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Bibliography on: Mitochondrial Evolution

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ESP: PubMed Auto Bibliography 20 Jul 2019 at 01:44 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 26799652[PMID] NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)

RevDate: 2019-07-18

Rubalcava-Gracia D, García-Rincón J, Pérez-Montfort R, et al (2019)

Key within-membrane residues and precursor dosage impact the allotopic expression of yeast subunit II of cytochrome c oxidase.

Molecular biology of the cell [Epub ahead of print].

Experimentally relocating mitochondrial genes to the nucleus for functional expression (allotopic expression) is a challenging process. The high hydrophobicity of mitochondria-encoded proteins seems to be one of the main factors preventing this allotopic expression. We focused on subunit II of cytochrome c oxidase (Cox2) to study which modifications may enable or improve its allotopic expression in yeast. Cox2 can be imported from the cytosol into mitochondria in the presence of the W56R substitution, which decreases the protein hydrophobicity and allows partial respiratory rescue of a cox2-null strain. We show that the inclusion of a positive charge is more favorable over substitutions that only decrease the hydrophobicity. We also searched for other determinants enabling allotopic expression in yeast by examining the COX2 gene in organisms where it was transferred to the nucleus during evolution. We found that naturally occurring variations at within-membrane residues in the legume Glycine max Cox2 could enable yeast COX2 allotopic expression. We also evidence that directing high doses of allotopically-synthesized Cox2 to mitochondria seems to be counterproductive because the subunit aggregates at the mitochondrial surface. Our findings are relevant for the design of allotopic expression strategies and contribute to the understanding of gene retention in organellar genomes.

RevDate: 2019-07-17
CmpDate: 2019-07-17

Gavish M, L Veenman (2018)

Regulation of Mitochondrial, Cellular, and Organismal Functions by TSPO.

Advances in pharmacology (San Diego, Calif.), 82:103-136.

In 1999, the enigma of the 18kDa mitochondrial translocator protein (TSPO), also known as the peripheral-type benzodiazepine receptor, was the seeming disparity of the many functions attributed to TSPO, ranging from the potential of TSPO acting as a housekeeping gene at molecular biological levels to adaptations to stress, and even involvement in higher emotional and cognitive functioning, such as anxiety and depression. In the years since then, knowledge regarding the many functions modulated by TSPO has expanded, and understanding has deepened. In addition, new functions could be firmly associated with TSPO, such as regulation of programmed cell death and modulation of gene expression. Interestingly, control by the mitochondrial TSPO over both of these life and death functions appears to include Ca++ homeostasis, generation of reactive oxygen species (ROS), and ATP production. Other mitochondrial functions under TSPO control are considered to be steroidogenesis and tetrapyrrole metabolism. As TSPO effects on gene expression and on programmed cell death can be related to the wide range of functions that can be associated with TSPO, several of these five elements of Ca++, ROS, ATP, steroids, and tetrapyrroles may indeed form the basis of TSPO's capability to operate as a multifunctional housekeeping gene to maintain homeostasis of the cell and of the whole multicellular organism.

RevDate: 2019-07-15
CmpDate: 2019-07-15

Isaac RS, McShane E, LS Churchman (2018)

The Multiple Levels of Mitonuclear Coregulation.

Annual review of genetics, 52:511-533.

Together, the nuclear and mitochondrial genomes encode the oxidative phosphorylation (OXPHOS) complexes that reside in the mitochondrial inner membrane and enable aerobic life. Mitochondria maintain their own genome that is expressed and regulated by factors distinct from their nuclear counterparts. For optimal function, the cell must ensure proper stoichiometric production of OXPHOS subunits by coordinating two physically separated and evolutionarily distinct gene expression systems. Here, we review our current understanding of mitonuclear coregulation primarily at the levels of transcription and translation. Additionally, we discuss other levels of coregulation that may exist but remain largely unexplored, including mRNA modification and stability and posttranslational protein degradation.

RevDate: 2019-07-11
CmpDate: 2019-07-11

Wang J, Zhou YA, Su LP, et al (2019)

[Instability of Mitochondrial DNA D-loop Region Genes in Patients with Leukemia].

Zhongguo shi yan xue ye xue za zhi, 27(3):657-663.

OBJECTIVE: To study the instability of mitochondrial DNA(mt DNA) D-loop region genes in patients with Leukemia.

METHODS: The HV-1 and HV-2 regions of D-loop region in 24 patients with leukemia were amplificated and sequenced, then their results were compared with revised Cambridge reference sequence (rCRS) and Databank mtDB. The mutation rate was detected by SPSS 22.0 statistics software.

RESULTS: The total mutation rate in patients was 95.83% (23/24), the detection showed 82 mutated genes, out of which 47 (57.32%) mutated genes located in HV-1 region, 35 (42.68%) mutated genes in HV-2 region. The comparison showed that the mutation rate in untreated (UT) group and treated (T) group of AML patients was (2.37±0.82)×10-3 and (4.76±2.45)×10-3 respectively(P<0.01), the mutation rate in PR and CR groups of treated AML patients was (5.10±2.56)×10-3 and (4.51±2.51)×10-3 respectively (P<0.05), the comparison among M3 group showed that the mutation rates in UT, PR and CR groups were (2.55±0.63)×10-3, (5.37±3.41)×10-3 and (3.71±1.65)×10-3 respectively (P>0.05).

CONCLUSION: The more high mutation rate and many kinds of mutation types exist in D-loop region, suggesting that the genes in D-loop region display the more strong instability, the chemotherapy may aggravate the instability of genes in D-loop region.

RevDate: 2019-07-10

Brian JI, Davy SK, SP Wilkinson (2019)

Multi-gene incongruence consistent with hybridisation in Cladocopium (Symbiodiniaceae), an ecologically important genus of coral reef symbionts.

PeerJ, 7:e7178 pii:7178.

Coral reefs rely on their intracellular dinoflagellate symbionts (family Symbiodiniaceae) for nutritional provision in nutrient-poor waters, yet this association is threatened by thermally stressful conditions. Despite this, the evolutionary potential of these symbionts remains poorly characterised. In this study, we tested the potential for divergent Symbiodiniaceae types to sexually reproduce (i.e. hybridise) within Cladocopium, the most ecologically prevalent genus in this family. With sequence data from three organelles (cob gene, mitochondrion; psbAncr region, chloroplast; and ITS2 region, nucleus), we utilised the Incongruence Length Difference test, Approximately Unbiased test, tree hybridisation analyses and visual inspection of raw data in stepwise fashion to highlight incongruences between organelles, and thus provide evidence of reticulate evolution. Using this approach, we identified three putative hybrid Cladocopium samples among the 158 analysed, at two of the seven sites sampled. These samples were identified as the common Cladocopium types C40 or C1 with respect to the mitochondria and chloroplasts, but the rarer types C3z, C3u and C1# with respect to their nuclear identity. These five Cladocopium types have previously been confirmed as evolutionarily distinct and were also recovered in non-incongruent samples multiple times, which is strongly suggestive that they sexually reproduced to produce the incongruent samples. A concomitant inspection of next generation sequencing data for these samples suggests that other plausible explanations, such as incomplete lineage sorting or the presence of co-dominance, are much less likely. The approach taken in this study allows incongruences between gene regions to be identified with confidence, and brings new light to the evolutionary potential within Symbiodiniaceae.

RevDate: 2019-07-08

Forsythe ES, Sharbrough J, Havird JC, et al (2019)

CyMIRA: The Cytonuclear Molecular Interactions Reference for Arabidopsis.

Genome biology and evolution pii:5529674 [Epub ahead of print].

The function and evolution of eukaryotic cells depends upon direct molecular interactions between gene products encoded in nuclear and cytoplasmic genomes. Understanding how these cytonuclear interactions drive molecular evolution and generate genetic incompatibilities between isolated populations and species is of central importance to eukaryotic biology. Plants are an outstanding system to investigate such effects because of their two different genomic compartments present in the cytoplasm (mitochondria and plastids) and the extensive resources detailing subcellular targeting of nuclear-encoded proteins. However, the field lacks a consistent classification scheme for mitochondrial- and plastid-targeted proteins based on their molecular interactions with cytoplasmic genomes and gene products, which hinders efforts to standardize and compare results across studies. Here, we take advantage of detailed knowledge about the model angiosperm Arabidopsis thaliana to provide a curated database of plant cytonuclear interactions at the molecular level. CyMIRA (Cytonuclear Molecular Interactions Reference for Arabidopsis) is available at http://cymira.colostate.edu/ and https://github.com/dbsloan/cymira and will serve as a resource to aid researchers in partitioning evolutionary genomic data into functional gene classes based on organelle targeting and direct molecular interaction with cytoplasmic genomes and gene products. It includes 11 categories (and 27 subcategories) of different cytonuclear complexes and types of molecular interactions, and it reports residue-level information for cytonuclear contact sites. We hope that this framework will make it easier to standardize, interpret and compare studies testing the functional and evolutionary consequences of cytonuclear interactions.

RevDate: 2019-07-08

McKenzie JL, Chung DJ, Healy TM, et al (2019)

Mitochondrial ecophysiology: assessing the evolutionary forces that shape mitochondrial variation.

Integrative and comparative biology pii:5529679 [Epub ahead of print].

The mitonuclear species concept hypothesizes that incompatibilities between interacting gene products of the nuclear and mitochondrial genomes are a major factor establishing and maintaining species boundaries. However, most of the data available to test this concept come from studies of genetic variation in mitochondrial DNA, and clines in the mitochondrial genome across contact zones can be produced by a variety of forces. Here, we show that using a combination of population genomic analyses of the nuclear and mitochondrial genomes and studies of mitochondrial function can provide insight into the relative roles of neutral processes, adaptive evolution, and mitonuclear incompatibility in establishing and maintaining mitochondrial clines, using Atlantic killifish (Fundulus heteroclitus) as a case study. There is strong evidence for a role of secondary contact following the last glaciation in shaping a steep mitochondrial cline across a contact zone between northern and southern subspecies of killifish, but there is also evidence for a role of adaptive evolution in driving differentiation between the subspecies in a variety of traits from the level of the whole organism to the level of mitochondrial function. In addition, studies are beginning to address the potential for mitonuclear incompatibilities in admixed populations. However, population genomic studies have failed to detect evidence for a strong and pervasive influence of mitonuclear incompatibilities, and we suggest that polygenic selection may be responsible for the complex patterns observed. This case study demonstrates that multiple forces can act together in shaping mitochondrial clines, and illustrates the challenge of disentangling their relative roles.

RevDate: 2019-07-08
CmpDate: 2019-07-08

Saikia M, Nath R, D Devi (2019)

Genetic diversity and phylogeny analysis of Antheraea assamensis Helfer (Lepidoptera: Saturniidae) based on mitochondrial DNA sequences.

Journal of genetics, 98(1):.

Antheraea assamensis Helfer, popularly known as Muga silkworm, the golden silk producer of northeast India is economically important and unique among the Saturniid silkworms. In this study, the genetic diversity and phylogeny of semidomesticated and wild morphs of Muga silkwormcollected from different geographical locations of northeast India were investigated based on the sequences of five mitochondrial loci, i.e. 12S rRNA, 16S rRNA, CoxI, Cytb and CR. All the five mitochondrial loci showed a strong bias towards higher 'A' and 'T' contents. Transitional substitutions were found to be more than the transversional substitutions. The rate of nucleotide substitution and average genetic divergence were found to be highest in CR sequences and lowest in 12S rRNA gene sequences among the morphs of Muga silkworm. The morphs collected from same geographical area had identical 12S rRNA, 16S rRNA, CoxI and Cytb gene sequences. Moreover, the 12S rRNA and 16S rRNA gene sequences of somesemi-domesticated and wild morphs collected from different geographical locations were also found to be similar. In the phylogenetic trees generated based on themitochondrial loci, mixing of semi-domesticated and wild morphs was observed as they shared the same group. The information generated in this study will help in formulating strategies to conserve the natural biodiversity present among these unique silkworms in northeast India. In addition, this will be useful in identifying diverse morphs of Muga silkworm, which will help in effective breeding programmes to improve its productivity.

RevDate: 2019-07-08
CmpDate: 2019-07-08

Purushothaman P, Chakraborty RD, Kuberan G, et al (2019)

Integrative taxonomy of commercially important deep water penaeoid shrimps from India.

Journal of genetics, 98(1):.

The deep water penaeoid shrimp is an important commercial crustacean resource along the Indian coast. The molecular and morphological information of this group from the Indian coast is scarcely known. In this study, we investigated the identification and phylogenetic relationships of the deep water penaeoid shrimps using three mitochondrial (cytochrome oxidase subunit I (COI), cytochrome b, 16S rRNA) genes, which were compared with 54 morphological characters and further used to evaluate character evolution. Our study revealed remarkable molecular divergence (3.3-33.0%) in nine species from three genera of Solenoceridae, four species from three genera of Penaeidae and one species from Aristeidae using COI. Phylogenetic analysis using maximum likelihood and Bayesian approaches revealed that all species from these families are monophyletic. The present analysis revealed the existence of subgroups in the genus Solenocera suggesting the slow reduction of postrostral carina which corresponds to the increase in distributional depth during the evolutionary process which further indicates the origin of the genus in the continental shelf and extending up to the continental slope. In addition, we generated the DNA barcode database involving these species which can help further to investigate the detailed evolution and biogeography of these valuable crustacean resources.

RevDate: 2019-07-08
CmpDate: 2019-07-08

Brenner WG, Mader M, Müller NA, et al (2019)

High Level of Conservation of Mitochondrial RNA Editing Sites Among Four Populus Species.

G3 (Bethesda, Md.), 9(3):709-717 pii:g3.118.200763.

RNA editing occurs in the endosymbiont organelles of higher plants as C-to-U conversions of defined nucleotides. The availability of large quantities of RNA sequencing data makes it possible to identify RNA editing sites and to quantify their editing extent. We have investigated RNA editing in 34 protein-coding mitochondrial transcripts of four Populus species, a genus noteworthy for its remarkably small number of RNA editing sites compared to other angiosperms. 27 of these transcripts were subject to RNA editing in at least one species. In total, 355 RNA editing sites were identified with high confidence, their editing extents ranging from 10 to 100%. The most heavily edited transcripts were ccmB with the highest density of RNA editing sites (53.7 sites / kb) and ccmFn with the highest number of sites (39 sites). Most of the editing events are at position 1 or 2 of the codons, usually altering the encoded amino acid, and are highly conserved among the species, also with regard to their editing extent. However, one SNP was found in the newly sequenced and annotated mitochondrial genome of P. alba resulting in the loss of an RNA editing site compared to P. tremula and P. davidiana This SNP causes a C-to-T transition and an amino acid exchange from Ser to Phe, highlighting the widely discussed role of RNA editing in compensating mutations.

RevDate: 2019-07-05
CmpDate: 2019-07-05

Banerjee B, Koner D, Bhuyan G, et al (2018)

Differential expression of multiple glutamine synthetase genes in air-breathing magur catfish, Clarias magur and their induction under hyper-ammonia stress.

Gene, 671:85-95.

The present study demonstrates the unique presence of three different gs genes (cmgs01, cmgs02, and cmgs03) in air-breathing ureogenic magur catfish (Clarias magur), which is otherwise reported to be encoded by a single gene in higher vertebrates. Of these three genes, two (cmgs01and cmgs03) were identified as 'liver' form, predominantly expressed in liver cells, and the third one as 'brain' form (cmgs02), expressed chiefly in brain cells. Molecular characterization studies have revealed conservation of homologous active site residues in all the three gs genes. In silico analysis, accompanied by GS enzyme assay and Western blot analysis of different GS isoforms in different subcellular fractions indicated the mitochondrial localization of cmGS01 and cmGS03 in liver and kidney cells and cytosolic localization of cmGS02 in brain cells. Further, exposure of magur catfish to high external ammonia (HEA; 25 mM NH4Cl) led to a significant induction of multiple gs genes as evidenced by higher expression of different gs mRNAs at variable levels in different tissues. The cmgs01 and cmgs03 mRNA levels elevated significantly in liver, kidney, muscle, and gills, whereas the cmgs02 mRNA level increased considerably in the brain after 14 days of exposure to HEA. These increases in mRNA levels were associated with a significant rise in cmGS01 and cmGS03 proteins in liver, kidney, muscle, and gills, and the cmGS02 protein in the brain after 14 days of exposure to HEA. Therefore, it can be concluded that the unique differential expression of three gs genes and their induction under high ammonia level probably helps in detoxification of ammonia to glutamine and further to urea via the ornithine-urea cycle in ureogenic as well as non-ureogenic tissues of these magur catfish.

RevDate: 2019-07-03
CmpDate: 2019-07-03

Mafra ACP, SMG Dias (2019)

Several Faces of Glutaminase Regulation in Cells.

Cancer research, 79(7):1302-1304.

The cancer target glutaminase (GLS) has proven to be a fascinating protein. Since it was first described to be regulated by the oncogene Myc 10 years ago, several other transcriptional, posttranscriptional, and posttranslational regulatory mechanisms have emerged, and the list is growing. A recent study by Deng and colleagues revealed that an antisense (AS) long noncoding RNA named GLS-AS, which is negatively regulated by Myc, downregulates GLS in pancreatic cancer. The Myc/GLS-AS/GLS regulatory axis is activated by nutrient stress, which is important for the often hypovascular pancreatic cancer, displaying the significance of GLS for the progression of this highly lethal type of cancer.See related article by Deng et al., p. 1398.

RevDate: 2019-07-03
CmpDate: 2019-07-03

Kolli R, Soll J, C Carrie (2019)

OXA2b is Crucial for Proper Membrane Insertion of COX2 during Biogenesis of Complex IV in Plant Mitochondria.

Plant physiology, 179(2):601-615.

