for a distinct host cell population.IMPORTANCE RV pathologies, especially during embryonal development, could be connected with its impact on mitochondrial metabolism. With bioenergetic phenotyping we pursued a rather novel approach in virology. For the first time it was shown that a virus infection could shift the bioenergetics of its infected host cell to a higher energetic state. Notably, the capacity to induce such alterations varied among different RV isolates. Thus, our data add viral adaptation of cellular metabolic activity to its specific needs as a novel aspect to virus-host evolution. In addition, this study emphasizes the implementation of different viral strains in the study of virus-host interactions and the use of bioenergetic phenotyping of infected cells as a biomarker for virus-induced pathological alterations.

RevDate: 2018-08-27

Yoshida Y (2018)

The cellular machineries responsible for the division of endosymbiotic organelles.

Journal of plant research, 131(5):727-734.

Chloroplasts (plastids) and mitochondria evolved from endosymbiotic bacteria. These organelles perform vital functions in photosynthetic eukaryotes, such as harvesting and converting energy for use in biological processes. Consistent with their evolutionary origins, plastids and mitochondria proliferate by the binary fission of pre-existing organelles. Here, I review the structures and functions of the supramolecular machineries driving plastid and mitochondrial division, which were discovered and first studied in the primitive red alga Cyanidioschyzon merolae. In the past decade, intact division machineries have been isolated from plastids and mitochondria and examined to investigate their underlying structure and molecular mechanisms. A series of studies has elucidated how these division machineries assemble and transform during the fission of these organelles, and which of the component proteins generate the motive force for their contraction. Plastid- and mitochondrial-division machineries have important similarities in their structures and mechanisms despite sharing no component proteins, implying that these division machineries evolved in parallel. The establishment of these division machineries might have enabled the host eukaryotic ancestor to permanently retain these endosymbiotic organelles by regulating their binary fission and the equal distribution of resources to daughter cells. These findings provide key insights into the establishment of endosymbiotic organelles and have opened new avenues of research into their evolution and mechanisms of proliferation.

RevDate: 2018-10-22
CmpDate: 2018-10-22

van der Sluis R (2018)

Analyses of the genetic diversity and protein expression variation of the acyl: CoA medium-chain ligases, ACSM2A and ACSM2B.

Molecular genetics and genomics : MGG, 293(5):1279-1292.

Benzoate (found in milk and widely used as preservative), salicylate (present in fruits and the active component of aspirin), dietary polyphenols produced by gut microbiota, metabolites from organic acidemias, and medium-chain fatty acids (MCFAs) are all metabolised/detoxified by the glycine conjugation pathway. Xenobiotics are first activated to an acyl-CoA by the mitochondrial xenobiotic/medium-chain fatty acid: CoA ligases (ACSMs) and subsequently conjugated to glycine by glycine N-acyltransferase (GLYAT). The MCFAs are activated to acyl-CoA by the ACSMs before entering mitochondrial β-oxidation. This two-step enzymatic pathway has, however, not been thoroughly investigated and the biggest gap in the literature remains the fact that studies continuously characterise the pathway as a one-step reaction. There are no studies available on the interaction/competition of the various substrates involved in the pathway, whilst very little research has been done on the ACSM ligases. To identify variants/haplotypes that should be characterised in future detoxification association studies, this study assessed the naturally observed sequence diversity and protein expression variation of ACSM2A and ACSM2B. The allelic variation, haplotype diversity, Tajima's D values, and phylogenetic analyses indicated that ACSM2A and ACSM2B are highly conserved. This confirmed an earlier hypothesis that the glycine conjugation pathway is highly conserved and essential for life as it maintains the CoA and glycine homeostasis in the liver mitochondria. The protein expression analyses showed that ACSM2A is the predominant transcript in liver. Future studies should investigate the effect of the variants identified in this study on the substrate specificity of these proteins.

RevDate: 2018-06-27

Sharma M, Bennewitz B, RB Klösgen (2018)

Rather rule than exception? How to evaluate the relevance of dual protein targeting to mitochondria and chloroplasts.

Photosynthesis research pii:10.1007/s11120-018-0543-7 [Epub ahead of print].