The evolutionarily conserved YidC/Oxa1/Alb3 proteins are involved in the insertion of membrane proteins in all domains of life. In plant mitochondria, individual knockouts of OXA1a, OXA2a, and OXA2b are embryo-lethal. In contrast to other members of the protein family, OXA2a and OXA2b contain a tetratricopeptide repeat (TPR) domain at the C-terminus. Here, the role of Arabidopsis (Arabidopsis thaliana) OXA2b was determined by using viable mutant plants that were generated by complementing homozygous lethal OXA2b T-DNA insertional mutants with a C-terminally truncated OXA2b lacking the TPR domain. The truncated-OXA2b-complemented plants displayed severe growth retardation due to a strong reduction in the steady-state abundance and enzyme activity of the mitochondrial respiratory chain complex IV. The TPR domain of OXA2b directly interacts with cytochrome c oxidase subunit 2, aiding in efficient membrane insertion and translocation of its C-terminus. Thus, OXA2b is crucial for the biogenesis of complex IV in plant mitochondria.

RevDate: 2019-07-03
CmpDate: 2019-07-03

Makiuchi T, Santos HJ, Tachibana H, et al (2017)

Hetero-oligomer of dynamin-related proteins participates in the fission of highly divergent mitochondria from Entamoeba histolytica.

Scientific reports, 7(1):13439.

Entamoeba histolytica is an anaerobic parasitic protist and possesses mitosomes, one of the most highly divergent mitochondrion-related organelles (MROs). Although unique metabolism and protein/metabolite transport machinery have been demonstrated in Entamoeba mitosomes, the mechanism of mitosomal fusion and fission remains to be elucidated. In this study, we demonstrate that two dynamin-related proteins (DRPs) are cooperatively involved in the fission of Entamoeba mitosomes. Expression of a dominant negative form of EhDrpA and EhDrpB, and alternatively, repression of gene expression of EhDrpA and EhDrpB genes, caused elongation of mitosomes, reflecting inhibition of mitosomal fission. Moreover, EhDrpA and EhDrpB formed an unprecedented hetero-oligomeric complex with an approximate 1:2 to 1:3 ratio, suggesting that the observed elongation of mitosomes is likely caused by the disruption and instability of the complex caused by an imbalance in the two DRPs. Altogether, this is the first report of a hetero-oligomeric DRP complex which participates in the fission of mitochondria and MROs.

RevDate: 2019-07-01
CmpDate: 2019-07-01

Xie T, Hu L, Guo YX, et al (2019)

Genetic polymorphism analysis of mitochondrial DNA from Chinese Xinjiang Kazak ethnic group by a novel mitochondrial DNA genotyping panel.

Molecular biology reports, 46(1):17-25.

Genetic polymorphism analysis of 60 mitochondrial DNA (mtDNA) loci in Chinese Xinjiang Kazak group was conducted in this study. Blood samples from 141 unrelated healthy volunteers were randomly collected from Chinese Kazak ethnic group in Ili, Xinjiang Uygur Autonomous region. Among these mtDNA loci, single nucleotide transition was the most commonly observed variant (87.93%). A total of 25 haplogroups and 79 haplotypes were found in Kazak group, and Haplogroup D4 was the most common haplogroup (21.28%). Among the entire 79 haplotypes, 53 of them were observed for only once, 14 for twice. The haplotype diversity was 0.978 ± 0.005, and the nucleotide diversity was 0.17449. The detection of (CA)n and 9-bp deletion polymorphisms could improve the discrimination power of the mtDNA genetic marker. Moreover, Xinjiang Kazak group was compared with other previously reported groups to infer its genetic background. The present results revealed that Xinjiang Kazak ethnic group was genetically closer related to Xinjiang Uygur, Xinjiang Uzbek and Xinjiang Han populations. Meanwhile, our results also indicated the potential closer genetic relationships among Xinjiang Kazak group with Altaian Kazak as well as Xinjiang Xibe group. In conclusion, this novel mtDNA panel could be effectively utilized for forensic applications. Additionally, to further reveal the genetic background of Chinese Kazak group, more relevant populations and genetic markers should be incorporated in our future study.

RevDate: 2019-06-29

Aryaman J, Bowles C, Jones NS, et al (2019)

Mitochondrial Network Fragmentation Modulates Mutant mtDNA Accumulation Independently of Absolute Fission-Fusion Rates.

Genetics pii:genetics.119.302423 [Epub ahead of print].

Mitochondrial DNA (mtDNA) mutations cause severe congenital diseases but may also be associated with healthy aging. MtDNA is stochastically replicated and degraded, and exists within organelles which undergo dynamic fusion and fission. The role of the resulting mitochondrial networks in the time evolution of the cellular proportion of mutated mtDNA molecules (heteroplasmy), and cell-to-cell variability in heteroplasmy (heteroplasmy variance), remains incompletely understood. Heteroplasmy variance is particularly important since it modulates the number of pathological cells in a tissue. Here, we provide the first wide-reaching theoretical framework which bridges mitochondrial network and genetic states. We show that, under a range of conditions, the (genetic) rate of increase in heteroplasmy variance and de novo mutation are proportionally modulated by the (physical) fraction of unfused mitochondria, independently of the absolute fission-fusion rate. In the context of selective fusion, we show that intermediate fusion/fission ratios are optimal for the clearance of mtDNA mutants. Our findings imply that modulating network state, mitophagy rate and copy number to slow down heteroplasmy dynamics when mean heteroplasmy is low could have therapeutic advantages for mitochondrial disease and healthy aging.

RevDate: 2019-06-28

Levitskii S, Baleva MV, Chicherin I, et al (2019)

S. cerevisiae Strain Lacking Mitochondrial IF3 Shows Increased Levels of Tma19p during Adaptation to Respiratory Growth.

Cells, 8(7): pii:cells8070645.

After billions of years of evolution, mitochondrion retains its own genome, which gets expressed in mitochondrial matrix. Mitochondrial translation machinery rather differs from modern bacterial and eukaryotic cytosolic systems. Any disturbance in mitochondrial translation drastically impairs mitochondrial function. In budding yeast Saccharomyces cerevisiae, deletion of the gene coding for mitochondrial translation initiation factor 3 - AIM23, leads to an imbalance in mitochondrial protein synthesis and significantly delays growth after shifting from fermentable to non-fermentable carbon sources. Molecular mechanism underlying this adaptation to respiratory growth was unknown. Here, we demonstrate that slow adaptation from glycolysis to respiration in the absence of Aim23p is accompanied by a gradual increase of cytochrome c oxidase activity and by increased levels of Tma19p protein, which protects mitochondria from oxidative stress.

RevDate: 2019-06-28
CmpDate: 2019-06-28

Xie GL, Köhler F, Huang XC, et al (2019)

A novel gene arrangement among the Stylommatophora by the complete mitochondrial genome of the terrestrial slug Meghimatium bilineatum (Gastropoda, Arionoidea).

Molecular phylogenetics and evolution, 135:177-184.

Stylommatophora is a main clade of Gastropoda that encompasses approximately 112 gastropod families and may exceed a total of 30,000 species. Twenty-four complete stylommatophoran mitogenomes have been sequenced to date, yet our understanding of mitochondrial evolution in stylommatophorans is still in its infancy. To further expand the set of available mitogenomes, we sequenced the mitogenome of Meghimatium bilineatum (Arionoidea: Philomycidae), a widespread land slug in East Asia. This is the first report on a mitogenome of the superfamily Arionoidea, and indeed on a terrestrial slug. The mitogenome of Meghimatium bilineatum comprises 13,972 bp and exhibits a novel, highly distinctive gene arrangement among the Stylommatophora. Phylogenetic reconstructions based on the sequences of all protein-coding genes consistently recovered Meghimatium bilineatum as sister-group of the Succineidae. A phylogenetic reconstruction based on gene order, however, suggested a highly divergent tree topology, which is less credible when taking into account prior knowledge of stylommatophoran relationships. Our CREx (Common interval Rearrangement Explorer) analysis suggested that three successive events of tandem duplication random loss (TDRL) best explain the evolutionary process of gene order rearrangement in Meghimatium bilineatum from an ancestral stylommatophoran mitogenome. The present example offers new insights into the mechanisms of mitogenome rearrangements in gastropods at large and into the usefulness of mitogenomic gene order as a phylogenetic marker.

RevDate: 2019-06-28
CmpDate: 2019-06-28

Belaiba E, Marrone F, Vecchioni L, et al (2019)

An exhaustive phylogeny of the combtooth blenny genus Salaria (Pisces, Blenniidae) shows introgressive hybridization and lack of reciprocal mtDNA monophyly between the marine species Salaria basilisca and Salaria pavo.

Molecular phylogenetics and evolution, 135:210-221.

A comprehensive phylogeny of the genus Salaria based on mitochondrial and nuclear markers grouped the extant species of the genus in well-characterised marine and freshwater clades, thus rejecting the hypothesis of a polytypic origin of the freshwater Salaria populations and supporting the occurrence of a single invasion event of the inland waters by the genus. Based on both mitochondrial and nuclear DNA datasets, the Salaria species of the freshwater clade proved to be vicariant taxa originating from a common ancestor which could possibly spread throughout the circum-Mediterranean inland waters during the late Miocene Messinian salinity crisis, then experiencing a process of allopatric differentiation after the re-flooding of the Mediterranean basin. Within the marine clade, although the nuDNA datasets showed the existence of well-supported subclades in accordance to the morphological identification of the studied specimens, one of the two subclades obtained in the phylogenetic tree based on the mtDNA dataset included both S. basilisca and S. pavo specimens, thus failing to find the two species as reciprocally monophyletic. Such a mito-nuclear discordance is here ascribed to multiple mtDNA unidirectional introgression events from S. basilisca to S. pavo, and the molecular diversity pattern of the marine Salaria species is here ascribed to a Pleistocene speciation event nowadays partly concealed by the occurrence of introgressive hybridization phenomena between the two taxa. Our results urge for prudence when implementing DNA barcoding approaches since, in the presence of mito-nuclear discordance phenomena, single-marker mtDNA-only analyses might lead to significant misidentifications.

RevDate: 2019-06-28
CmpDate: 2019-06-28

Brunes TO, da Silva AJ, Marques-Souza S, et al (2019)

Not always young: The first vertebrate ancient origin of true parthenogenesis found in an Amazon leaf litter lizard with evidence of mitochondrial haplotypes surfing on the wave of a range expansion.

Molecular phylogenetics and evolution, 135:105-122.

In vertebrates, true parthenogenesis is found only in squamate reptiles and (mostly) originates via interspecific hybridization after secondary contact. In many cases, parthenogenesis is followed by an increase of ploidy, resulting in triploid lineages. Phylogenetic analyses derived from nuclear and maternally inherited markers can help to clarify the mechanisms of origin and the potential parental species involved. In the Amazon region, parthenogenetic lizards of the Loxopholis percarinatum complex are widely distributed, comprising both diploid and triploid clones. Recently, putative males of L. percarinatum were reported, suggesting the existence of bisexual populations based on morphological data. Here, we used mitochondrial and nuclear data to investigate the origin of parthenogenesis in Loxopholis. Mitochondrial DNA analysis revealed three major lineages: unisexual/2n, unisexual/3n and bisexual, the last of which comprised two sub-lineages placed as the sister taxon to the unisexual/3n lineage. Genetic divergence among the lineages was ∼10% but was lower between the unisexual/3n and bisexual lineages (∼6%). Both mtDNA and nuDNA indicated that individuals from the bisexual lineages might belong to a new species. Nuclear DNA evidence indicates that crossings occasionally occur between unisexual 2n and males from the new bisexual species. Phylogenetic analysis of nuDNA showed L. ferreirai as the closest described bisexual species to the complex. Our results revealed an ancient origin of parthenogenesis in the L. percarinatum complex, in contrast to most young (Pleistocene) parthenogenetic lizards described thus far. Two hybridization events seem to have been involved: the first event occurred in late Miocene, between the ancestral lineage ("A") of the new bisexual species (as a maternal species) and the ancestral lineage of L. ferreirai, as a paternal species of L. percarinatum 2n; and the second event occurred in Pliocene-Pleistocene, in a backcross between L. percarinatum 2n and a male from the common ancestor ("B") of the new bisexual species giving rise to the lineage of L. percarinatum 3n. With these results, we showed that L. percarinatum complex also includes, at least, one undescribed bisexual species in addition to the two known parthenogenetic lineages (2n and 3n). Finally, we present evidence that diploid individuals of L. percarinatum experienced an event of wide demographic expansion over the past million years under an allele surfing model.

RevDate: 2019-06-27
CmpDate: 2019-06-27

Hillebrand A, Matz JM, Almendinger M, et al (2018)

Identification of clustered organellar short (cos) RNAs and of a conserved family of organellar RNA-binding proteins, the heptatricopeptide repeat proteins, in the malaria parasite.

Nucleic acids research, 46(19):10417-10431.

Gene expression in mitochondria of Plasmodium falciparum is essential for parasite survival. The molecular mechanisms of Plasmodium organellar gene expression remain poorly understood. This includes the enigmatic assembly of the mitochondrial ribosome from highly fragmented rRNAs. Here, we present the identification of clustered organellar short RNA fragments (cosRNAs) that are possible footprints of RNA-binding proteins (RBPs) in Plasmodium organelles. In plants, RBPs of the pentatricopeptide repeat (PPR) class produce footprints as a consequence of their function in processing organellar RNAs. Intriguingly, many of the Plasmodium cosRNAs overlap with 5'-ends of rRNA fragments. We hypothesize that these are footprints of RBPs involved in assembling the rRNA fragments into a functioning ribosome. A bioinformatics search of the Plasmodium nuclear genome identified a hitherto unrecognized organellar helical-hairpin-repeat protein family that we term heptatricopeptide repeat (HPR) proteins. We demonstrate that selected HPR proteins are targeted to mitochondria in P. berghei and that one of them, PbHPR1, associates with RNA, but not DNA in vitro. A phylogenetic search identified HPR proteins in a wide variety of eukaryotes. We hypothesize that HPR proteins are required for processing and stabilizing RNAs in Apicomplexa and other taxa.

RevDate: 2019-06-27

Breda CNS, Davanzo GG, Basso PJ, et al (2019)

Mitochondria as central hub of the immune system.

Redox biology, 26:101255 pii:S2213-2317(19)30307-6 [Epub ahead of print].

Nearly 130 years after the first insights into the existence of mitochondria, new rolesassociated with these organelles continue to emerge. As essential hubs that dictate cell fate, mitochondria integrate cell physiology, signaling pathways and metabolism. Thus, recent research has focused on understanding how these multifaceted functions can be used to improve inflammatory responses and prevent cellular dysfunction. Here, we describe the role of mitochondria on the development and function of immune cells, highlighting metabolic aspects and pointing out some metabolic- independent features of mitochondria that sustain cell function.

RevDate: 2019-06-26

Ågren JA, Davies NG, KR Foster (2019)

Enforcement is central to the evolution of cooperation.

Nature ecology & evolution pii:10.1038/s41559-019-0907-1 [Epub ahead of print].

Cooperation occurs at all levels of life, from genomes, complex cells and multicellular organisms to societies and mutualisms between species. A major question for evolutionary biology is what these diverse systems have in common. Here, we review the full breadth of cooperative systems and find that they frequently rely on enforcement mechanisms that suppress selfish behaviour. We discuss many examples, including the suppression of transposable elements, uniparental inheritance of mitochondria and plastids, anti-cancer mechanisms, reciprocation and punishment in humans and other vertebrates, policing in eusocial insects and partner choice in mutualisms between species. To address a lack of accompanying theory, we develop a series of evolutionary models that show that the enforcement of cooperation is widely predicted. We argue that enforcement is an underappreciated, and often critical, ingredient for cooperation across all scales of biological organization.

RevDate: 2019-06-26

Sun N, Parrish RS, Calderone RA, et al (2019)

Unique, Diverged, and Conserved Mitochondrial Functions Influencing Candida albicans Respiration.

mBio, 10(3): pii:mBio.00300-19.

Candida albicans is an opportunistic fungal pathogen of major clinical concern. The virulence of this pathogen is intimately intertwined with its metabolism. Mitochondria, which have a central metabolic role, have undergone many lineage-specific adaptations in association with their eukaryotic host. A screen for lineage-specific genes identified seven such genes specific to the CTG clade of fungi, of which C. albicans is a member. Each is required for respiratory growth and is integral to expression of complex I, III, or IV of the electron transport chain. Two genes, NUO3 and NUO4, encode supernumerary subunits of complex I, whereas NUE1 and NUE2 have nonstructural roles in expression of complex I. Similarly, the other three genes have nonstructural roles in expression of complex III (QCE1) or complex IV (COE1 and COE2). In addition to these novel additions, an alternative functional assignment was found for the mitochondrial protein encoded by MNE1MNE1 was required for complex I expression in C. albicans, whereas the distantly related Saccharomyces cerevisiae ortholog participates in expression of complex III. Phenotypic analysis of deletion mutants showed that fermentative metabolism is unable to support optimal growth rates or yields of C. albicans However, yeast-hypha morphogenesis, an important virulence attribute, did not require respiratory metabolism under hypoxic conditions. The inability to respire also resulted in hypersensitivity to the antifungal fluconazole and in attenuated virulence in a Galleria mellonella infection model. The results show that lineage-specific adaptations have occurred in C. albicans mitochondria and highlight the significance of respiratory metabolism in the pathobiology of C. albicansIMPORTANCECandida albicans is an opportunistic fungal pathogen of major clinical concern. The virulence of this pathogen is intimately intertwined with its metabolic behavior, and mitochondria have a central role in that metabolism. Mitochondria have undergone many evolutionary changes, which include lineage-specific adaptations in association with their eukaryotic host. Seven lineage-specific genes required for electron transport chain function were identified in the CTG clade of fungi, of which C. albicans is a member. Additionally, examination of several highly diverged orthologs encoding mitochondrial proteins demonstrated functional reassignment for one of these. Deficits imparted by deletion of these genes revealed the critical role of respiration in virulence attributes of the fungus and highlight important evolutionary adaptations in C. albicans metabolism.

RevDate: 2019-06-25

Emelyantsev S, Prazdnova E, Chistyakov V, et al (2019)

Biological Effects of C60 Fullerene Revealed with Bacterial Biosensor-Toxic or Rather Antioxidant?.

Biosensors, 9(2): pii:bios9020081.

Nanoparticles have been attracting growing interest for both their antioxidant and toxic effects. Their exact action on cells strongly depends on many factors, including experimental conditions, preparation, and solvents used, which have contributed to the confusion regarding their safety and possible health benefits. In order to clarify the biological effects of the most abundant fullerene C60, its impact on the Escherichia coli model has been studied. The main question was if C60 would have any antioxidant influence on the cell and, if yes, whether and to which extent it would be concentration-dependent. An oxidative stress induced by adding hydrogen peroxide was measured with an E. coli MG1655 pKatG-lux strain sensor, with its time evolution being recorded in the presence of fullerene C60 suspensions of different concentrations. Optimal conditions for the fullerene C60 solubilization in TWEEN 80 2% aqueous solution, together with resulting aggregate sizes, were determined. Results obtained for the bacterial model can be extrapolated on eukaryote mitochondria. The ability of C60 to penetrate through biological membranes, conduct protons, and interact with free radicals is likely responsible for its protective effect detected for E. coli. Thus, fullerene can be considered as a mitochondria-targeted antioxidant, worth further researching as a prospective component of novel medications.

RevDate: 2019-06-25
CmpDate: 2019-06-25

Lassance JM, Svensson GP, Kozlov MV, et al (2019)

Pheromones and Barcoding Delimit Boundaries between Cryptic Species in the Primitive Moth Genus Eriocrania (Lepidoptera: Eriocraniidae).

Journal of chemical ecology, 45(5-6):429-439.

Animal classification is primarily based on morphological characters, even though these may not be the first to diverge during speciation. In many cases, closely related taxa are actually difficult to distinguish based on morphological characters alone, especially when there is no substantial niche separation. As a consequence, the diversity of certain groups is likely to be underestimated. Lepidoptera -moths and butterflies- represent the largest group of herbivorous insects. The extensive diversification in the group is generally assumed to have its origin in the spectacular radiation of flowering plants and the resulting abundance of ecological niches. However, speciation can also occur without strong ecological divergence. For example, reproductive isolation can evolve as the result of divergence in mate preference and the associated pheromone communication system. We combined pheromone trapping and genetic analysis to elucidate the evolutionary relationships within a complex of primitive moth species (Lepidoptera: Eriocraniidae). Mitochondrial and nuclear DNA markers provided evidence that Eriocrania semipurpurella, as currently defined by morphological characters, includes three cryptic species in Northern and Western Europe. Male moths of these cryptic species, as well as of the closely related E. sangii, exhibited relative specificity in terms of their attraction to specific ratios of two major pheromone components, (2S,6Z)-nonen-2-ol and (2R,6Z)-nonen-2-ol. Our data suggest strong assortative mating in these species in the absence of apparent niche separation, indicating that Eriocrania moths may represent an example of non-ecological speciation. Finally, our study argues in favour of combining pheromone investigations and DNA barcoding as powerful tools for identifying and delimitating species boundaries.

RevDate: 2019-06-26
CmpDate: 2019-06-26

Du Z, Ishikawa T, Liu H, et al (2019)

Phylogeography of the Assassin Bug Sphedanolestes impressicollis in East Asia Inferred From Mitochondrial and Nuclear Gene Sequences.

International journal of molecular sciences, 20(5): pii:ijms20051234.

The assassin bug, Sphedanolestes impressicollis (Hemiptera: Reduviidae), is widely distributed in East Asia. It is an ideal model for evaluating the effects of climatic fluctuation and geographical events on the distribution patterns of East Asian reduviids. Here, we used two mitochondrial genes and one nuclear gene to investigate the phylogeographic pattern of the assassin bug based on comprehensive sampling in China, Japan, South Korea, Vietnam, and Laos. High levels of genetic differentiation were detected among the geographic populations classified into the northern and southern groups. A significant correlation was detected between genetic and geographical distances. The East China Sea land bridge served as a "dispersal corridor" during Pleistocene glaciation. The estimated divergence time indicated that the northern group may have separated from the eastern Chinese populations when the sea level rapidly rose during the "Ryukyu Coral Sea Stage" and the East China Sea land bridge was completely submerged. Demographic history and ecological niche modeling suggested that appropriate climatic conditions may have accounted for the rapid spread across the Korean Peninsula and Japan during the late Pleistocene. Our study underscores the pivotal roles of the Pleistocene sea level changes and climatic fluctuations in determining the distribution patterns of East Asian reduviids.

RevDate: 2019-06-23

Havird JC, Noe GR, Link L, et al (2019)

Do angiosperms with highly divergent mitochondrial genomes have altered mitochondrial function?.

Mitochondrion pii:S1567-7249(19)30029-7 [Epub ahead of print].

Angiosperm mitochondrial (mt) genes are generally slow-evolving, but multiple lineages have undergone dramatic accelerations in rates of nucleotide substitution and extreme changes in mt genome structure. While molecular evolution in these lineages has been investigated, very little is known about their mt function. Some studies have suggested altered respiration in individual taxa, although there are several reasons why mt variation might be neutral in others. Here, we develop a new protocol to characterize respiration in isolated plant mitochondria and apply it to species of Silene with mt genomes that are rapidly evolving, highly fragmented, and exceptionally large (~11 Mbp). This protocol, complemented with traditional measures of plant fitness, cytochrome c oxidase activity assays, and fluorescence microscopy, was also used to characterize inter- and intraspecific variation in mt function. Contributions of the individual "classic" OXPHOS complexes, the alternative oxidase, and external NADH dehydrogenases to overall mt respiratory flux were found to be similar to previously studied angiosperms with more typical mt genomes. Some differences in mt function could be explained by inter- and intraspecific variation. This study suggests that Silene species with peculiar mt genomes still show relatively normal mt respiration. This may be due to strong purifying selection on mt variants, coevolutionary responses in the nucleus, or a combination of both. Future experiments should explore such questions using a comparative framework and investigating other lineages with unusual mitogenomes.

RevDate: 2019-06-21
CmpDate: 2019-06-21

Ma X, Yao L, Yang B, et al (2017)

RNAi-mediated silencing of a pyruvate dehydrogenase kinase enhances triacylglycerol biosynthesis in the oleaginous marine alga Nannochloropsis salina.

Scientific reports, 7(1):11485.

Oleaginous microalgae have been emerging as the third-generation feedstocks for biofuel production. Genetic manipulation for improving triacylglycerol (TAG) accumulation represents a promising approach towards the economics of microalgal biofuels. Acetyl-CoA, the essential carbon precursor for de novo fatty acid biosynthesis, can be derived from pyruvate catalyzed by pyruvate dehydrogenase, which is negatively regulated by pyruvate dehydrogenase kinase (PDK). In the present study, we characterized a PDK gene (NsPDK) from Nannochloropsis salina. Subcellular localization assay assisted by green fluorescence protein (GFP) fusion indicated the localization of NsPDK in mitochondria of N. salina cells. NsPDK knockdown via RNA interference strategy attenuated NsPDK expression at the mRNA level and its enzymatic activity in vivo, leading to faster TAG accumulation without compromising cell growth under high light stress conditions. Interestingly, the TAG increase was accompanied by a decline in membrane polar lipids. NsPDK knockdown also altered fatty acid profile in N. salina. Furthermore, transcriptional analysis suggested that the carbon metabolic pathways might be influenced by NsPDK knockdown leading to diverted carbon flux towards TAG synthesis. Taken together, our results demonstrate the role of NsPDK in regulating TAG accumulation and provide valuable insights into future manipulation of oleaginous microalgae for improving biofuel production.

RevDate: 2019-06-20

Gerlach L, Gholami O, Schürmann N, et al (2019)

Folding of β-Barrel Membrane Proteins into Lipid Membranes by Site-Directed Fluorescence Spectroscopy.

Methods in molecular biology (Clifton, N.J.), 2003:465-492.

Protein-lipid interactions are important for folding and membrane insertion of integral membrane proteins that are composed either of α-helical or of β-barrel structure in their transmembrane domains. While α-helical transmembrane proteins fold co-translationally while they are synthesized by a ribosome, β-barrel transmembrane proteins (β-TMPs) fold and insert posttranslationally-in bacteria after translocation across the cytoplasmic membrane, in cell organelles of eukaryotes after import across the outer membrane of the organelle. β-TMPs can be unfolded in aqueous solutions of chaotropic denaturants like urea and spontaneously refold upon denaturant dilution in the presence of preformed lipid bilayers. This facilitates studies on lipid interactions during folding into lipid bilayers. For several β-TMPs, the kinetics of folding has been reported as strongly dependent on protein-lipid interactions. The kinetics of adsorption/insertion and folding of β-TMPs can be monitored by fluorescence spectroscopy. These fluorescence methods are even more powerful when combined with site-directed mutagenesis for the preparation of mutants of a β-TMP that are site-specifically labeled with a fluorophore or a fluorophore and fluorescence quencher or fluorescence resonance energy acceptor. Single tryptophan or single cysteine mutants of the β-TMP allow for the investigation of local protein-lipid interactions, at specific regions within the protein. To examine the structure formation of β-TMPs in a lipid environment, fluorescence spectroscopy has been used for double mutants of β-TMPs that contain a fluorescent tryptophan and a spin-label, covalently attached to a cysteine as a fluorescence quencher. The sites of mutation are selected so that the tryptophan is in close proximity to the quencher at the cysteine only when the β-TMP is folded. In a folding experiment, the evolution of fluorescence quenching as a function of time at specific sites within the protein can provide important information on the folding mechanism of the β-TMP. Here, we report protocols to examine membrane protein folding for two β-TMPs in a lipid environment, the outer membrane protein A from Escherichia coli, OmpA, and the voltage-dependent anion-selective channel, human isoform 1, hVDAC1, from mitochondria.

RevDate: 2019-06-20

Krasovec M, Sanchez-Brosseau S, G Piganeau (2019)

First estimation of the spontaneous mutation rate in Diatoms.

Genome biology and evolution pii:5520952 [Epub ahead of print].

Mutations are the origin of genetic diversity, and the mutation rate is a fundamental parameter to understand all aspects of molecular evolution. The combination of mutation-accumulation experiments and high throughput sequencing enabled the estimation of mutation rates in most model organisms, but several major eukaryotic lineages remain unexplored. Here, we report the first estimation of the spontaneous mutation rate in a model unicellular eukaryote from the Stramenopile kingdom, the diatom Phaeodactylum tricornutum (strain RCC2967). We sequenced 36 mutation accumulation lines for an average of 181 generations per line and identified 156 de novo mutations. The base substitution mutation rate per site per generation is μbs= 4.77x10-10 and the insertion-deletion mutation rate is μid= 1.58x10-11. The mutation rate varies as a function of the nucleotide context and is biased towards an excess of mutations from GC to AT, consistent with previous observations in other species. Interestingly, the mutation rates between the genomes of organelles and the nucleus differ, with a significantly higher mutation rate in the mitochondria. This confirms previous claims based on indirect estimations of the mutation rate in mitochondria of photosynthetic eukaryotes that acquired their plastid through a secondary endosymbiosis. This novel estimate enables us to infer the effective population size of P. tricornutum to be Ne∼8.72x106.

RevDate: 2019-06-18

Nieuwenhuis M, van de Peppel LJJ, Bakker FT, et al (2019)

Enrichment of G4DNA and a large inverted repeat coincide in the mitochondrial genomes of Termitomyces.

Genome biology and evolution pii:5519768 [Epub ahead of print].

Mitochondria retain their own genome, a hallmark of their bacterial ancestry. Mitochondrial genomes (mtDNA) are highly diverse in size, shape and structure, despite their conserved function across most eukaryotes. Exploring extreme cases of mtDNA architecture can yield important information on fundamental aspects of genome biology. We discovered that the mitochondrial genomes of a basidiomycete fungus (Termitomyces spp.) contain an inverted repeat (IR), a duplicated region half the size of the complete genome. In addition, we found an abundance of sequences capable of forming G-quadruplexes (G4DNA); structures that can disrupt the double helical formation of DNA. G4DNA is implicated in replication fork stalling, double-stranded breaks, altered gene expression, recombination, and other effects. To determine whether this occurrence of IR and G4DNA was correlated within the genus Termitomyces, we reconstructed the mitochondrial genomes of eleven additional species including representatives of several closely related genera. We show that the mtDNA of all sampled species of Termitomyces and its sister group, represented by the species Tephrocybe rancida and Blastosporella zonata, are characterised by a large inverted repeat and enrichment of G4DNA. To determine whether high mitochondrial G4DNA content is common in fungi, we conducted the first broad survey of G4DNA content in fungal mtDNA, revealing it to be a highly variable trait. The results of this study provide important direction for future research on the function and evolution of G4DNA and organellar IRs.

RevDate: 2019-06-17
CmpDate: 2019-06-17

Karagozlu MZ, An HE, Park SH, et al (2019)

Comparative analyses of the three complete mitochondrial genomes from forensic important beetle genus Dermestes with phylogenetic relationships.

Gene, 706:146-153.

Necrophagous Dermestes species have high forensic importance in relation to the estimation of elapsed time since death or death season. To further supplement the genome-level features for related species, the complete mitochondrial genome (mitogenome) of Dermestes species D. essellatocollis, D. frischii and D. coarctatus are amplified, sequenced, annotated, analyzed, and compared with other twelve species of the infraorder Bostrichoidea. The mitochondrial genomes were typical circular molecules with 16,218, 15,873 and 15,873 bp in length, respectively. They included 13 protein coding genes, two rRNAs, and 22 tRNAs, as well as the putative control region. The gene orders and orientations are identical to those of other recorded bostrichiformian species and had the ancestral insect gene composition. Furthermore, phylogenetic analyses based on all the mitochondrial protein coding genes for 13 Bostrichoidea and 16 outgroup taxa were performed using Bayesian and Maximum Likelihood analyses. The inferred trees indicate that the genus Dermestes is monophyletic. The monophyly of infraorder Bostrichiformia is not supported. This study provides genomic data for mitochondrial genome library of the genus Dermestes to investigate evolutionary and systematic studies.

RevDate: 2019-06-17
CmpDate: 2019-06-17

Dufresnes C, Beddek M, Skorinov DV, et al (2019)

Diversification and speciation in tree frogs from the Maghreb (Hyla meridionalis sensu lato), with description of a new African endemic.

Molecular phylogenetics and evolution, 134:291-299.

Comparative molecular studies emphasized a new biogeographic paradigm for the terrestrial fauna of North Africa, one of the last uncharted ecoregions of the Western Palearctic: two independent east-west divisions across the Maghreb. Through a comprehensive phylogeography, we assessed how this model suits the genetic diversification documented for the tree frog Hyla meridionalis sensu lato. Analyses of mtDNA variation and thousands of nuclear loci confirmed the old split (low-Pliocene) between Tunisian and Algerian populations. These lineages meet but barely admix in the eastern Maghreb (Algerian-Tunisian border), a sign of putatively advanced reproductive isolation. In the western Maghreb, we report a Pleistocene divergence between Moroccan and Algerian populations. Tree frogs thus follow both predictions: a double east-west break that gave rise to two suture zones characteristic of North-African phylogeography. Moreover, some intraspecific mtDNA variation is not mirrored by the nuclear data, emphasizing that evolutionary units should always be designated by multilocus approaches. Last but not least, we describe the Tunisian lineage as a new species endemic to Africa.

RevDate: 2019-06-17
CmpDate: 2019-06-17

Jowers MJ, Sánchez-Ramírez S, Lopes S, et al (2019)

Unravelling population processes over the Late Pleistocene driving contemporary genetic divergence in Palearctic buzzards.

Molecular phylogenetics and evolution, 134:269-281.

Population range expansions and contractions as a response to climate and habitat change throughout the Quaternary are known to have contributed to complex phylogenetic and population genetic events. Speciation patterns and processes in Palearctic buzzards (genus Buteo) are a long-standing example of morphological and genetic data incongruence, attributed to panmixia, habitat range shifts, contact zones, and climate change. Here we assess the systematics, phylogeography and population genetic structure of three nominal species of Palearctic buzzards, Buteo buteo (including B. b. vulpinus), B. rufinus (including B. r. cirtensis) and B. hemilasius. Phylogenetic analyses inferred from mitochondrial data recover B. hemilasius as sister to the sister clades B. r. rufinus and B. buteo complex (B. b. buteo, B. b. vulpinus, but also including B. r. cirtensis). In contrast, we find an unresolved genetic delimitation inferred from four nuclear loci, suggesting an ancestral genetic pool for all species. Time-trees suggest population contractions and expansions throughout the Pleistocene, which likely reflect habitat change and contrasting ecological niche requirements between species. Microsatellite-based extended Bayesian skyline plots reveal relatively constant population sizes for B. hemilasius, B. r. rufinus, and B. b. vulpinus, in contrast to a dramatic population expansion in B. r. cirtensis within the last 3 kya. Overall, our study illustrates how complex population processes over the Late Pleistocene have shaped the patterns of genetic divergence in Palearctic buzzards, due to the joint effects of shared ancestral polymorphisms, population expansions and contractions, with hybridization at contact zones leading to admixture and introgression.

RevDate: 2019-06-17
CmpDate: 2019-06-17

Tang Y, Li C, Wanghe K, et al (2019)

Convergent evolution misled taxonomy in schizothoracine fishes (Cypriniformes: Cyprinidae).