Dual targeting of a nuclearly encoded protein into two different cell organelles is an exceptional event in eukaryotic cells. Yet, the frequency of such dual targeting is remarkably high in case of mitochondria and chloroplasts, the two endosymbiotic organelles of plant cells. In most instances, it is mediated by "ambiguous" transit peptides, which recognize both organelles as the target. A number of different approaches including in silico, in organello as well as both transient and stable in vivo assays are established to determine the targeting specificity of such transit peptides. In this review, we will describe and compare these approaches and discuss the potential role of this unusual targeting process. Furthermore, we will present a hypothetical scenario how dual targeting might have arisen during evolution.

RevDate: 2018-08-17

Barshad G, Marom S, Cohen T, et al (2018)

Mitochondrial DNA Transcription and Its Regulation: An Evolutionary Perspective.

Trends in genetics : TIG, 34(9):682-692.

The bacterial heritage of mitochondria, as well as its independent genome [mitochondrial DNA (mtDNA)] and polycistronic transcripts, led to the view that mitochondrial transcriptional regulation relies on an evolutionarily conserved, prokaryotic-like system that is separated from the rest of the cell. Indeed, mtDNA transcription was previously thought to be governed by a few dedicated direct regulators, namely, the mitochondrial RNA polymerase (POLRMT), two transcription factors (TFAM and TF2BM), one transcription elongation (TEFM), and one known transcription termination factor (mTERF1). Recent findings have, however, revealed that known nuclear gene expression regulators are also involved in mtDNA transcription and have identified novel transcriptional features consistent with adaptation of the mitochondria to the regulatory environment of the precursor of the eukaryotic cell. Finally, whereas mammals follow the human mtDNA transcription pattern, other organisms notably diverge in terms of mtDNA transcriptional regulation. Hence, mtDNA transcriptional regulation is likely more evolutionary diverse than once thought.

RevDate: 2018-09-21

Bize P, Lowe I, Lehto Hürlimann M, et al (2018)

Effects of the Mitochondrial and Nuclear Genomes on Nonshivering Thermogenesis in a Wild Derived Rodent.

Integrative and comparative biology, 58(3):532-543.

A key adaptation of mammals to their environment is their ability to maintain a constant high body temperature, even at rest, under a wide range of ambient temperatures. In cold climates, this is achieved by an adaptive production of endogenous heat, known as nonshivering thermogenesis (NST), in the brown adipose tissue (BAT). This organ, unique to mammals, contains a very high density of mitochondria, and BAT correct functioning relies on the correct functioning of its mitochondria. Mitochondria enclose proteins encoded both in the maternally inherited mitochondrial genome and in the biparentally inherited nuclear genome, and one overlooked hypothesis is that both genomes and their interaction may shape NST. By housing under standardized conditions wild-derived common voles (Microtus arvalis) from two distinct evolutionary lineages (Western [W] and Central [C]), we show that W voles had greater NST than C voles. By introgressing those two lineages over at least nine generations, we then experimentally tested the influence of the nuclear and mitochondrial genomes on NST and related phenotypic traits. We found that between-lineage variation in NST and BAT size were significantly influenced by the mitochondrial and nuclear genomes, respectively, with the W mitochondrial genotype being associated with higher NST and the W nuclear genotype with a larger BAT. There were significant mito-nuclear interactions on whole animal body weight and resting metabolic rate (RMR). Hybrid voles were lighter and had higher RMR. Overall, our findings turn new light on the influence of the mitochondrial and nuclear genomes on thermogenesis and building adaptation to the environment in mammals.

RevDate: 2018-07-01

Chakrabarty S, Kabekkodu SP, Singh RP, et al (2018)

Mitochondria in health and disease.

Mitochondrion pii:S1567-7249(18)30144-2 [Epub ahead of print].

Mitochondrial biology has become an area of intense research owing to the unique physiology of the organelle and its role in several types of cancers and other disorders. It has been found that mitochondria-encoded proteins, mitochondrial DNA and even RNA influence the functioning of the cell in more ways than were previously imagined. This may contribute to disease phenotypes which require detailed investigation and communication to the community health care providers. Additionally, this provides several novel avenues in drug designing against various cancers, neurodegenerative diseases and other metabolic disorders. The sixth annual conference of the Society for Mitochondrial Research and Medicine - India (SMRM) titled, 'Mitochondria in Health and Disease' was organized by Rana P. Singh at the School of Life Sciences, Jawaharlal Nehru University in New Delhi, India from 10th to 11th February 2017. The underlying objective of the conference was to provide a platform to discuss the recent advances in basic and translational research in mitochondrial biology and diseases. The conference aimed to translate academic research into clinical practice by providing a forum for basic researchers and clinicians to share their knowledge and build collaborations towards development of advanced therapeutic in mitochondrial diseases. To facilitate the knowledge-sharing, six major themes for the scientific sessions were (1) understanding of mitochondrial biology in disease progression, (2) advances in basic and translational mitochondrial research, (3) mitochondria in evolution and development, (4) targeting mitochondria for cancer prevention and treatment, (5) mitochondria in metabolic and neurological disorders and (6) mitochondria in stem cell and regeneration biology. This report summarizes the major outcomes of the discussions at the conference.