Molecular phylogenetics and evolution, 134:323-337.

Highly specialized grade (HSG; genera Gymnocypris, Oxygymnocypris, Schizopygopsis, Platypharodon and Chuanchia) of the Schizothoracinae (Cypriniformes: Cyprinidae) are endemic to the Qinghai-Tibet Plateau (QTP). Previously, two distinct ecomorphs were recognized according to trophic traits. One was a limnetic omnivore with normal lower jaw morphology, terminal mouth, and moderate or dense gill rakers, mostly inhabiting in open water of lakes, including Gymnocypris and Oxygymnocypris. Another was a benthic feeder with inferior mouth, sparse gill rakers and sharp horny sheath on the lower jaw for scraping of attached prey off hard substrates, including Schizopygopsis, Platypharodon and Chuanchia. However, traditional taxonomy of HSG based on these trophic traits presented extensive conflicts with the molecular studies in recent years. The possible cause could be convergent evolution in morphology, retention of ancestral polymorphisms or mitochondrial introgression, but these hypotheses could not be assessed due to incomplete taxon sampling and only mitochondrial data employed in previous works. Here, we conducted the most comprehensive molecular analysis on HSG fishes to date, using four mitochondrial loci and 152,464 genome-wide SNPs, and including 21 of 24 putative species and one undescribed Schizopygopsis species. Both SNP and mtDNA trees confirmed extensive paraphyly of genera Gymnocypris and Schizopygopsis, where species often were clustered together by watershed instead of by genus. Basal split into the north clade B and the south clade C (ca. 3.03 Ma) approximately by the Tanggula-Tanitawen Mountains in SLAF tree coincided with a violent uplift of the QTP during the phase A of 'Qingzang movement' (ca. 3.6 Ma). Ancestral state reconstruction of the trophic ecomorph showed that the limnetic omnivore ecomorph had evolved repeatedly in clade B and C. Furthermore, we presented a striking case of convergent evolution between two 'subspecies' Gymnocypris chui chui and G. chui longimandibularis, which had diverged as early as two million years ago (ca. 2.42 Ma). Ecological analyses revealed that similar food utilization, particularly in zooplankton, was the main underlying driving force. This work showed an example of taxonomy with the most extensive errors at the genus/species levels due to convergent evolution and suggested that trophic traits could be misleading in fish taxonomy. Therefore, we propose a major generic revision for HSG species.

RevDate: 2019-06-16

Bloomfield G (2019)

The molecular foundations of zygosis.

Cellular and molecular life sciences : CMLS pii:10.1007/s00018-019-03187-1 [Epub ahead of print].

Zygosis is the generation of new biological individuals by the sexual fusion of gamete cells. Our current understanding of eukaryotic phylogeny indicates that sex is ancestral to all extant eukaryotes. Although sexual development is extremely diverse, common molecular elements have been retained. HAP2-GCS1, a protein that promotes the fusion of gamete cell membranes that is related in structure to certain viral fusogens, is conserved in many eukaryotic lineages, even though gametes vary considerably in form and behaviour between species. Similarly, although zygotes have dramatically different forms and fates in different organisms, diverse eukaryotes share a common developmental programme in which homeodomain-containing transcription factors play a central role. These common mechanistic elements suggest possible common evolutionary histories that, if correct, would have profound implications for our understanding of eukaryogenesis.

RevDate: 2019-06-15

Reis LMD, Adamoski D, Ornitz Oliveira Souza R, et al (2019)

Dual inhibition of glutaminase and carnitine palmitoyltransferase decreases growth and migration of glutaminase inhibition-resistant triple-negative breast cancer cells.

The Journal of biological chemistry, 294(24):9342-9357.

Triple-negative breast cancers (TNBCs) lack progesterone and estrogen receptors and do not have amplified human epidermal growth factor receptor 2, the main therapeutic targets for managing breast cancer. TNBCs have an altered metabolism, including an increased Warburg effect and glutamine dependence, making the glutaminase inhibitor CB-839 therapeutically promising for this tumor type. Accordingly, CB-839 is currently in phase I/II clinical trials. However, not all TNBCs respond to CB-839 treatment, and the tumor resistance mechanism is not yet fully understood. Here we classified cell lines as CB-839-sensitive or -resistant according to their growth responses to CB-839. Compared with sensitive cells, resistant cells were less glutaminolytic and, upon CB-839 treatment, exhibited a smaller decrease in ATP content and less mitochondrial fragmentation, an indicator of poor mitochondrial health. Transcriptional analyses revealed that the expression levels of genes linked to lipid metabolism were altered between sensitive and resistant cells and between breast cancer tissues (available from The Cancer Genome Atlas project) with low versus high glutaminase (GLS) gene expression. Of note, CB-839-resistant TNBC cells had increased carnitine palmitoyltransferase 2 (CPT2) protein and CPT1 activity levels. In agreement, CB-839-resistant TNBC cells mobilized more fatty acids into mitochondria for oxidation, which responded to AMP-activated protein kinase and acetyl-CoA carboxylase signaling. Moreover, chemical inhibition of both glutaminase and CPT1 decreased cell proliferation and migration of CB-839-resistant cells compared with single inhibition of each enzyme. We propose that dual targeting of glutaminase and CPT1 activities may have therapeutic relevance for managing CB-839-resistant tumors.

RevDate: 2019-06-14

Pan Z, Ren X, Zhao H, et al (2019)

A Mitochondrial Transcription Termination Factor, ZmSmk3, Is Required for nad1 Intron4 and nad4 Intron1 Splicing and Kernel Development in Maize.

G3 (Bethesda, Md.) pii:g3.119.400265 [Epub ahead of print].

The expression systems of the mitochondrial genes are derived from their bacterial ancestors, but have evolved many new features in their eukaryotic hosts. Mitochondrial RNA splicing is a complex process regulated by families of nucleus-encoded RNA-binding proteins, few of which have been characterized in maize (Zea mays L.). Here, we identified the Zea mays small kernel3 (Zmsmk3) candidate gene, which encodes a mitochondrial transcription termination factor (mTERF) containing two mTERF motifs, which is conserved in monocotyledon; and the target introns were also quite conserved during evolution between monocotyledons and dicotyledons. The mutations of Zmsmk3 led to arrested embryo and endosperm development, resulting in small kernels. A transcriptome of 12 days after pollination endosperm analysis revealed that the starch biosynthetic pathway and the zein gene family were down-regulated in the Zmsmk3 mutant kernels. ZmSMK3 is localized in mitochondria. The reduced expression of ZmSmk3 in the mutant resulted in the splicing deficiency of mitochondrial nad4 intron1 and nad1 intron4, causing a reduction in complex I assembly and activity, impairing mitochondria structure and activating the alternative respiratory pathway. So, the results suggest that ZmSMK3 is required for the splicing of nad4 intron 1 and nad1 intron 4, complex I assembly and kernel development in maize.

RevDate: 2019-06-14

Gerlitz M, Knopp M, Kapust N, et al (2018)

Elusive data underlying debate at the prokaryote-eukaryote divide.

Biology direct, 13(1):21 pii:10.1186/s13062-018-0221-x.

BACKGROUND: The origin of eukaryotic cells was an important transition in evolution. The factors underlying the origin and evolutionary success of the eukaryote lineage are still discussed. One camp argues that mitochondria were essential for eukaryote origin because of the unique configuration of internalized bioenergetic membranes that they conferred to the common ancestor of all known eukaryotic lineages. A recent paper by Lynch and Marinov concluded that mitochondria were energetically irrelevant to eukaryote origin, a conclusion based on analyses of previously published numbers of various molecules and ribosomes per cell and cell volumes as a presumed proxy for the role of mitochondria in evolution. Their numbers were purportedly extracted from the literature.

RESULTS: We have examined the numbers upon which the recent study was based. We report that for a sample of 80 numbers that were purportedly extracted from the literature and that underlie key inferences of the recent study, more than 50% of the values do not exist in the cited papers to which the numbers are attributed. The published result cannot be independently reproduced. Other numbers that the recent study reports differ inexplicably from those in the literature to which they are ascribed. We list the discrepancies between the recently published numbers and the purported literature sources of those numbers in a head to head manner so that the discrepancies are readily evident, although the source of error underlying the discrepancies remains obscure.

CONCLUSION: The data purportedly supporting the view that mitochondria had no impact upon eukaryotic evolution data exhibits notable irregularities. The paper in question evokes the impression that the published numbers are of up to seven significant digit accuracy, when in fact more than half the numbers are nowhere to be found in the literature to which they are attributed. Though the reasons for the discrepancies are unknown, it is important to air these issues, lest the prominent paper in question become a point source of a snowballing error through the literature or become interpreted as a form of evidence that mitochondria were irrelevant to eukaryote evolution.

REVIEWERS: This article was reviewed by Eric Bapteste, Jianzhi Zhang and Martin Lercher.

RevDate: 2019-06-13
CmpDate: 2019-06-10

Araujo NS, MC Arias (2019)

Mitochondrial genome characterization of Melipona bicolor: Insights from the control region and gene expression data.

Gene, 705:55-59.

The stingless bee Melipona bicolor is the only bee in which true polygyny occurs. Its mitochondrial genome was first sequenced in 2008, but it was incomplete and no information about its transcription was known. We combined short and long reads of M. bicolor DNA with RNASeq data to obtain insights about mitochondrial evolution and gene expression in bees. The complete genome has 15,001 bp, including a control region of 255 bp that contains all conserved structures described in honeybees with the highest AT content reported so far for bees (98.1%), displaying a compact but functional region. Gene expression control is similar to other insects however unusual patterns of expression may suggest the existence of different isoforms for the mitochondrially encoded 12S rRNA. Results reveal unique and shared features of the mitochondrial genome in terms of sequence evolution and gene expression making M. bicolor an interesting model to study mitochondrial genomic evolution.

RevDate: 2019-06-13
CmpDate: 2019-06-11

Ni Y, Ma X, Hu W, et al (2019)

New lineages and old species: Lineage diversity and regional distribution of Moina (Crustacea: Cladocera) in China.

Molecular phylogenetics and evolution, 134:87-98.

The distribution and genetic diversity of freshwater zooplankton is understudied in the Eastern Palearctic. Here, we explored the lineage diversity and regional distribution of the genus Moina in China. Members of this genus are often keystone components of freshwater ecosystems and have been frequently subjected to toxicological and physiological studies. Four species of Moina were identified, based on morphology, in 50 of 113 Chinese water bodies examined, and their phylogenetic position was analyzed using both a mitochondrial (mitochondrial cytochrome c oxidase subunit I; COI) and a nuclear marker (the nuclear internal transcribed spacer; ITS-1). Both molecular markers identified four clades corresponding broadly to the morphological species. Mitochondrial DNA analysis showed the presence of four species complexes with eleven lineages across China, five of which were new. However, some lineages (and even individual haplotypes) were widespread in Eurasia, suggesting an ability to disperse over long distances. In contrast, a few lineages exhibited restricted distributions. The nuclear phylogeny also recognized four species of Moina within China and seven very distinct clades. Interestingly, one specimen possessing Moina cf. micrura mtDNA had ITS-1 alleles of the M. cf. brachiata clade. This discordance between mtDNA and nuclear ITS-1 phylogenies is indicative of interspecific introgression and hybridization. Additionally, our COI phylogeny showed apparent paraphyly in two Moina species groups, suggesting introgression of their mitochondrial genomes. Our data shows the regional distribution/diversity of the Moina species complex in a Eurasian context.

RevDate: 2019-06-13
CmpDate: 2019-06-10

Rydin C, Wikström N, B Bremer (2017)

Conflicting results from mitochondrial genomic data challenge current views of Rubiaceae phylogeny.

American journal of botany, 104(10):1522-1532.

PREMISE OF THE STUDY: Reconstruction of plant phylogeny has heavily relied on single-gene or multigene plastid data. New sequencing methods have led to an increasing number of studies based on data from the entire plastid, but the mitochondrion has rarely been used to infer plant phylogeny because of an assumed information poverty and demonstrated lateral transfer of mitochondrial gene regions between distantly related species.

METHODS: We explored phylogenetic information from the plant mitochondrion using 57 representatives of the species-rich coffee family as study system and assessed consistency with previous results based (mostly) on plastid data.

KEY RESULTS: We showed that the mitochondrial genome can provide structured and statistically significant information on plant phylogeny. While most of our results are consistent with those based on plastid data, some surprising and statistically significant conflicts emerge, and our study demonstrates with striking clarity that the phylogeny of Rubiaceae is far from resolved.

CONCLUSIONS: It appears unlikely that conflicts between results retrieved from the different genomic compartments would be restricted to Rubiaceae. Rather, they are probably a general phenomenon and an important factor behind longstanding "difficult" phylogenetic questions. The biological processes responsible for the conflicting results detected here are unclear, but some conflicts are likely caused by hybridization events that occurred tens of millions of years ago. Whether such ancient events can be reconstructed based on molecular data from extant plants remains to be seen, but future studies of the nuclear genome may provide a way forward.

RevDate: 2019-06-13
CmpDate: 2019-06-10

Kaur B, Valach M, Peña-Diaz P, et al (2018)

Transformation of Diplonema papillatum, the type species of the highly diverse and abundant marine microeukaryotes Diplonemida (Euglenozoa).

Environmental microbiology, 20(3):1030-1040.

Diplonema papillatum is the type species of diplonemids, which are among the most abundant and diverse heterotrophic microeukaryotes in the world's oceans. Diplonemids are also known for a unique form of post-transcriptional processing in mitochondria. However, the lack of reverse genetics methodologies in these protists has hampered elucidation of their cellular and molecular biology. Here we report a protocol for D. papillatum transformation. We have identified several antibiotics to which D. papillatum is sensitive and thus are suitable selectable markers, and focus in particular on puromycin. Constructs were designed encoding antibiotic resistance markers, fluorescent tags, and additional genomic sequences from D. papillatum to facilitate vector integration into chromosomes. We established conditions for effective electroporation, and demonstrate that electroporated constructs can be stably integrated in the D. papillatum nuclear genome. In D. papillatum transformants, the heterologous puromycin resistance gene is transcribed into mRNA and translated into protein, as determined by Southern hybridization, reverse transcription, and Western blot analyses. This is the first documented case of transformation in a euglenozoan protist outside the well-studied kinetoplastids, making D. papillatum a genetically tractable organism and potentially a model system for marine microeukaryotes.

RevDate: 2019-06-10

Schober AF, Rï O Bï Rtulos C, Bischoff A, et al (2019)

Organelle Studies and Proteome Analyses on Mitochondria and Plastids Fractions from the Diatom Thalassiosira pseudonana.

Plant & cell physiology pii:5513118 [Epub ahead of print].

Diatoms are unicellular algae and evolved by secondary endosymbiosis, a process in which a red alga-like eukaryote was engulfed by a heterotrophic eukaryotic cell. This gave rise to plastids of remarkable complex architecture and ultrastructure that require elaborate protein importing, trafficking, signaling and intracellular cross-talk pathways. Studying both plastids and mitochondria and their distinctive physiological pathways in organello may greatly contribute to our understanding of photosynthesis, mitochondrial respiration, and diatom evolution. The isolation of such complex organelles, however, is still demanding, and existing protocols are either limited to a few species (for plastids) or have not been reported for diatoms so far (for mitochondria). In this work, we present the first isolation protocol for mitochondria from the model diatom Thalassiosira pseudonana. Apart from that, we extended the protocol so that it is also applicable for the purification of a high-quality plastids fraction, and provide detailed structural and physiological characterizations of the resulting organelles. Isolated mitochondria were structurally intact, showed clear evidence of mitochondrial respiration, but the fractions still contained residual cell fragments. In contrast, plastid isolates were virtually free of cellular contaminants, featured structurally preserved thylakoids performing electron transport, but lost most of their stromal components as concluded from western blots and mass spectrometry. LC-ESI-MS/MS studies on mitochondria and thylakoids, moreover, allowed detailed proteome analyses which resulted in extensive proteome maps for both plastids and mitochondria thus helping us to broaden our understanding of organelle metabolism and functionality in diatoms.

RevDate: 2019-06-06

Edgar JA (2019)

L-Ascorbic Acid and the Evolution of Multicellular Eukaryotes.

Journal of theoretical biology pii:S0022-5193(19)30228-0 [Epub ahead of print].

The lifeless earth was formed around 4.5 billion years ago and the first anaerobic unicellular "organisms" may have appeared half a billion years later. Despite subsequent prokaryotes (bacteria and archaea) evolving quite complex biochemistry and some eukaryote characteristics, the transition from unicellular prokaryotes to multicellular, aerobic eukaryotes took a further 2.5 billion years to begin. The key factor or factors that eventually caused this long-delayed transition is a question that has been a focus of considerable research and a topic of discussion over many years. On the basis of the extensive literature available and consideration of some of the characteristics that distinguish multicellular eukaryotes from prokaryotes, it is proposed that, as well as the development of oxygenic photosynthesis producing high levels of environmental oxygen and the formation of vital organelles such as aerobic adenosine triphosphate-generating mitochondria, the concurrent evolution of the L-ascorbic acid redox system should be considered as a key factor that led to the evolution of multicellular eukaryotes and it remains vitally involved in the maintenance of multicellularity and many other eukaryote characteristics.

RevDate: 2019-06-04

Havird JC, Forsythe ES, Williams AM, et al (2019)

Selfish Mitonuclear Conflict.

Current biology : CB, 29(11):R496-R511.

Mitochondria, a nearly ubiquitous feature of eukaryotes, are derived from an ancient symbiosis. Despite billions of years of cooperative coevolution - in what is arguably the most important mutualism in the history of life - the persistence of mitochondrial genomes also creates conditions for genetic conflict with the nucleus. Because mitochondrial genomes are present in numerous copies per cell, they are subject to both within- and among-organism levels of selection. Accordingly, 'selfish' genotypes that increase their own proliferation can rise to high frequencies even if they decrease organismal fitness. It has been argued that uniparental (often maternal) inheritance of cytoplasmic genomes evolved to curtail such selfish replication by minimizing within-individual variation and, hence, within-individual selection. However, uniparental inheritance creates conditions for cytonuclear conflict over sex determination and sex ratio, as well as conditions for sexual antagonism when mitochondrial variants increase transmission by enhancing maternal fitness but have the side-effect of being harmful to males (i.e., 'mother's curse'). Here, we review recent advances in understanding selfish replication and sexual antagonism in the evolution of mitochondrial genomes and the mechanisms that suppress selfish interactions, drawing parallels and contrasts with other organelles (plastids) and bacterial endosymbionts that arose more recently. Although cytonuclear conflict is widespread across eukaryotes, it can be cryptic due to nuclear suppression, highly variable, and lineage-specific, reflecting the diverse biology of eukaryotes and the varying architectures of their cytoplasmic genomes.

RevDate: 2019-06-10

Wu Q, Lan Y, Cao X, et al (2019)

Characterization and diverse evolution patterns of glycerol-3-phosphate dehydrogenase family genes in Dunaliella salina.

Gene, 710:161-169 pii:S0378-1119(19)30543-8 [Epub ahead of print].

The glycerol-3-phosphate dehydrogenase (GPD) gene family plays a major role in glycerol synthesis and adaptation to abiotic stresses. Few studies on GPD family genes from the halotolerant algae Dunaliella salina are available. In this study, seven DsaGPD genes were identified by mining D. salina sequencing data. Among them, DsaGPD5 contained the canonical NAD+-GPD protein domain, called si-GPD. In comparison, DsaGPD1-4 not only contained the canonical NAD+-GPD domain but also a unique domain, the haloacid dehalogenase (HAD)-like superfamily domain, in their N-terminal region, called bi-GPD. DsaGPD6, 7 contained the FAD+-GPD domain. In the transient expression system, DsaGPD1, 3, 4 were found in the cytosol of Arabidopsis thaliana protoplast, DsaGPD2, 5 in the chloroplast, and DsaGPD6, 7 in the mitochondria. MEME analysis showed that six conserved motifs were present in both si-GPDs and bi-GPDs, whereas seven highly conserved motifs were only present in bi-GPDs. The quantitative real-time PCR results showed significant induction of the DsaGPD genes under abiotic stresses, indicating their tolerance-related role in D. salina. DsaGPD2 and DsaGPD5 may be the osmoregulator form and glyceride form in the chloroplast, respectively. The evolutionary forces acting on si-GPDs and bi-GPDs were different in the same organism: bi-GPDs were under purifying selection, while si-GPDs were mainly under positive selection. Furthermore, evolution of the N_HAD domain and C_GPD domain in bi-GPDs is highly correlated. In summary, this study characterizes DsaGPD gene family members and provides useful information for elucidating the salt tolerance mechanism in D. salina.

RevDate: 2019-06-01

Sihali-Beloui O, Aroune D, Benazouz F, et al (2019)

A hypercaloric diet induces hepatic oxidative stress, infiltration of lymphocytes, and mitochondrial reshuffle in Psammomys obesus, a murine model of insulin resistance.

Comptes rendus biologies pii:S1631-0691(19)30041-1 [Epub ahead of print].

The aim of this study was to show, for the first time, the effect of a hypercaloric diet on the mitochondrial reshuffle of hepatocytes during the progression from steatosis to steatohepatitis to cirrhosis in Psammomys obesus, a typical animal model of the metabolic syndrome. Metabolic and oxidative stresses were induced by feeding the animal through a standard laboratory diet (SD) for nine months. Metabolic parameters, liver malondialdehyde (MDA) and glutathione (GSH), were evaluated. The pathological evolution was examined by histopathology and immunohistochemistry, using CD3 and CD20 antibodies. The dynamics of the mitochondrial structure was followed by transmission electron microscopy. SD induced a steatosis in this animal that evolved under the effect of oxidative and metabolic stress by the appearance of adaptive inflammation and fibrosis leading the animal to the cirrhosis stage with serious hepatocyte damage by the triggering, at first the mitochondrial fusion-fission cycles, which attempted to maintain the mitochondria intact and functional, but the hepatocellular oxidative damage was increased inducing a vicious circle of mitochondrial alteration and dysfunction and their elimination by mitophagy. P. obesus is an excellent animal model of therapeutic research that targets mitochondrial dysfunction in the progression of steatosis.

RevDate: 2019-05-31

Yin HZ, Wang HL, Ji SG, et al (2019)

Rapid Intramitochondrial Zn2+ Accumulation in CA1 Hippocampal Pyramidal Neurons After Transient Global Ischemia: A Possible Contributor to Mitochondrial Disruption and Cell Death.

Journal of neuropathology and experimental neurology pii:5509469 [Epub ahead of print].

Mitochondrial Zn2+ accumulation, particularly in CA1 neurons, occurs after ischemia and likely contributes to mitochondrial dysfunction and subsequent neurodegeneration. However, the relationship between mitochondrial Zn2+ accumulation and their disruption has not been examined at the ultrastructural level in vivo. We employed a cardiac arrest model of transient global ischemia (TGI), combined with Timm's sulfide silver labeling, which inserts electron dense metallic silver granules at sites of labile Zn2+ accumulation, and used transmission electron microscopy (TEM) to examine subcellular loci of the Zn2+ accumulation. In line with prior studies, TGI-induced damage to CA1 was far greater than to CA3 pyramidal neurons, and was substantially progressive in the hours after reperfusion (being significantly greater after 4- than 1-hour recovery). Intriguingly, TEM examination of Timm's-stained sections revealed substantial Zn2+ accumulation in many postischemic CA1 mitochondria, which was strongly correlated with their swelling and disruption. Furthermore, paralleling the evolution of neuronal injury, both the number of mitochondria containing Zn2+ and the degree of their disruption were far greater at 4- than 1-hour recovery. These data provide the first direct characterization of Zn2+ accumulation in CA1 mitochondria after in vivo TGI, and support the idea that targeting these events could yield therapeutic benefits.

RevDate: 2019-05-29

de Oliveira Boldrini V, Farias ADS, GR Degasperi (2019)

Deciphering targets of Th17 cells fate: from metabolism to nuclear receptors.

Scandinavian journal of immunology [Epub ahead of print].

Evidence indicates that reprogramming of metabolism is critically important for the differentiation of CD4+ T lymphocytes, and the manipulation of metabolic pathways in these cells may shape their fate and function. Distinct subgroups from T lymphocytes, such as Th17, adopt specific metabolic programs to support their needs. Some important metabolic reactions, such as glycolysis, oxidative phosphorylation are considered important for the differentiation of these lymphocytes. Since their discovery nearly a decade ago, Th17 lymphocytes have received significant attention because of their role in the pathology of several immune-mediated inflammatory diseases such as Multiple Sclerosis. In this review, it will be discussed as the involvement of T cell metabolism and as metabolic reprogramming in activated T cells dictates fate decisions to Th17. The involvement of nuclear receptors such as RORyt e PPARs in the induction of Th17 cells was also discussed. Understanding the metabolic pathways involved in the differentiation of the distinct subgroups of T lymphocytes helps in the design of promising therapeutic proposals.

RevDate: 2019-05-29

Ghadery C, Best LA, Pavese N, et al (2019)

PET Evaluation of Microglial Activation in Non-neurodegenerative Brain Diseases.

Current neurology and neuroscience reports, 19(7):38 pii:10.1007/s11910-019-0951-x.

PURPOSE OF THE REVIEW: Microglial cell activation is an important component of neuroinflammation, and it is generally well accepted that chronic microglial activation is indicative of accumulating tissue damage in neurodegenerative conditions, particularly in the earlier stages of disease. Until recently, there has been less focus on the role of neuroinflammation in other forms of neurological and neuropsychiatric conditions. Through this review, we hope to demonstrate the important role TSPO PET imaging has played in illuminating the pivotal role of neuroinflammation and microglial activation underpinning these conditions.

RECENT FINDINGS: TSPO is an 18 kDa protein found on the outer membrane of mitochondria and can act as a marker of microglial activation using nuclear imaging. Through the development of radiopharmaceuticals targeting TSPO, researchers have been able to better characterise the spatial-temporal evolution of chronic neurological conditions, ranging from the focal autoimmune reactions seen in multiple sclerosis to the Wallerian degeneration at remote parts of the brain months following acute cerebral infarction. Development of novel techniques to investigate neuroinflammation within the central nervous system, for the purposes of diagnosis and therapeutics, has flourished over the past few decades. TSPO has proven itself a robust and sensitive biomarker of microglial activation and neuroimaging affords a minimally invasive technique to characterise neuroinflammatory processes in vivo.

RevDate: 2019-06-10

Storz JF, Cheviron ZA, McClelland GB, et al (2019)

Evolution of physiological performance capacities and environmental adaptation: insights from high-elevation deer mice (Peromyscus maniculatus).

Journal of mammalogy, 100(3):910-922.

Analysis of variation in whole-animal performance can shed light on causal connections between specific traits, integrated physiological capacities, and Darwinian fitness. Here, we review and synthesize information on naturally occurring variation in physiological performance capacities and how it relates to environmental adaptation in deer mice (Peromyscus maniculatus). We discuss how evolved changes in aerobic exercise capacity and thermogenic capacity have contributed to adaptation to high elevations. Comparative work on deer mice at high and low elevations has revealed evolved differences in aerobic performance capacities in hypoxia. Highland deer mice have consistently higher aerobic performance capacities under hypoxia relative to lowland natives, consistent with the idea that it is beneficial to have a higher maximal metabolic rate (as measured by the maximal rate of O2 consumption, VO2max) in an environment characterized by lower air temperatures and lower O2 availability. Observed differences in aerobic performance capacities between highland and lowland deer mice stem from changes in numerous subordinate traits that alter the flux capacity of the O2-transport system, the oxidative capacity of tissue mitochondria, and the relationship between O2 consumption and ATP synthesis. Many such changes in physiological phenotype are associated with hypoxia-induced changes in gene expression. Research on natural variation in whole-animal performance forms a nexus between physiological ecology and evolutionary biology that requires insight into the natural history of the study species.

RevDate: 2019-05-20

Dumesic PA, Egan DF, Gut P, et al (2019)

An Evolutionarily Conserved uORF Regulates PGC1α and Oxidative Metabolism in Mice, Flies, and Bluefin Tuna.

Cell metabolism pii:S1550-4131(19)30197-4 [Epub ahead of print].

Mitochondrial abundance and function are tightly controlled during metabolic adaptation but dysregulated in pathological states such as diabetes, neurodegeneration, cancer, and kidney disease. We show here that translation of PGC1α, a key governor of mitochondrial biogenesis and oxidative metabolism, is negatively regulated by an upstream open reading frame (uORF) in the 5' untranslated region of its gene (PPARGC1A). We find that uORF-mediated translational repression is a feature of PPARGC1A orthologs from human to fly. Strikingly, whereas multiple inhibitory uORFs are broadly present in fish PPARGC1A orthologs, they are completely absent in the Atlantic bluefin tuna, an animal with exceptionally high mitochondrial content. In mice, an engineered mutation disrupting the PPARGC1A uORF increases PGC1α protein levels and oxidative metabolism and confers protection from acute kidney injury. These studies identify a translational regulatory element governing oxidative metabolism and highlight its potential contribution to the evolution of organismal mitochondrial function.

RevDate: 2019-05-16

Tian R, Seim I, Ren W, et al (2019)

Contraction of the ROS Scavenging Enzyme Glutathione S-transferase Gene Family in Cetaceans.

G3 (Bethesda, Md.) pii:g3.119.400224 [Epub ahead of print].

Cetaceans are a group of marine mammals whose ancestors were adaptated for life on land. Life in an aquatic environment poses many challenges for air-breathing mammals. Diving marine mammals have adapted to rapid reoxygenation and reactive oxygen species (ROS)-mediated reperfusion injury. Here, we considered the evolution of the glutathione transferase (GST) gene family which has important roles in the detoxification of endogenously-derived ROS and environmental pollutants. We characterized the cytosolic GST gene family in 21 mammalian species; cetaceans, sirenians, pinnipeds, and their terrestrial relatives. All seven GST classes were identified, showing that GSTs are ubiquitous in mammals. Some GST genes are the product of lineage-specific duplications and losses, in line with a birth-and-death evolutionary model. We detected sites with signatures of positive selection that possibly influence GST structure and function, suggesting that adaptive evolution of GST genes is important for defending mammals from various types of noxious environmental compounds. We also found evidence for loss of alpha and mu GST subclass genes in cetacean lineages. Notably, cetaceans have retained a homolog of at least one of the genes GSTA1, GSTA4, and GSTM1; GSTs that are present in both the cytosol and mitochondria. The observed variation in number and selection pressure on GST genes suggest that the gene family structure is dynamic within cetaceans.

RevDate: 2019-05-15

Tan DX (2019)

Aging: An evolutionary competition between host cells and mitochondria.

Medical hypotheses, 127:120-128.

Here, a new theory of aging is proposed. This new theory is referred as the Host-Mitochondria Intracellular Innate Immune Theory of Aging (HMIIITA). The main point of this theory is that the aging is rooted from an evolutionary competition, that is, a never ending coevolutionary race between host cells and mitochondria. Mitochondria are the descendants of bacteria. The host cells will inevitably sense their bacterial origin, particularly their circular mtDNA. The host intracellular innate immune pressure (HIIIP) aims to eliminate mtDNA as more as possible while mitochondria have to adapt the HIIIP for survival. Co-evolution is required for both of them. From biological point of view, the larger, the mtDNA, the higher, the chance, it becomes the target of HIIIP. As a result, mitochondria have to reduce their mtDNA size via deletion. This process has last for 1.5-2 billion yeas and the result is that mitochondria have lost excessive 95% of their DNA. This mtDNA deletion is not associated with free radical attack but a unique trait acquired during evolution. In the postmitotic cells, the deletion is passively selected by the mitochondrial fission-fusion cycles. Eventually, the accumulation of deletion will significantly jeopardize the mitochondrial function. The dysfunctional mitochondria no longer provide sufficient ATP to support host cells' continuous demanding for growth. At this stage, the cell or the organism aging is inevitable.

RevDate: 2019-05-22

Shah A, Hoffman JI, H Schielzeth (2019)

Transcriptome assembly for a colour-polymorphic grasshopper (Gomphocerus sibiricus) with a very large genome size.

BMC genomics, 20(1):370 pii:10.1186/s12864-019-5756-4.

BACKGROUND: The club-legged grasshopper Gomphocerus sibiricus is a Gomphocerinae grasshopper with a promising future as model species for studying the maintenance of colour-polymorphism, the genetics of sexual ornamentation and genome size evolution. However, limited molecular resources are available for this species. Here, we present a de novo transcriptome assembly as reference resource for gene expression studies. We used high-throughput Illumina sequencing to generate 5,070,036 paired-end reads after quality filtering. We then combined the best-assembled contigs from three different de novo transcriptome assemblers (Trinity, SOAPdenovo-trans and Oases/Velvet) into a single assembly.

RESULTS: This resulted in 82,251 contigs with a N50 of 1357 and a TransRate assembly score of 0.325, which compares favourably with other orthopteran transcriptome assemblies. Around 87% of the transcripts could be annotated using InterProScan 5, BLASTx and the dammit! annotation pipeline. We identified a number of genes involved in pigmentation and green pigment metabolism pathways. Furthermore, we identified 76,221 putative single nucleotide polymorphisms residing in 8400 contigs. We also assembled the mitochondrial genome and investigated levels of sequence divergence with other species from the genus Gomphocerus. Finally, we detected and assembled Wolbachia sequences, which revealed close sequence similarity to the strain pel wPip.

CONCLUSIONS: Our study has generated a significant resource for uncovering genotype-phenotype associations in a species with an extraordinarily large genome, while also providing mitochondrial and Wolbachia sequences that will be useful for comparative studies.

RevDate: 2019-05-11

Brunk CF, WF Martin (2019)

Archaeal Histone Contributions to the Origin of Eukaryotes.

Trends in microbiology pii:S0966-842X(19)30095-2 [Epub ahead of print].

The eukaryotic lineage arose from bacterial and archaeal cells that underwent a symbiotic merger. At the origin of the eukaryote lineage, the bacterial partner contributed genes, metabolic energy, and the building blocks of the endomembrane system. What did the archaeal partner donate that made the eukaryotic experiment a success? The archaeal partner provided the potential for complex information processing. Archaeal histones were crucial in that regard by providing the basic functional unit with which eukaryotes organize DNA into nucleosomes, exert epigenetic control of gene expression, transcribe genes with CCAAT-box promoters, and a manifest cell cycle with condensed chromosomes. While mitochondrial energy lifted energetic constraints on eukaryotic protein production, histone-based chromatin organization paved the path to eukaryotic genome complexity, a critical hurdle en route to the evolution of complex cells.

RevDate: 2019-05-31

Castelli M, Sabaneyeva E, Lanzoni O, et al (2019)

Deianiraea, an extracellular bacterium associated with the ciliate Paramecium, suggests an alternative scenario for the evolution of Rickettsiales.

The ISME journal pii:10.1038/s41396-019-0433-9 [Epub ahead of print].