RevDate: 2018-10-16

Wang Q, Lu W, Yang J, et al (2018)

Comparative transcriptomics in three Passerida species provides insights into the evolution of avian mitochondrial complex I.

Comparative biochemistry and physiology. Part D, Genomics & proteomics, 28:27-36 pii:S1744-117X(18)30034-0 [Epub ahead of print].

Recent studies have shown that mitochondria play a crucial role in cellular energy production through the oxidative phosphorylation (OXPHOS) system. Complex I (NADH:ubiquinone oxidoreductase), the first and largest enzyme complex of the OXPHOS system, includes both nuclear- and mitochondrial-encoded proteins. However, the patterns of natural selection and phylogenetic implications of complex I in birds still remain unclear. In this study, we combined transcriptomic and phylogenetic analyses to comprehensively determine the evolution of avian complex I. The transcriptomes of three Passerida species (Leiothrix lutea, Spodiopsar sericeus, and Passer montanus) were obtained using the Illumina HiSeq™ 2500 system. More than 192,000,000 clean reads were assembled in a total of 828,267 transcripts. Evolutionary selection analysis suggested that six genes of the core subunits in avian complex I may have undergone putative positive selection. Notably, we found that the mean dN/dS (ω) ratio for mitochondrial genes of core subunits was significantly lower than that for nuclear genes of non-core subunits within complex I. The constructed maximum-parsimony, maximum-likelihood, and Bayesian inference phylogenetic trees were based on 44 complex I genes. We verified that the family Paridae (represented by Parus major and Pseudopodoces humilis) was clustered with Musicicapoidea. Our results provide new insights into the evolution of avian mitochondrial complex I.

RevDate: 2018-07-08

Lajbner Z, Pnini R, Camus MF, et al (2018)

Experimental evidence that thermal selection shapes mitochondrial genome evolution.

Scientific reports, 8(1):9500 pii:10.1038/s41598-018-27805-3.

Mitochondria are essential organelles, found within eukaryotic cells, which contain their own DNA. Mitochondrial DNA (mtDNA) has traditionally been used in population genetic and biogeographic studies as a maternally-inherited and evolutionary-neutral genetic marker. However, it is now clear that polymorphisms within the mtDNA sequence are routinely non-neutral, and furthermore several studies have suggested that such mtDNA polymorphisms are also sensitive to thermal selection. These observations led to the formulation of the "mitochondrial climatic adaptation" hypothesis, for which all published evidence to date is correlational. Here, we use laboratory-based experimental evolution in the fruit fly, Drosophila melanogaster, to test whether thermal selection can shift population frequencies of two mtDNA haplogroups whose natural frequencies exhibit clinal associations with latitude along the Australian east-coast. We present experimental evidence that the thermal regime in which the laboratory populations were maintained drove changes in haplogroup frequencies across generations. Our results strengthen the emerging view that intra-specific mtDNA variants are sensitive to selection, and suggest spatial distributions of mtDNA variants in natural populations of metazoans might reflect adaptation to climatic environments rather than within-population coalescence and diffusion of selectively-neutral haplotypes across populations.

RevDate: 2018-06-22

Vitali DG, Käser S, Kolb A, et al (2018)

Independent evolution of functionally exchangeable mitochondrial outer membrane import complexes.

eLife, 7: pii:34488.