Rickettsiales are a lineage of obligate intracellular Alphaproteobacteria, encompassing important human pathogens, manipulators of host reproduction, and mutualists. Here we report the discovery of a novel Rickettsiales bacterium associated with Paramecium, displaying a unique extracellular lifestyle, including the ability to replicate outside host cells. Genomic analyses show that the bacterium possesses a higher capability to synthesise amino acids, compared to all investigated Rickettsiales. Considering these observations, phylogenetic and phylogenomic reconstructions, and re-evaluating the different means of interaction of Rickettsiales bacteria with eukaryotic cells, we propose an alternative scenario for the evolution of intracellularity in Rickettsiales. According to our reconstruction, the Rickettsiales ancestor would have been an extracellular and metabolically versatile bacterium, while obligate intracellularity would have evolved later, in parallel and independently, in different sub-lineages. The proposed new scenario could impact on the open debate on the lifestyle of the last common ancestor of mitochondria within Alphaproteobacteria.

RevDate: 2019-05-18

Bertolini MS, Chiurillo MA, Lander N, et al (2019)

MICU1 and MICU2 Play an Essential Role in Mitochondrial Ca2+ Uptake, Growth, and Infectivity of the Human Pathogen Trypanosoma cruzi.

mBio, 10(3): pii:mBio.00348-19.

The mitochondrial Ca2+ uptake in trypanosomatids, which belong to the eukaryotic supergroup Excavata, shares biochemical characteristics with that of animals, which, together with fungi, belong to the supergroup Opisthokonta. However, the composition of the mitochondrial calcium uniporter (MCU) complex in trypanosomatids is quite peculiar, suggesting lineage-specific adaptations. In this work, we used Trypanosoma cruzi to study the role of orthologs for mitochondrial calcium uptake 1 (MICU1) and MICU2 in mitochondrial Ca2+ uptake. T. cruzi MICU1 (TcMICU1) and TcMICU2 have mitochondrial targeting signals, two canonical EF-hand calcium-binding domains, and localize to the mitochondria. Using the CRISPR/Cas9 system (i.e., clustered regularly interspaced short palindromic repeats with Cas9), we generated TcMICU1 and TcMICU2 knockout (-KO) cell lines. Ablation of either TcMICU1 or TcMICU2 showed a significantly reduced mitochondrial Ca2+ uptake in permeabilized epimastigotes without dissipation of the mitochondrial membrane potential or effects on the AMP/ATP ratio or citrate synthase activity. However, none of these proteins had a gatekeeper function at low cytosolic Ca2+ concentrations ([Ca2+]cyt), as occurs with their mammalian orthologs. TcMICU1-KO and TcMICU2-KO epimastigotes had a lower growth rate and impaired oxidative metabolism, while infective trypomastigotes have a reduced capacity to invade host cells and to replicate within them as amastigotes. The findings of this work, which is the first to study the role of MICU1 and MICU2 in organisms evolutionarily distant from animals, suggest that, although these components were probably present in the last eukaryotic common ancestor (LECA), they developed different roles during evolution of different eukaryotic supergroups. The work also provides new insights into the adaptations of trypanosomatids to their particular life styles.IMPORTANCETrypanosoma cruzi is the etiologic agent of Chagas disease and belongs to the early-branching eukaryotic supergroup Excavata. Its mitochondrial calcium uniporter (MCU) subunit shares similarity with the animal ortholog that was important to discover its encoding gene. In animal cells, the MICU1 and MICU2 proteins act as Ca2+ sensors and gatekeepers of the MCU, preventing Ca2+ uptake under resting conditions and favoring it at high cytosolic Ca2+ concentrations ([Ca2+]cyt). Using the CRISPR/Cas9 technique, we generated TcMICU1 and TcMICU2 knockout cell lines and showed that MICU1 and -2 do not act as gatekeepers at low [Ca2+]cyt but are essential for normal growth, host cell invasion, and intracellular replication, revealing lineage-specific adaptations.

RevDate: 2019-05-08

Zhao D, Yu Y, Shen Y, et al (2019)

Melatonin Synthesis and Function: Evolutionary History in Animals and Plants.

Frontiers in endocrinology, 10:249.

Melatonin is an ancient molecule that can be traced back to the origin of life. Melatonin's initial function was likely that as a free radical scavenger. Melatonin presumably evolved in bacteria; it has been measured in both α-proteobacteria and in photosynthetic cyanobacteria. In early evolution, bacteria were phagocytosed by primitive eukaryotes for their nutrient value. According to the endosymbiotic theory, the ingested bacteria eventually developed a symbiotic association with their host eukaryotes. The ingested α-proteobacteria evolved into mitochondria while cyanobacteria became chloroplasts and both organelles retained their ability to produce melatonin. Since these organelles have persisted to the present day, all species that ever existed or currently exist may have or may continue to synthesize melatonin in their mitochondria (animals and plants) and chloroplasts (plants) where it functions as an antioxidant. Melatonin's other functions, including its multiple receptors, developed later in evolution. In present day animals, via receptor-mediated means, melatonin functions in the regulation of sleep, modulation of circadian rhythms, enhancement of immunity, as a multifunctional oncostatic agent, etc., while retaining its ability to reduce oxidative stress by processes that are, in part, receptor-independent. In plants, melatonin continues to function in reducing oxidative stress as well as in promoting seed germination and growth, improving stress resistance, stimulating the immune system and modulating circadian rhythms; a single melatonin receptor has been identified in land plants where it controls stomatal closure on leaves. The melatonin synthetic pathway varies somewhat between plants and animals. The amino acid, tryptophan, is the necessary precursor of melatonin in all taxa. In animals, tryptophan is initially hydroxylated to 5-hydroxytryptophan which is then decarboxylated with the formation of serotonin. Serotonin is either acetylated to N-acetylserotonin or it is methylated to form 5-methoxytryptamine; these products are either methylated or acetylated, respectively, to produce melatonin. In plants, tryptophan is first decarboxylated to tryptamine which is then hydroxylated to form serotonin.

RevDate: 2019-05-02

Nagarajan-Radha V, Rapkin J, Hunt J, et al (2019)

Interactions between mitochondrial haplotype and dietary macronutrient ratios confer sex-specific effects on longevity in Drosophila melanogaster.

The journals of gerontology. Series A, Biological sciences and medical sciences pii:5482495 [Epub ahead of print].

Recent studies have demonstrated that modifications to the ratio of dietary macronutrients affect longevity in a diverse range of species. However, the degree to which levels of natural genotypic variation shape these dietary effects on longevity remains unclear. The mitochondria have long been linked to the ageing process. The mitochondria possess their own genome, and previous studies have shown that mitochondrial genetic variation affects longevity in insects. Furthermore, the mitochondria are the sites in which dietary nutrients are oxidized to produce adenosine triphosphate, suggesting a capacity for dietary quality to mediate the link between mitochondrial genotype and longevity. Here, we measured longevity of male and female fruit flies, across a panel of genetic strains of Drosophila melanogaster, which vary only in their mitochondrial haplotype, when fed one of two isocaloric diets that differed in their protein-to-carbohydrate ratio. The mitochondrial haplotype affected the longevity of flies, but the pattern of these effects differed across the two diets in males, but not in females. We discuss the implications of these results in relation to an evolutionary theory linking maternal inheritance of mitochondria to the accumulation of male-harming mitochondrial mutations, and to the theory exploring the evolution of phenotypic plasticity to novel environments.

RevDate: 2019-05-01

John U, Lu Y, Wohlrab S, et al (2019)

An aerobic eukaryotic parasite with functional mitochondria that likely lacks a mitochondrial genome.

Science advances, 5(4):eaav1110 pii:aav1110.

Dinoflagellates are microbial eukaryotes that have exceptionally large nuclear genomes; however, their organelle genomes are small and fragmented and contain fewer genes than those of other eukaryotes. The genus Amoebophrya (Syndiniales) comprises endoparasites with high genetic diversity that can infect other dinoflagellates, such as those forming harmful algal blooms (e.g., Alexandrium). We sequenced the genome (~100 Mb) of Amoebophrya ceratii to investigate the early evolution of genomic characters in dinoflagellates. The A. ceratii genome encodes almost all essential biosynthetic pathways for self-sustaining cellular metabolism, suggesting a limited dependency on its host. Although dinoflagellates are thought to have descended from a photosynthetic ancestor, A. ceratii appears to have completely lost its plastid and nearly all genes of plastid origin. Functional mitochondria persist in all life stages of A. ceratii, but we found no evidence for the presence of a mitochondrial genome. Instead, all mitochondrial proteins appear to be lost or encoded in the A. ceratii nucleus.

RevDate: 2019-04-26

Pogoda CS, Keepers KG, Nadiadi AY, et al (2019)

Genome streamlining via complete loss of introns has occurred multiple times in lichenized fungal mitochondria.

Ecology and evolution, 9(7):4245-4263 pii:ECE35056.

Reductions in genome size and complexity are a hallmark of obligate symbioses. The mitochondrial genome displays clear examples of these reductions, with the ancestral alpha-proteobacterial genome size and gene number having been reduced by orders of magnitude in most descendent modern mitochondrial genomes. Here, we examine patterns of mitochondrial evolution specifically looking at intron size, number, and position across 58 species from 21 genera of lichenized Ascomycete fungi, representing a broad range of fungal diversity and niches. Our results show that the cox1gene always contained the highest number of introns out of all the mitochondrial protein-coding genes, that high intron sequence similarity (>90%) can be maintained between different genera, and that lichens have undergone at least two instances of complete, genome-wide intron loss consistent with evidence for genome streamlining via loss of parasitic, noncoding DNA, in Phlyctis boliviensisand Graphis lineola. Notably, however, lichenized fungi have not only undergone intron loss but in some instances have expanded considerably in size due to intron proliferation (e.g., Alectoria fallacina and Parmotrema neotropicum), even between closely related sister species (e.g., Cladonia). These results shed light on the highly dynamic mitochondrial evolution that is occurring in lichens and suggest that these obligate symbiotic organisms are in some cases undergoing recent, broad-scale genome streamlining via loss of protein-coding genes as well as noncoding, parasitic DNA elements.

RevDate: 2019-04-23

Titov VN, Sazhina NN, NМ Evteeva (2019)

[Ozone oxidizes oleic fatty acid with the highest rate constant and does not oxidize palmitic acid. Different physicochemical parameters of substrates and their role in phylogenesis.].

Klinicheskaia laboratornaia diagnostika, 64(3):132-139.

Physicochemical differences between О3 oxidation parameters for palmitic and oleic fatty acids (FA) during phylogenesis (evolution) are fundamental for а) production of palmitoleic monounsaturated fatty (MFA), b) formation of carnitine palmitoyltransferase as a FA transporter to mitochondria, and c) in vivo production of oleic MFA under humoral regulatory effect of insulin. In the strive for the best kinetic parameters of biological organisms without a possibility of modifying physicochemical and biochemical reactions in the mitochondrial matrix, the mitochondria can be provided with a substrate that increases energy production efficiency and the amount of ATP. Physicochemical parameters of oleic MFA has become the standard of an oxidation substrate for in vivo energy production; this MFA was synthesized in organisms for millions of years. Environmental influences are the second factor which determines kinetic perfection of biological organisms during phylogenesis. Are these influences always beneficial? Mostly, they are not. However, they largely stimulate adaptive functions of the organism, including the biological function of locomotion, cognitive function and the function of positioning in the environment. Biological, energy and kinetic perfection formed in vivo can be easily destroyed if phylogenetically herbivorous Homo sapiens abuses the diet of carnivorous animals (meat) which was not consumed by him and his ancestors during phylogenesis. This abuse is the major cause of metabolic pandemias in human population. They are: insulin resistance, atherosclerosis and atheromatosis, obesity and nonalcoholic liver disease. The most effective measures preventing metabolic pandemias, cardiac heart disease and myocardial infarction are extremely simple. People should remain herbivorous.

RevDate: 2019-04-23

Hsu J, Reilly A, Hayes BJ, et al (2019)

Reprogramming identifies functionally distinct stages of clonal evolution in myelodysplastic syndromes.

Blood pii:blood.2018884338 [Epub ahead of print].

Myeloid neoplasms, including myelodysplastic syndromes (MDS), are genetically heterogeneous disorders driven by clonal acquisition of somatic mutations in hematopoietic stem and progenitor cells (HPCs). The order of premalignant mutations and their impact on HPC self-renewal and differentiation remain poorly understood. We demonstrate that episomal reprogramming of MDS patient samples generates induced pluripotent stem cells (iPSCs) from single premalignant cells with a partial complement of mutations, directly informing the temporal order of mutations in the individual patient. Reprogramming preferentially captured early subclones with fewer mutations, which were rare among single patient cells. To evaluate the functional impact of clonal evolution in individual patients, we differentiated isogenic MDS-iPSCs harboring up to four successive clonal abnormalities recapitulating a progressive decrease in hematopoietic differentiation potential. SF3B1, in concert with epigenetic mutations, perturbed mitochondrial function leading to accumulation of damaged mitochondria during disease progression, resulting in apoptosis and ineffective erythropoiesis. Reprogramming also informed the order of premalignant mutations in patients with complex karyotype, and identified 5q deletion [del(5q)] as an early cytogenetic anomaly. Del(5q) cooperated with TP53 mutations to regulate genome stability promoting acquisition of structural and karyotypic abnormalities. Reprogramming thus enables molecular and functional interrogation of preleukemic clonal evolution, identifying mitochondrial function and chromosome stability as key pathways impacted by acquisition of somatic mutations in MDS.

RevDate: 2019-04-20

Tobler M, Barts N, R Greenway (2019)

Mitochondria and the origin of species: bridging genetic and ecological perspectives on speciation processes.

Integrative and comparative biology pii:5475603 [Epub ahead of print].

Mitochondria have been known to be involved in speciation through the generation of Dobzhansky-Muller incompatibilities, where functionally neutral co-evolution between mitochondrial and nuclear genomes can cause dysfunction when alleles are recombined in hybrids. We propose that adaptive mitochondrial divergence between populations can not only produce intrinsic (Dobzhansky-Muller) incompatibilities, but could also contribute to reproductive isolation through natural and sexual selection against migrants, post-mating prezygotic isolation, as well as by causing extrinsic reductions in hybrid fitness. We describe how these reproductive isolating barriers can potentially arise through adaptive divergence of mitochondrial function in the absence of mito-nuclear coevolution, a departure from more established views. While a role for mitochondria in the speciation process appears promising, we also highlight critical gaps of knowledge: (1) many systems with a potential for mitochondrially-mediated reproductive isolation lack crucial evidence directly linking reproductive isolation and mitochondrial function; (2) it often remains to be seen if mitochondrial barriers are a driver or a consequence of reproductive isolation; (3) the presence of substantial gene flow in the presence of mito-nuclear incompatibilities raises questions whether such incompatibilities are strong enough to drive speciation to completion; and (4) it remains to be tested how mitochondrial effects on reproductive isolation compare when multiple mechanisms of reproductive isolation coincide. We hope this perspective and the proposed research plans help to inform future studies of mitochondrial adaptation in a manner that links genotypic changes to phenotypic adaptations, fitness, and reproductive isolation in natural systems, helping to clarify the importance of mitochondria in the formation and maintenance of biological diversity.

RevDate: 2019-06-10

Meany MK, Conner WR, Richter SV, et al (2019)

Loss of cytoplasmic incompatibility and minimal fecundity effects explain relatively low Wolbachia frequencies in Drosophila mauritiana.

Evolution; international journal of organic evolution, 73(6):1278-1295.

Maternally transmitted Wolbachia bacteria infect about half of all insect species. Many Wolbachia cause cytoplasmic incompatibility (CI) and reduced egg hatch when uninfected females mate with infected males. Although CI produces a frequency-dependent fitness advantage that leads to high equilibrium Wolbachia frequencies, it does not aid Wolbachia spread from low frequencies. Indeed, the fitness advantages that produce initial Wolbachia spread and maintain non-CI Wolbachia remain elusive. wMau Wolbachia infecting Drosophila mauritiana do not cause CI, despite being very similar to CI-causing wNo from Drosophila simulans (0.068% sequence divergence over 682,494 bp), suggesting recent CI loss. Using draft wMau genomes, we identify a deletion in a CI-associated gene, consistent with theory predicting that selection within host lineages does not act to increase or maintain CI. In the laboratory, wMau shows near-perfect maternal transmission; but we find no significant effect on host fecundity, in contrast to published data. Intermediate wMau frequencies on the island of Mauritius are consistent with a balance between unidentified small, positive fitness effects and imperfect maternal transmission. Our phylogenomic analyses suggest that group-B Wolbachia, including wMau and wPip, diverged from group-A Wolbachia, such as wMel and wRi, 6-46 million years ago, more recently than previously estimated.

RevDate: 2019-06-10

Nibert ML, Debat HJ, Manny AR, et al (2019)

Mitovirus and Mitochondrial Coding Sequences from Basal Fungus Entomophthora muscae.

Viruses, 11(4): pii:v11040351.

Fungi constituting the Entomophthora muscae species complex (members of subphylum Entomophthoromycotina, phylum Zoopagamycota) commonly kill their insect hosts and manipulate host behaviors in the process. In this study, we made use of public transcriptome data to identify and characterize eight new species of mitoviruses associated with several different E. muscae isolates. Mitoviruses are simple RNA viruses that replicate in host mitochondria and are frequently found in more phylogenetically apical fungi (members of subphylum Glomeromyoctina, phylum Mucoromycota, phylum Basidiomycota and phylum Ascomycota) as well as in plants. E. muscae is the first fungus from phylum Zoopagomycota, and thereby the most phylogenetically basal fungus, found to harbor mitoviruses to date. Multiple UGA (Trp) codons are found not only in each of the new mitovirus sequences from E. muscae but also in mitochondrial core-gene coding sequences newly assembled from E. muscae transcriptome data, suggesting that UGA (Trp) is not a rarely used codon in the mitochondria of this fungus. The presence of mitoviruses in these basal fungi has possible implications for the evolution of these viruses.