Assembly and/or insertion of a subset of mitochondrial outer membrane (MOM) proteins, including subunits of the main MOM translocase, require the fungi-specific Mim1/Mim2 complex. So far it was unclear which proteins accomplish this task in other eukaryotes. Here, we show by reciprocal complementation that the MOM protein pATOM36 of trypanosomes is a functional analogue of yeast Mim1/Mim2 complex, even though these proteins show neither sequence nor topological similarity. Expression of pATOM36 rescues almost all growth, mitochondrial biogenesis, and morphology defects in yeast cells lacking Mim1 and/or Mim2. Conversely, co-expression of Mim1 and Mim2 restores the assembly and/or insertion defects of MOM proteins in trypanosomes ablated for pATOM36. Mim1/Mim2 and pATOM36 form native-like complexes when heterologously expressed, indicating that additional proteins are not part of these structures. Our findings indicate that Mim1/Mim2 and pATOM36 are the products of convergent evolution and arose only after the ancestors of fungi and trypanosomatids diverged.

RevDate: 2018-06-22

Tokatlidis K (2018)

Shaping the import system of mitochondria.

eLife, 7: pii:38209.

Evidence is accumulating that unrelated species have independently evolved the same way of importing proteins in their mitochondria.

RevDate: 2018-10-23
CmpDate: 2018-10-23

Seligmann H (2018)

Giant viruses as protein-coated amoeban mitochondria?.

Virus research, 253:77-86.

Mimivirus' genome includes parts of 5S, 16S and 23S ribosomal RNAs encoded by Acanthamoeba's mitogenome, the giant virus' host. Two non-exclusive hypotheses for rRNA remnants in giant viruses are examined: 1. mitogenomes invade viral genomes as they do for nuclear chromosomes (producing numts); 2. megaviral genomes evolved from an ancestral mitogenome. Alignment analyses confirm mitochondrial, rather than alphaproteobacterial origins of megaviral rRNAs. Other mitogenes have likely megaviral homologues. These megaviral homologues coevolve to much larger extents than candidate rRNA homologues, suggesting rRNA decay in viruses. Megaviral mitogene homologues overall follow mitochondrial gene order, suggesting mitogenome ancestry. Ancestral synteny decreases with megaviral genome size, suggesting that subsequent mitogene insertions blur ancestral gene order. Putative defenses against DNA invasion conserve mitogene order in short megaviral genomes. Synteny between mitogenome and megaviral genomes confirms the RNA/DNA polymerase-homologies-based hypothesis that giant viruses have mitochondrial-like ancestors, viral rRNA remnants are corollary of mitogenomic origins of megaviral genomes. Note that giant viruses, mitochondria and bacterial spores all have double membranes, spores and viruses have protein coats. Mitochondria might occasionally form spore-like structures that drifted into megaviruses. These missing links could confirm mitogenome ancestry of giant viruses rather than giant virus ancestry of mitochondria.

RevDate: 2018-08-13
CmpDate: 2018-08-13

Chadha S, Vijayan R, Gupta S, et al (2018)

Genetic manipulation of Leishmania donovani threonyl tRNA synthetase facilitates its exploration as a potential therapeutic target.

PLoS neglected tropical diseases, 12(6):e0006575 pii:PNTD-D-18-00530.

BACKGROUND: Aminoacyl tRNA synthetases are central enzymes required for protein synthesis. These enzymes are the known drug targets in bacteria and fungi. Here, we for the first time report the functional characterization of threonyl tRNA synthetase (LdThrRS) of Leishmania donovani, a protozoan parasite, the primary causative agent of visceral leishmaniasis.

METHODOLOGY: Recombinant LdThrRS (rLdThrRS) was expressed in E. coli and purified. The kinetic parameters for rLdThrRS were determined. The subcellular localization of LdThrRS was done by immunofluorescence analysis. Heterozygous mutants of LdThrRS were generated in Leishmania promastigotes. These genetically manipulated parasites were checked for their proliferation, virulence, aminoacylation activity and sensitivity to the known ThrRS inhibitor, borrelidin. An in silico generated structural model of L. donovani ThrRS was compared to that of human.

CONCLUSIONS: Recombinant LdThrRS displayed aminoacylation activity, and the protein is possibly localized to both the cytosol and mitochondria. The comparison of the 3D-model of LdThrRS to human ThrRS displayed considerable similarity. Heterozygous parasites showed restrictive growth phenotype and had attenuated infectivity. These heterozygous parasites were more susceptible to inhibition by borrelidin. Several attempts to obtain ThrRS homozygous null mutants were not successful, indicating its essentiality for the Leishmania parasite. Borrelidin showed a strong affinity for LdThrRS (KD: 0.04 μM) and was effective in inhibiting the aminoacylation activity of the rLdThrRS (IC50: 0.06 μM). Borrelidin inhibited the promastigotes (IC50: 21 μM) stage of parasites. Our data shows that LdThrRS is essential for L. donovani survival and is likely to bind with small drug-like molecules with strong affinity, thus making it a potential target for drug discovery efforts.

RevDate: 2018-10-15
CmpDate: 2018-10-15

Hein A, V Knoop (2018)

Expected and unexpected evolution of plant RNA editing factors CLB19, CRR28 and RARE1: retention of CLB19 despite a phylogenetically deep loss of its two known editing targets in Poaceae.

BMC evolutionary biology, 18(1):85 pii:10.1186/s12862-018-1203-4.

BACKGROUND: C-to-U RNA editing in mitochondria and chloroplasts and the nuclear-encoded, RNA-binding PPR proteins acting as editing factors present a wide field of co-evolution between the different genetic systems in a plant cell. Recent studies on chloroplast editing factors RARE1 and CRR28 addressing one or two chloroplast editing sites, respectively, found them strictly conserved among 65 flowering plants as long as one of their RNA editing targets remained present.

RESULTS: Extending the earlier sampling to 117 angiosperms with high-quality genome or transcriptome data, we find more evidence confirming previous conclusions but now also identify cases for expected evolutionary transition states such as retention of RARE1 despite loss of its editing target or the degeneration of CRR28 truncating its carboxyterminal DYW domain. The extended angiosperm set was now used to explore CLB19, an "E+"-type PPR editing factor targeting two chloroplast editing sites, rpoAeU200SF and clpPeU559HY, in Arabidopsis thaliana. We found CLB19 consistently conserved if one of the two targets was retained and three independent losses of CLB19 after elimination of both targets. The Ericales show independent regains of the ancestrally lost clpPeU559HY editing, further explaining why multiple-target editing factors are lost much more rarely than single target factors like RARE1. The retention of CLB19 despite loss of both editing targets in some Ericaceae, Apocynaceae and in Camptotheca (Nyssaceae) likely represents evolutionary transitions. However, the retention of CLB19 after a phylogenetic deep loss in the Poaceae rather suggests a yet unrecognized further editing target, for which we suggest editing event ndhAeU473SL.

CONCLUSION: Extending the scope of studies on plant organelle RNA editing to further taxa and additional nuclear cofactors reveals expected evolutionary transitions, strikingly different evolutionary dynamics for multiple-target editing factors like CLB19 and CRR28 and suggests additional functions for editing factor CLB19 among the Poaceae.

RevDate: 2018-09-26
CmpDate: 2018-09-26

Bonsack F, S Sukumari-Ramesh (2018)

TSPO: An Evolutionarily Conserved Protein with Elusive Functions.

International journal of molecular sciences, 19(6): pii:ijms19061694.

TSPO (18 kDa translocator protein) was identified decades ago in a search for peripheral tissue binding sites for benzodiazepines, and was formerly called the peripheral benzodiazepine receptor. TSPO is a conserved protein throughout evolution and it is implicated in the regulation of many cellular processes, including inflammatory responses, oxidative stress, and mitochondrial homeostasis. TSPO, apart from its broad expression in peripheral tissues, is highly expressed in neuroinflammatory cells, such as activated microglia. In addition, emerging studies employing the ligands of TSPO suggest that TSPO plays an important role in neuropathological settings as a biomarker and therapeutic target. However, the precise molecular function of this protein in normal physiology and neuropathology remains enigmatic. This review provides an overview of recent advances in our understanding of this multifaceted molecule and identifies the knowledge gap in the field for future functional studies.

RevDate: 2018-09-21

Scott GR, Guo KH, NJ Dawson (2018)

The Mitochondrial Basis for Adaptive Variation in Aerobic Performance in High-Altitude Deer Mice.

Integrative and comparative biology, 58(3):506-518.