RevDate: 2019-04-21

Kanchan S, Sharma P, S Chowdhury (2019)

Evolution of endonuclease IV protein family: an in silico analysis.

3 Biotech, 9(5):168.

DNA repair is one of the key cellular events which balances between evolvability and integrity of the genome. Endonuclease IV enzymes are class II AP endonucleases under base excision repair pathway which act on abasic site and break the phosphodiester bond at the 5' side. The role and activity of endonuclease IV proteins vary among different organisms; even it is absent in higher eukaryotes. The evolution of this protein family was studied by analyzing all homologs of the endonuclease IV protein family through different in silico techniques including phylogenetic tree generation and model building. The sequence analysis revealed four consensus sequence motifs within the AP2EC domain which are functionally important and conserved throughout the evolution process. It was also observed that the species and endonuclease IV gene evolution shape up differently in most of the organisms. Presence of the mitochondria-targeted signal peptides in fungal species Saccharomyces and Coccidioides suggest a possible endosymbiotic transfer of endonuclease IV genes to lower eukaryotes. Evolutionary changes among various clades in the protein-based phylogenetic tree have been investigated by comparison of homology models which suggests the conservation of overall fold of endonuclease IV proteins except for few alterations in loop orientation in few clades.

RevDate: 2019-05-15

Johri P, Marinov GK, Doak TG, et al (2019)

Population Genetics of Paramecium Mitochondrial Genomes: Recombination, Mutation Spectrum, and Efficacy of Selection.

Genome biology and evolution, 11(5):1398-1416.

The evolution of mitochondrial genomes and their population-genetic environment among unicellular eukaryotes are understudied. Ciliate mitochondrial genomes exhibit a unique combination of characteristics, including a linear organization and the presence of multiple genes with no known function or detectable homologs in other eukaryotes. Here we study the variation of ciliate mitochondrial genomes both within and across 13 highly diverged Paramecium species, including multiple species from the P. aurelia species complex, with four outgroup species: P. caudatum, P. multimicronucleatum, and two strains that may represent novel related species. We observe extraordinary conservation of gene order and protein-coding content in Paramecium mitochondria across species. In contrast, significant differences are observed in tRNA content and copy number, which is highly conserved in species belonging to the P. aurelia complex but variable among and even within the other Paramecium species. There is an increase in GC content from ∼20% to ∼40% on the branch leading to the P. aurelia complex. Patterns of polymorphism in population-genomic data and mutation-accumulation experiments suggest that the increase in GC content is primarily due to changes in the mutation spectra in the P. aurelia species. Finally, we find no evidence of recombination in Paramecium mitochondria and find that the mitochondrial genome appears to experience either similar or stronger efficacy of purifying selection than the nucleus.

RevDate: 2019-04-10

Garcia LE, Zubko MK, Zubko EI, et al (2019)

Elucidating genomic patterns and recombination events in plant cybrid mitochondria.

Plant molecular biology pii:10.1007/s11103-019-00869-z [Epub ahead of print].

KEY MESSAGE: Cybrid plant mitochondria undergo homologous recombination, mainly BIR, keep a single allele for each gene, and maintain exclusive sequences of each parent and a single copy of the homologous regions. The maintenance of a dynamic equilibrium between the mitochondrial and nuclear genomes requires continuous communication and a high level of compatibility between them, so that alterations in one genetic compartment need adjustments in the other. The co-evolution of nuclear and mitochondrial genomes has been poorly studied, even though the consequences and effects of this interaction are highly relevant for human health, as well as for crop improvement programs and for genetic engineering. The mitochondria of plants represent an excellent system to understand the mechanisms of genomic rearrangements, chimeric gene formation, incompatibility between nucleus and cytoplasm, and horizontal gene transfer. We carried out detailed analyses of the mtDNA of a repeated cybrid between the solanaceae Nicotiana tabacum and Hyoscyamus niger. The mtDNA of the cybrid was intermediate between the size of the parental mtDNAs and the sum of them. Noticeably, most of the homologous sequences inherited from both parents were lost. In contrast, the majority of the sequences exclusive of a single parent were maintained. The mitochondrial gene content included a majority of N. tabacum derived genes, but also chimeric, two-parent derived, and H. niger-derived genes in a tobacco nuclear background. Any of these alterations in the gene content could be the cause of CMS in the cybrid. The parental mtDNAs interacted through 28 homologous recombination events and a single case of illegitimate recombination. Three main homologous recombination mechanisms were recognized in the cybrid mitochondria. Break induced replication (BIR) pathway was the most frequent. We propose that BIR could be one of the mechanisms responsible for the loss of the majority of the repeated regions derived from H. niger.

RevDate: 2019-04-10

Mays JN, Camacho-Villasana Y, Garcia-Villegas R, et al (2019)

The mitoribosome-specific protein mS38 is preferentially required for synthesis of cytochrome c oxidase subunits.

Nucleic acids research pii:5436776 [Epub ahead of print].

Message-specific translational regulation mechanisms shape the biogenesis of multimeric oxidative phosphorylation (OXPHOS) enzyme in mitochondria from the yeast Saccharomyces cerevisiae. These mechanisms, driven mainly by the action of mRNA-specific translational activators, help to coordinate synthesis of OXPHOS catalytic subunits by the mitoribosomes with both the import of their nucleus-encoded partners and their assembly to form the holocomplexes. However, little is known regarding the role that the mitoribosome itself may play in mRNA-specific translational regulation. Here, we show that the mitoribosome small subunit protein Cox24/mS38, known to be necessary for mitoribosome-specific intersubunit bridge formation and 15S rRNA H44 stabilization, is required for efficient mitoribogenesis. Consequently, mS38 is necessary to sustain the overall mitochondrial protein synthesis rate, despite an adaptive ∼2-fold increase in mitoribosome abundance in mS38-deleted cells. Additionally, the absence of mS38 preferentially disturbs translation initiation of COX1, COX2, and COX3 mRNAs, without affecting the levels of mRNA-specific translational activators. We propose that mS38 confers the mitochondrial ribosome an intrinsic capacity of translational regulation, probably acquired during evolution from bacterial ribosomes to facilitate the translation of mitochondrial mRNAs, which lack typical anti-Shine-Dalgarno sequences.

RevDate: 2019-06-10

Nelson ED, NV Grishin (2019)

How Often Do Protein Genes Navigate Valleys of Low Fitness?.

Genes, 10(4): pii:genes10040283.

To escape from local fitness peaks, a population must navigate across valleys of low fitness. How these transitions occur, and what role they play in adaptation, have been subjects of active interest in evolutionary genetics for almost a century. However, to our knowledge, this problem has never been addressed directly by considering the evolution of a gene, or group of genes, as a whole, including the complex effects of fitness interactions among multiple loci. Here, we use a precise model of protein fitness to compute the probability P (s , Δ t) that an allele, randomly sampled from a population at time t, has crossed a fitness valley of depth s during an interval t - Δ t , t in the immediate past. We study populations of model genes evolving under equilibrium conditions consistent with those in mammalian mitochondria. From this data, we estimate that genes encoding small protein motifs navigate fitness valleys of depth 2 N s ≳ 30 with probability P ≳ 0 . 1 on a time scale of human evolution, where N is the (mitochondrial) effective population size. The results are consistent with recent findings for Watson⁻Crick switching in mammalian mitochondrial tRNA molecules.

RevDate: 2019-06-10

Hirakawa Y, A Watanabe (2019)

Organellar DNA Polymerases in Complex Plastid-Bearing Algae.

Biomolecules, 9(4): pii:biom9040140.

DNA replication in plastids and mitochondria is generally regulated by nucleus-encoded proteins. In plants and red algae, a nucleus-encoded enzyme called POP (plant and protist organellar DNA polymerase) is involved in DNA replication in both organelles by virtue of its dual localization. POPs are family A DNA polymerases, which include bacterial DNA polymerase I (PolI). POP homologs have been found in a wide range of eukaryotes, including plants, algae, and non-photosynthetic protists. However, the phylogeny and subcellular localizations of POPs remain unclear in many algae, especially in secondary and tertiary plastid-bearing groups. In this study, we report that chlorarachniophytes possess two evolutionarily distinct POPs, and fluorescent protein-tagging experiments demonstrate that they are targeted to the secondary plastids and mitochondria, respectively. The timing of DNA replication is different between the two organelles in the chlorarachniophyte Bigelowiella natans, and this seems to be correlated to the transcription of respective POP genes. Dinoflagellates also carry two distinct POP genes, possibly for their plastids and mitochondria, whereas haptophytes and ochrophytes have only one. Therefore, unlike plants, some algal groups are likely to have evolved multiple DNA polymerases for various organelles. This study provides a new insight into the evolution of organellar DNA replication in complex plastid-bearing organisms.

RevDate: 2019-04-06

Duvvuri B, C Lood (2019)

Cell-Free DNA as a Biomarker in Autoimmune Rheumatic Diseases.

Frontiers in immunology, 10:502.

Endogenous DNA is primarily found intracellularly in nuclei and mitochondria. However, extracellular, cell-free (cf) DNA, has been observed in several pathological conditions, including autoimmune diseases, prompting the interest of developing cfDNA as a potential biomarker. There is an upsurge in studies considering cfDNA to stratify patients, monitor the treatment response and predict disease progression, thus evaluating the prognostic potential of cfDNA for autoimmune diseases. Since the discovery of elevated cfDNA levels in lupus patients in the 1960s, cfDNA research in autoimmune diseases has mainly focused on the overall quantification of cfDNA and the association with disease activity. However, with recent technological advancements, including genomic and methylomic sequencing, qualitative changes in cfDNA are being explored in autoimmune diseases, similar to the ones used in molecular profiling of cfDNA in cancer patients. Further, the intracellular origin, e.g., if derived from mitochondrial or nuclear source, as well as the complexing with carrier molecules, including LL-37 and HMGB1, has emerged as important factors to consider when analyzing the quality and inflammatory potential of cfDNA. The clinical relevance of cfDNA in autoimmune rheumatic diseases is strengthened by mechanistic insights into the biological processes that result in an enhanced release of DNA into the circulation during autoimmune and inflammatory conditions. Prior work have established an important role of accelerated apoptosis and impaired clearance in leakage of nucleic acids into the extracellular environment. Findings from more recent studies, including our own investigations, have demonstrated that NETosis, a neutrophil cell death process, can result in a selective extrusion of inflammatory mitochondrial DNA; a process which is enhanced in patients with lupus and rheumatoid arthritis. In this review, we will summarize the evolution of cfDNA, both nuclear and mitochondrial DNA, as biomarkers for autoimmune rheumatic diseases and discuss limitations, challenges and implications to establish cfDNA as a biomarker for clinical use. This review will also highlight recent advancements in mechanistic studies demonstrating mitochondrial DNA as a central component of cfDNA in autoimmune rheumatic diseases.

RevDate: 2019-04-06

Moelling K, F Broecker (2019)

Viruses and Evolution - Viruses First? A Personal Perspective.

Frontiers in microbiology, 10:523.

The discovery of exoplanets within putative habitable zones revolutionized astrobiology in recent years. It stimulated interest in the question about the origin of life and its evolution. Here, we discuss what the roles of viruses might have been at the beginning of life and during evolution. Viruses are the most abundant biological entities on Earth. They are present everywhere, in our surrounding, the oceans, the soil and in every living being. Retroviruses contributed to about half of our genomic sequences and to the evolution of the mammalian placenta. Contemporary viruses reflect evolution ranging from the RNA world to the DNA-protein world. How far back can we trace their contribution? Earliest replicating and evolving entities are the ribozymes or viroids fulfilling several criteria of life. RNA can perform many aspects of life and influences our gene expression until today. The simplest structures with non-protein-coding information may represent models of life built on structural, not genetic information. Viruses today are obligatory parasites depending on host cells. Examples of how an independent lifestyle might have been lost include mitochondria, chloroplasts, Rickettsia and others, which used to be autonomous bacteria and became intracellular parasites or endosymbionts, thereby losing most of their genes. Even in vitro the loss of genes can be recapitulated all the way from coding to non-coding RNA. Furthermore, the giant viruses may indicate that there is no sharp border between living and non-living entities but an evolutionary continuum. Here, it is discussed how viruses can lose and gain genes, and that they are essential drivers of evolution. This discussion may stimulate the thinking about viruses as early possible forms of life. Apart from our view "viruses first", there are others such as "proteins first" and "metabolism first."

RevDate: 2019-05-20

Lama S, Broda M, Abbas Z, et al (2019)

Neofunctionalization of Mitochondrial Proteins and Incorporation into Signaling Networks in Plants.

Molecular biology and evolution, 36(5):974-989.

Because of their symbiotic origin, many mitochondrial proteins are well conserved across eukaryotic kingdoms. It is however less obvious how specific lineages have obtained novel nuclear-encoded mitochondrial proteins. Here, we report a case of mitochondrial neofunctionalization in plants. Phylogenetic analysis of genes containing the Domain of Unknown Function 295 (DUF295) revealed that the domain likely originated in Angiosperms. The C-terminal DUF295 domain is usually accompanied by an N-terminal F-box domain, involved in ubiquitin ligation via binding with ASK1/SKP1-type proteins. Due to gene duplication, the gene family has expanded rapidly, with 94 DUF295-related genes in Arabidopsis thaliana alone. Two DUF295 family subgroups have uniquely evolved and quickly expanded within Brassicaceae. One of these subgroups has completely lost the F-box, but instead obtained strongly predicted mitochondrial targeting peptides. We show that several representatives of this DUF295 Organellar group are effectively targeted to plant mitochondria and chloroplasts. Furthermore, many DUF295 Organellar genes are induced by mitochondrial dysfunction, whereas F-Box DUF295 genes are not. In agreement, several Brassicaceae-specific DUF295 Organellar genes were incorporated in the evolutionary much older ANAC017-dependent mitochondrial retrograde signaling pathway. Finally, a representative set of DUF295 T-DNA insertion mutants was created. No obvious aberrant phenotypes during normal growth and mitochondrial dysfunction were observed, most likely due to the large extent of gene duplication and redundancy. Overall, this study provides insight into how novel mitochondrial proteins can be created via "intercompartmental" gene duplication events. Moreover, our analysis shows that these newly evolved genes can then be specifically integrated into relevant, pre-existing coexpression networks.

RevDate: 2019-04-04

Degli Esposti M, Mentel M, Martin W, et al (2019)

Oxygen Reductases in Alphaproteobacterial Genomes: Physiological Evolution From Low to High Oxygen Environments.

Frontiers in microbiology, 10:499.

Oxygen reducing terminal oxidases differ with respect to their subunit composition, heme groups, operon structure, and affinity for O2. Six families of terminal oxidases are currently recognized, all of which occur in alphaproteobacterial genomes, two of which are also present in mitochondria. Many alphaproteobacteria encode several different terminal oxidases, likely reflecting ecological versatility with respect to oxygen levels. Terminal oxidase evolution likely started with the advent of O2 roughly 2.4 billion years ago and terminal oxidases diversified in the Proterozoic, during which oxygen levels remained low, around the Pasteur point (ca. 2 μM O2). Among the alphaproteobacterial genomes surveyed, those from members of the Rhodospirillaceae reveal the greatest diversity in oxygen reductases. Some harbor all six terminal oxidase types, in addition to many soluble enzymes typical of anaerobic fermentations in mitochondria and hydrogenosomes of eukaryotes. Recent data have it that O2 levels increased to current values (21% v/v or ca. 250 μM) only about 430 million years ago. Ecological adaptation brought forth different lineages of alphaproteobacteria and different lineages of eukaryotes that have undergone evolutionary specialization to high oxygen, low oxygen, and anaerobic habitats. Some have remained facultative anaerobes that are able to generate ATP with or without the help of oxygen and represent physiological links to the ancient proteobacterial lineage at the origin of mitochondria and eukaryotes. Our analysis reveals that the genomes of alphaproteobacteria appear to retain signatures of ancient transitions in aerobic metabolism, findings that are relevant to mitochondrial evolution in eukaryotes as well.

RevDate: 2019-04-08

Zimorski V, Mentel M, Tielens AGM, et al (2019)

Energy metabolism in anaerobic eukaryotes and Earth's late oxygenation.

Free radical biology & medicine pii:S0891-5849(18)32400-6 [Epub ahead of print].

Eukaryotes arose about 1.6 billion years ago, at a time when oxygen levels were still very low on Earth, both in the atmosphere and in the ocean. According to newer geochemical data, oxygen rose to approximately its present atmospheric levels very late in evolution, perhaps as late as the origin of land plants (only about 450 million years ago). It is therefore natural that many lineages of eukaryotes harbor, and use, enzymes for oxygen-independent energy metabolism. This paper provides a concise overview of anaerobic energy metabolism in eukaryotes with a focus on anaerobic energy metabolism in mitochondria. We also address the widespread assumption that oxygen improves the overall energetic state of a cell. While it is true that ATP yield from glucose or amino acids is increased in the presence of oxygen, it is also true that the synthesis of biomass costs thirteen times more energy per cell in the presence of oxygen than in anoxic conditions. This is because in the reaction of cellular biomass with O2, the equilibrium lies very far on the side of CO2. The absence of oxygen offers energetic benefits of the same magnitude as the presence of oxygen. Anaerobic and low oxygen environments are ancient. During evolution, some eukaryotes have specialized to life in permanently oxic environments (life on land), other eukaryotes have remained specialized to low oxygen habitats. We suggest that the Km of mitochondrial cytochrome c oxidase of 0.1-10 μM for O2, which corresponds to about 0.04%-4% (avg. 0.4%) of present atmospheric O2 levels, reflects environmental O2 concentrations that existed at the time that the eukaryotes arose.

RevDate: 2019-04-23
CmpDate: 2019-04-23

Vays VB, Vangeli IM, Eldarov CM, et al (2019)

Mitochondria in Obliquely Striated Muscles of the Horsehair Worm Gordionus alpestris (Nematomorpha, Gordioidea) with Structural Organization Typical of Cells with Energy-Intensive Processes.