Mitochondria play a central role in aerobic performance. Studies aimed at elucidating how evolved variation in mitochondrial physiology contributes to adaptive variation in aerobic performance can therefore provide a unique and powerful lens to understanding the evolution of complex physiological traits. Here, we review our ongoing work on the importance of changes in mitochondrial quantity and quality to adaptive variation in aerobic performance in high-altitude deer mice. Whole-organism aerobic capacity in hypoxia (VO2max) increases in response to hypoxia acclimation in this species, but high-altitude populations have evolved consistently greater VO2max than populations from low altitude. The evolved increase in VO2max in highlanders is associated with an evolved increase in the respiratory capacity of the gastrocnemius muscle. This appears to result from highlanders having more mitochondria in this tissue, attributed to a higher proportional abundance of oxidative fiber-types and a greater mitochondrial volume density within oxidative fibers. The latter is primarily caused by an over-abundance of subsarcolemmal mitochondria in high-altitude mice, which is likely advantageous for mitochondrial O2 supply because more mitochondria are situated adjacent to the cell membrane and close to capillaries. Evolved changes in gastrocnemius phenotype appear to be underpinned by population differences in the expression of genes involved in energy metabolism, muscle development, and vascular development. Hypoxia acclimation has relatively little effect on respiratory capacity of the gastrocnemius, but it increases respiratory capacity of the diaphragm. However, the mechanisms responsible for this increase differ between populations: lowlanders appear to adjust mitochondrial quantity and quality (i.e., increases in citrate synthase [CS] activity, and mitochondrial respiration relative to CS activity) and they exhibit higher rates of mitochondrial release of reactive oxygen species, whereas highlanders only increase mitochondrial quantity in response to hypoxia acclimation. In contrast to the variation in skeletal muscles, the respiratory capacity of cardiac muscle does not appear to be affected by hypoxia acclimation and varies little between populations. Therefore, evolved changes in mitochondrial quantity and quality make important tissue-specific contributions to adaptive variation in aerobic performance in high-altitude deer mice.

RevDate: 2018-10-04
CmpDate: 2018-10-02

Avelange-Macherel MH, Candat A, Neveu M, et al (2018)

Decoding the Divergent Subcellular Location of Two Highly Similar Paralogous LEA Proteins.

International journal of molecular sciences, 19(6): pii:ijms19061620.

Many mitochondrial proteins are synthesized as precursors in the cytosol with an N-terminal mitochondrial targeting sequence (MTS) which is cleaved off upon import. Although much is known about import mechanisms and MTS structural features, the variability of MTS still hampers robust sub-cellular software predictions. Here, we took advantage of two paralogous late embryogenesis abundant proteins (LEA) from Arabidopsis with different subcellular locations to investigate structural determinants of mitochondrial import and gain insight into the evolution of the LEA genes. LEA38 and LEA2 are short proteins of the LEA_3 family, which are very similar along their whole sequence, but LEA38 is targeted to mitochondria while LEA2 is cytosolic. Differences in the N-terminal protein sequences were used to generate a series of mutated LEA2 which were expressed as GFP-fusion proteins in leaf protoplasts. By combining three types of mutation (substitution, charge inversion, and segment replacement), we were able to redirect the mutated LEA2 to mitochondria. Analysis of the effect of the mutations and determination of the LEA38 MTS cleavage site highlighted important structural features within and beyond the MTS. Overall, these results provide an explanation for the likely loss of mitochondrial location after duplication of the ancestral gene.

RevDate: 2018-06-22
CmpDate: 2018-06-22

Wang M, Y Teng (2018)

Genome-wide identification and analysis of MICU genes in land plants and their potential role in calcium stress.

Gene, 670:174-181.

Mitochondrial calcium uptake (MICU) plays a vital role in the regulation of mitochondrial calcium homeostasis, and, consequently, influences calcium signaling transduction. Although genes involved in mitochondrial calcium uptake have been well studied in animals, less is known about their ubiquity and function in plants. In this study, we identified 96 MICU genes in land plants. On the basis of phylogenetic analysis of MICU proteins, they were classified into three clades: MICU from eudicots (Clade I), from monocots (Clade II), and from a basal angiosperm, a bryophyte, and a lycophyte (Clade III). Pairwise identity analysis across all MICU proteins showed that they are highly conserved among land plants at the protein level. Conserved motif analysis showed that most MICU proteins contained three EF-hands, and an additional EF-hand motif first identified in the MICU of Arabidopsis thaliana but not mammals was found in all 96 putative MICU proteins. This suggests that a cellular pathway of calcium uptake and signaling that requires three EF-hand motifs is evolutionarily conserved in plants. In addition, we discovered that MICU-defective mutants of Arabidopsis thaliana exhibited longer roots than wild-type under high calcium stress. Concurrently, the mRNA transcription levels of MICU were decreased under high calcium conditions. These results suggest that loss-of-function mutations of MICU may have potential roles in helping plants resist high calcium stress. This study provides clues to the possible role of plant MICU in mitochondrial calcium uptake, as well as useful information to support further studies on MICU function in plants.

RevDate: 2018-10-22
CmpDate: 2018-10-22

Solari KA, EA Hadly (2018)

Evolution for extreme living: variation in mitochondrial cytochrome c oxidase genes correlated with elevation in pikas (genus Ochotona).

Integrative zoology, 13(5):517-535.

The genus Ochotona (pikas) is a clade of cold-tolerant lagomorphs that includes many high-elevation species. Pikas offer a unique opportunity to study adaptations and potential limitations of an ecologically important mammal to high-elevation hypoxia. We analyzed the evolution of 3 mitochondrial genes encoding the catalytic core of cytochrome c oxidase (COX) in 10 pika species occupying elevations from sea level to 5000 m. COX is an enzyme highly reliant on oxygen and essential for cell function. One amino acid property, the equilibrium constant (ionization of COOH), was found to be under selection in the overall protein complex. We observed a strong relationship between the net value change in this property and the elevation each species occupies, with higher-elevation species having potentially more efficient proteins. We also found evidence of selection in low-elevation species for potentially less efficient COX, perhaps trading efficiency for heat production in the absence of hypoxia. Our results suggest that different pika species may have evolved elevation-specific COX proteins, specialization that may indicate limitations in their ability to shift their elevational ranges in response to future climate change.

RevDate: 2018-10-15
CmpDate: 2018-10-15

Bronstein O, Kroh A, E Haring (2018)

Mind the gap! The mitochondrial control region and its power as a phylogenetic marker in echinoids.

BMC evolutionary biology, 18(1):80 pii:10.1186/s12862-018-1198-x.

BACKGROUND: In Metazoa, mitochondrial markers are the most commonly used targets for inferring species-level molecular phylogenies due to their extremely low rate of recombination, maternal inheritance, ease of use and fast substitution rate in comparison to nuclear DNA. The mitochondrial control region (CR) is the main non-coding area of the mitochondrial genome and contains the mitochondrial origin of replication and transcription. While sequences of the cytochrome oxidase subunit 1 (COI) and 16S rRNA genes are the prime mitochondrial markers in phylogenetic studies, the highly variable CR is typically ignored and not targeted in such analyses. However, the higher substitution rate of the CR can be harnessed to infer the phylogeny of closely related species, and the use of a non-coding region alleviates biases resulting from both directional and purifying selection. Additionally, complete mitochondrial genome assemblies utilizing next generation sequencing (NGS) data often show exceptionally low coverage at specific regions, including the CR. This can only be resolved by targeted sequencing of this region.

RESULTS: Here we provide novel sequence data for the echinoid mitochondrial control region in over 40 species across the echinoid phylogenetic tree. We demonstrate the advantages of directly targeting the CR and adjacent tRNAs to facilitate complementing low coverage NGS data from complete mitochondrial genome assemblies. Finally, we test the performance of this region as a phylogenetic marker both in the lab and in phylogenetic analyses, and demonstrate its superior performance over the other available mitochondrial markers in echinoids.

CONCLUSIONS: Our target region of the mitochondrial CR (1) facilitates the first thorough investigation of this region across a wide range of echinoid taxa, (2) provides a tool for complementing missing data in NGS experiments, and (3) identifies the CR as a powerful, novel marker for phylogenetic inference in echinoids due to its high variability, lack of selection, and high compatibility across the entire class, outperforming conventional mitochondrial markers.

RevDate: 2018-09-28

Darbani B, Kell DB, I Borodina (2018)

Energetic evolution of cellular Transportomes.

BMC genomics, 19(1):418 pii:10.1186/s12864-018-4816-5.

BACKGROUND: Transporter proteins mediate the translocation of substances across the membranes of living cells. Many transport processes are energetically expensive and the cells use 20 to 60% of their energy to power the transportomes. We hypothesized that there may be an evolutionary selection pressure for lower energy transporters.

RESULTS: We performed a genome-wide analysis of the compositional reshaping of the transportomes across the kingdoms of bacteria, archaea, and eukarya. We found that the share of ABC transporters is much higher in bacteria and archaea (ca. 27% of the transportome) than in primitive eukaryotes (13%), algae and plants (10%) and in fungi and animals (5-6%). This decrease is compensated by an increased occurrence of secondary transporters and ion channels. The share of ion channels is particularly high in animals (ca. 30% of the transportome) and algae and plants with (ca. 13%), when compared to bacteria and archaea with only 6-7%. Therefore, our results show a move to a preference for the low-energy-demanding transporters (ion channels and carriers) over the more energy-costly transporter classes (ATP-dependent families, and ABCs in particular) as part of the transition from prokaryotes to eukaryotes. The transportome analysis also indicated seven bacterial species, including Neorickettsia risticii and Neorickettsia sennetsu, as likely origins of the mitochondrion in eukaryotes, based on the phylogenetically restricted presence therein of clear homologues of modern mitochondrial solute carriers.

CONCLUSIONS: The results indicate that the transportomes of eukaryotes evolved strongly towards a higher energetic efficiency, as ATP-dependent transporters diminished and secondary transporters and ion channels proliferated. These changes have likely been important in the development of tissues performing energetically costly cellular functions.

RevDate: 2018-06-01

Hartmann T, Bernt M, M Middendorf (2018)

EqualTDRL: illustrating equivalent tandem duplication random loss rearrangements.

BMC bioinformatics, 19(1):192 pii:10.1186/s12859-018-2170-x.

BACKGROUND: To study the differences between two unichromosomal circular genomes, e.g., mitochondrial genomes, under the tandem duplication random loss (TDRL) rearrangement it is important to consider the whole set of potential TDRL rearrangement events that could have taken place. The reason is that for two given circular gene orders there can exist different TDRL rearrangements that transform one of the gene orders into the other. Hence, a TDRL event cannot always be reconstructed only from the knowledge of the circular gene order before a TDRL event and the circular gene order after it.

RESULTS: We present the program EqualTDRL that computes and illustrates the complete set of TDRLs for pairs of circular gene orders that differ by only one TDRL. EqualTDRL considers the circularity of the given genomes and certain restrictions on the TDRL rearrangements. Examples for the latter are sequences of genes that have to be conserved during a TDRL or pairs of genes that frame intergenic regions which might represent remnants of duplicated genes. Additionally, EqualTDRL allows to determine the set of TDRLs that are minimum with respect to the number of duplicated genes.

CONCLUSION: EqualTDRL supports scientists to study the complete set of TDRLs that possibly could have taken place in the evolution of mitochondrial genomes. EqualTDRL is implemented in C++ using the ggplot2 package of the open source programming language R and is freely available from http://pacosy.informatik.uni-leipzig.de/equaltdrl .

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ESP Quick Facts

ESP Origins

In the early 1990's, Robert Robbins was a faculty member at Johns Hopkins, where he directed the informatics core of GDB — the human gene-mapping database of the international human genome project. To share papers with colleagues around the world, he set up a small paper-sharing section on his personal web page. This small project evolved into The Electronic Scholarly Publishing Project.

ESP Support

In 1995, Robbins became the VP/IT of the Fred Hutchinson Cancer Research Center in Seattle, WA. Soon after arriving in Seattle, Robbins secured funding, through the ELSI component of the US Human Genome Project, to create the original ESP.ORG web site, with the formal goal of providing free, world-wide access to the literature of classical genetics.

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Although the methods of molecular biology can seem almost magical to the uninitiated, the original techniques of classical genetics are readily appreciated by one and all: cross individuals that differ in some inherited trait, collect all of the progeny, score their attributes, and propose mechanisms to explain the patterns of inheritance observed.

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In reading the early works of classical genetics, one is drawn, almost inexorably, into ever more complex models, until molecular explanations begin to seem both necessary and natural. At that point, the tools for understanding genome research are at hand. Assisting readers reach this point was the original goal of The Electronic Scholarly Publishing Project.

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Usage of the site grew rapidly and has remained high. Faculty began to use the site for their assigned readings. Other on-line publishers, ranging from The New York Times to Nature referenced ESP materials in their own publications. Nobel laureates (e.g., Joshua Lederberg) regularly used the site and even wrote to suggest changes and improvements.

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When the site began, no journals were making their early content available in digital format. As a result, ESP was obliged to digitize classic literature before it could be made available. For many important papers — such as Mendel's original paper or the first genetic map — ESP had to produce entirely new typeset versions of the works, if they were to be available in a high-quality format.

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Early support from the DOE component of the Human Genome Project was critically important for getting the ESP project on a firm foundation. Since that funding ended (nearly 20 years ago), the project has been operated as a purely volunteer effort. Anyone wishing to assist in these efforts should send an email to Robbins.

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