Biochemistry. Biokhimiia, 84(1):56-61.

The ultrastructure of mitochondria in the flattened circomyarian fibers of the horsehair worm Gordionus alpestris (Nemathelminthes) was examined. In contrast to the previously published data, we showed these mitochondria to be giant elongated organelles that densely fill the central cytoplasmic space of the ribbon-like muscle fibers. No fundamental differences were found in the ultrastructure of the muscle tissue mitochondria in actively moving free-living and parasitic G. alpestris worms. The functional significance of the observed ultrastructural organization of mitochondria is discussed in connection with the necessity for an extended mitochondrial membrane system for a uniform supply of active muscle tissue with energy.

RevDate: 2019-03-29

Sudianto E, SM Chaw (2019)

Two independent plastid accD transfers to the nuclear genome of Gnetum and other insights on acetyl-CoA carboxylase evolution in gymnosperms.

Genome biology and evolution pii:5423182 [Epub ahead of print].

Acetyl-CoA carboxylase (ACCase) is the key regulator of fatty acid biosynthesis. In most plants, ACCase exists in two locations (cytosol and plastids) and in two forms (homomeric and heteromeric). Heteromeric ACCase comprises four subunits, three of them (ACCA-C) are nuclear-encoded (nr) and the fourth (ACCD) is usually plastid-encoded. Homomeric ACCase is encoded by a single nr-gene (ACC). We investigated the ACCase gene evolution in gymnosperms by examining the transcriptomes of newly sequenced Gnetum ula, combined with 75 transcriptomes and 110 plastomes of other gymnosperms. AccD coding sequences are elongated through the insertion of repetitive DNA in four out of five cupressophyte families (except Sciadopityaceae) and were functionally transferred to the nucleus of gnetophytes and Sciadopitys. We discovered that, among the three genera of gnetophytes, only Gnetum has two copies of nr-accD. Furthermore, using protoplast transient expression assays, we experimentally verified that the nr-accD precursor proteins in Gnetum and Sciadopitys can be delivered to the plastids. Of the two nr-accD copies of Gnetum, one dually targets plastids and mitochondria, while the other potentially targets plastoglobuli. The distinct transit peptides, gene architectures, and flanking sequences between the two Gnetum accDs suggest they have independent origins. Our findings are the first account of two distinctly targeted nr-accDs of any green plants and the most comprehensive analyses of ACCase evolution in gymnosperms to date.

RevDate: 2019-05-08

Aizawa S, Brar G, H Tsukamoto (2019)

Cell Death and Liver Disease.

Gut and liver pii:gnl18486 [Epub ahead of print].

Cell death is now reclassified into several types based on the mechanisms and morphologic phenotype. Understanding of such classifications offers insights into the pathogenesis of liver disease, as well as diagnostic or therapeutic implications. Apoptosis is recognized relatively easily due to its unique morphology, but lytic cell death may occur in the form of accidental necrosis, mitochondria permeability transition-driven necrosis, necroptosis, pyroptosis, ferroptosis, and parthanatos. The cell may be engulfed by neighboring cells due to a loss of integrin signaling or cancer cell competition by entosis, a type of cell death. The classification also includes mechanistically termed cell death such as autophagy-dependent cell death and lysosome-dependent cell death. These different types of cell death may occur uniquely in certain liver diseases but may coexist in the evolution of the disease. They occur in parenchymal and nonparenchymal liver cells, as well as inflammatory cells, causing distinct pathologic consequences. This review briefly covers the recently revised classifications of cell death and discusses their relevance to liver diseases of different etiologies.

RevDate: 2019-03-26

Weaver RJ (2019)

Hypothesized evolutionary consequences of the alternative oxidase (AOX) in animal mitochondria.

Integrative and comparative biology pii:5420160 [Epub ahead of print].

The environment in which eukaryotes first evolved was drastically different from what they experience today, and one of the key limiting factors was the availability of oxygen for mitochondrial respiration. During the transition to a fully oxygenated Earth, other compounds such as sulfide posed a considerable constraint on using mitochondrial aerobic respiration for energy production. The ancestors of animals, and those that first evolved from the simpler eukaryotes have mitochondrial respiratory components that are absent from later-evolving animals. Specifically, mitochondria of most basal metazoans have a sulfide-resistant alternative oxidase (AOX), which provides a secondary oxidative pathway to the classical cytochrome pathway. In this essay, I argue that because of its resistance to sulfide, AOX respiration was critical to the evolution of animals by enabling oxidative metabolism under otherwise inhibitory conditions. I hypothesize that AOX allowed for metabolic flexibility during the stochastic oxygen environment of early Earth which shaped the evolution of basal metazoans. I briefly describe the known functions of AOX, with a particular focus on the decreased production of reactive oxygen species (ROS) during stress conditions. Then, I propose three evolutionary consequences of AOX-mediated protection from ROS observed in basal metazoans: 1) adaptation to stressful environments, 2) the persistence of facultative sexual reproduction, and 3) decreased mitochondrial DNA mutation rates. Recognizing the diversity of mitochondrial respiratory systems present in animals may help resolve the mechanisms involved in major evolutionary processes such as adaptation and speciation.

RevDate: 2019-03-26

Arocena M, Landeira M, Di Paolo A, et al (2019)

Using a variant of coverslip hypoxia to visualize tumor cell alterations at increasing distances from an oxygen source.

Journal of cellular physiology [Epub ahead of print].

Early stages in tumor development involve growth in confined spaces, where oxygen diffusion is limited and metabolic waste products accumulate. This hostile microenvironment imposes strong selective pressures on tumor cells, leading eventually to the survival and expansion of aggressive subclones that condition further tumor evolution. To model features of this microenvironment in vitro, a diffusional barrier can be introduced in the form of a coverslip placed on top of cells, a method termed coverslip hypoxia. Using a variant of this method, with larger volume between coverslip and cells and with oxygen diffusion occurring only through a small hole in the center of the coverslip, we have visualized alterations in LNCaP tumor cells as a function of their distance to the oxygen source at the center. We observed remarkable morphological changes in LNCaP cells as the distance from the center increases, with cells becoming highly spread, displaying dynamic membrane protrusions and occasionally adopting a migratory phenotype. Concomitantly, cells farther from the center displayed marked increases in the hypoxia marker hypoxyprobe, whereas extracellular pH decreased in the same direction. Cells with altered morphology displayed prominent increases in fibrillar actin, as well as swollen mitochondria with distorted cristae and accumulation of neutral lipid-containing intracellular vesicles. These results show that an in vitro microenvironment that models diffusional barriers encountered by tumors in situ can have profound effects on tumor cells. The coverslip hypoxia variant we describe can be used to characterize in vitro the response of tumor cells to environmental conditions that play crucial roles in early tumor development.

RevDate: 2019-03-25
CmpDate: 2019-03-25

Liu W, Liu Q, Zhang Z, et al (2019)

Three-dimensional super-resolution imaging of live whole cells using galvanometer-based structured illumination microscopy.

Optics express, 27(5):7237-7248.

Imaging and tracking three-dimensional (3D) nanoscale organizations and functions of live cells is essential for biological research but it remains challenging. Among different 3D super-resolution techniques, 3D structured illumination microscopy (SIM) has the intrinsic advantages for live-cell studies; it is based on wide-field imaging and does not require high light intensities or special fluorescent dyes to double 3D resolution. However, the 3D SIM system has developed relatively slowly, especially in live imaging. Here, we report a more flexible 3D SIM system based on two galvanometer sets conveniently controlling the structured illumination pattern's period and orientation, which is able to study dynamics of live whole cells with high speed. We demonstrate our microscope's capabilities with strong optical sectioning and lateral, axial, and volume temporal resolution of 104 nm, 320 nm and 4 s, respectively. We do this by imaging nanoparticle and microtubule organizations and mitochondria evolution. These characteristics enable our galvanometer-based 3D SIM system to broaden the accessible imaging content of SIM-family microscopes and further facilitate their applications in life sciences.

RevDate: 2019-05-21
CmpDate: 2019-05-21

Dorrell RG, Azuma T, Nomura M, et al (2019)

Principles of plastid reductive evolution illuminated by nonphotosynthetic chrysophytes.

Proceedings of the National Academy of Sciences of the United States of America, 116(14):6914-6923.

The division of life into producers and consumers is blurred by evolution. For example, eukaryotic phototrophs can lose the capacity to photosynthesize, although they may retain vestigial plastids that perform other essential cellular functions. Chrysophyte algae have undergone a particularly large number of photosynthesis losses. Here, we present a plastid genome sequence from a nonphotosynthetic chrysophyte, "Spumella" sp. NIES-1846, and show that it has retained a nearly identical set of plastid-encoded functions as apicomplexan parasites. Our transcriptomic analysis of 12 different photosynthetic and nonphotosynthetic chrysophyte lineages reveals remarkable convergence in the functions of these nonphotosynthetic plastids, along with informative lineage-specific retentions and losses. At one extreme, Cornospumella fuschlensis retains many photosynthesis-associated proteins, although it appears to have lost the reductive pentose phosphate pathway and most plastid amino acid metabolism pathways. At the other extreme, Paraphysomonas lacks plastid-targeted proteins associated with gene expression and all metabolic pathways that require plastid-encoded partners, indicating a complete loss of plastid DNA in this genus. Intriguingly, some of the nucleus-encoded proteins that once functioned in the expression of the Paraphysomonas plastid genome have been retained. These proteins were likely to have been dual targeted to the plastid and mitochondria of the chrysophyte ancestor, and are uniquely targeted to the mitochondria in Paraphysomonas Our comparative analyses provide insights into the process of functional reduction in nonphotosynthetic plastids.

RevDate: 2019-04-26

Le Vasseur M, Chen VC, Huang K, et al (2019)

Pannexin 2 Localizes at ER-Mitochondria Contact Sites.

Cancers, 11(3): pii:cancers11030343.

Endomembrane specialization allows functional compartmentalization but imposes physical constraints to information flow within the cell. However, the evolution of an endomembrane system was associated with the emergence of contact sites facilitating communication between membrane-bound organelles. Contact sites between the endoplasmic reticulum (ER) and mitochondria are highly conserved in terms of their morphological features but show surprising molecular diversity within and across eukaryote species. ER-mitochondria contact sites are thought to regulate key processes in oncogenesis but their molecular composition remains poorly characterized in mammalian cells. In this study, we investigate the localization of pannexin 2 (Panx2), a membrane channel protein showing tumor-suppressing properties in cancer cells. Using a combination of subcellular fractionation, particle tracking in live-cell, and immunogold electron microscopy, we show that Panx2 localizes at ER-mitochondria contact sites in mammalian cells and sensitizes cells to apoptotic stimuli.

RevDate: 2019-05-10
CmpDate: 2019-05-10

Wang W, Chen J, Liao B, et al (2019)

Identification and functional characterization of Histone-like DNA-binding protein in Nocardia seriolae (NsHLP) involved in cell apoptosis.

Journal of fish diseases, 42(5):657-666.

Nocardia seriolae, a facultative intracellular bacterium, is the main pathogen of fish nocardiosis. Bioinformatic analysis showed that the histone-like DNA-binding protein (HLP) gene of N. seriolae (nshlp) encoded a secreted protein and might target the mitochondria in the host cell. To further study the preliminary function of HLP in N. seriolae (NsHLP), the gene cloning, extracellular products identification, subcellular localization, overexpression and apoptosis detection assay were carried out in this study. Mass spectrometry analysis of the extracellular products from N. seriolae showed that NsHLP was a secreted protein. Subcellular localization of HLP-GFP fusion proteins mainly assembled in the nucleus, which indicated that the NsHLP was co-located with the nucleus rather than mitochondria in fathead minnow (FHM) cells. Notably, the expression of NsHLP had changed the distribution of mitochondria into lumps in the FHM cell. In addition, apoptotic features were found in the transfected FHM cells by overexpression of NsHLP. Quantitative assays of mitochondrial membrane potential value, caspase-3 activity and pro-apoptotic genes mRNA (Bad, Bid and Bax) expression level demonstrated that the cell apoptosis was induced in the transfected FHM cells. All the results presented in this study provided insight on the function of NsHLP, which suggested that it may participate in the cell apoptosis regulation and play an important role in the pathogenesis of N. seriolae.

RevDate: 2019-03-29

Oldenkott B, Yang Y, Lesch E, et al (2019)

Plant-type pentatricopeptide repeat proteins with a DYW domain drive C-to-U RNA editing in Escherichia coli.

Communications biology, 2:85 pii:328.

RNA editing converting cytidines into uridines is a hallmark of gene expression in land plant chloroplasts and mitochondria. Pentatricopeptide repeat (PPR) proteins have a key role in target recognition, but the functional editosome in the plant organelles has remained elusive. Here we show that individual Physcomitrella patens DYW-type PPR proteins alone can perform efficient C-to-U editing in Escherichia coli reproducing the moss mitochondrial editing. Single amino acid exchanges in the DYW domain abolish RNA editing, confirming it as the functional cytidine deaminase. The modification of RNA targets and the identification of numerous off-targets in the E. coli transcriptome reveal nucleotide identities critical for RNA recognition and cytidine conversion. The straightforward amenability of the new E. coli setup will accelerate future studies on RNA target recognition through PPRs, on the C-to-U editing deamination machinery and towards future establishment of transcript editing in other genetic systems.

RevDate: 2019-03-29

Telschow A, Gadau J, Werren JH, et al (2019)

Genetic Incompatibilities Between Mitochondria and Nuclear Genes: Effect on Gene Flow and Speciation.

Frontiers in genetics, 10:62.

The process of speciation is, according to the biological species concept, the reduction in gene flow between genetically diverging populations. Most of the previous theoretical studies analyzed the effect of nuclear genetic incompatibilities on gene flow. There is, however, an increasing number of empirical examples suggesting that cytoplasmically inherited genetic elements play an important role in speciation. Here, we present a theoretical analysis of mitochondrial driven speciation, in which genetic incompatibilities occur between mitochondrial haplotypes and nuclear alleles. Four population genetic models with mainland-island structure were analyzed that differ with respect to the type of incompatibility and the underlying genetics. Gene flow reduction was measured on selectively neutral alleles of an unlinked locus and quantified by the effective migration rate. Analytical formulae for the different scenarios were derived using the fitness graph method. For the models with haploid genetics, we found that mito-nuclear incompatibilities (MtNI) are as strong as nuclear-nuclear incompatibilities (NNI) in reducing gene flow at the unlinked locus, but only if males and females migrate in equal number. For models with diploid genetics, we found that MtNI reduce gene flow stronger than NNI when incompatibilities are recessive, but weaker when they are dominant. For both haploid and diploid MtNI, we found that gene flow reduction is stronger if females are the migrating sex, but weaker than NNI when males are the migrating sex. These results encourage further examination on the role of mitochondria on genetic divergence and speciation and point toward specific factors (e.g., migrating sex) that could be the focus of an empirical test.

RevDate: 2019-06-10

Han Y, Branon TC, Martell JD, et al (2019)

Directed Evolution of Split APEX2 Peroxidase.

ACS chemical biology, 14(4):619-635.

APEX is an engineered peroxidase that catalyzes the oxidation of a wide range of substrates, facilitating its use in a variety of applications from subcellular staining for electron microscopy to proximity biotinylation for spatial proteomics and transcriptomics. To further advance the capabilities of APEX, we used directed evolution to engineer a split APEX tool (sAPEX). A total of 20 rounds of fluorescence activated cell sorting (FACS)-based selections from yeast-displayed fragment libraries, using 3 different surface display configurations, produced a 200-amino-acid N-terminal fragment (with 9 mutations relative to APEX2) called "AP" and a 50-amino-acid C-terminal fragment called "EX". AP and EX fragments were each inactive on their own but were reconstituted to give peroxidase activity when driven together by a molecular interaction. We demonstrate sAPEX reconstitution in the mammalian cytosol, on engineered RNA motifs within a non-coding RNA scaffold, and at mitochondria-endoplasmic reticulum contact sites.

RevDate: 2019-05-20

Thairu MW, AK Hansen (2019)

It's a small, small world: unravelling the role and evolution of small RNAs in organelle and endosymbiont genomes.

FEMS microbiology letters, 366(5):.

Organelles and host-restricted bacterial symbionts are characterized by having highly reduced genomes that lack many key regulatory genes and elements. Thus, it has been hypothesized that the eukaryotic nuclear genome is primarily responsible for regulating these symbioses. However, with the discovery of organelle- and symbiont-expressed small RNAs (sRNAs) there is emerging evidence that these sRNAs may play a role in gene regulation as well. Here, we compare the diversity of organelle and bacterial symbiont sRNAs recently identified using genome-enabled '-omic' technologies and discuss their potential role in gene regulation. We also discuss how the genome architecture of small genomes may influence the evolution of these sRNAs and their potential function. Additionally, these new studies suggest that some sRNAs are conserved within organelle and symbiont taxa and respond to changes in the environment and/or their hosts. In summary, these results suggest that organelle and symbiont sRNAs may play a role in gene regulation in addition to nuclear-encoded host mechanisms.

RevDate: 2019-03-12

Matos I, Machado MP, Schartl M, et al (2019)

Allele-specific expression variation at different ploidy levels in Squalius alburnoides.

Scientific reports, 9(1):3688 pii:10.1038/s41598-019-40210-8.

Allopolyploid plants are long known to be subject to a homoeolog expression bias of varying degree. The same phenomenon was only much later suspected to occur also in animals based on studies of single selected genes in an allopolyploid vertebrate, the Iberian fish Squalius alburnoides. Consequently, this species became a good model for understanding the evolution of gene expression regulation in polyploid vertebrates. Here, we analyzed for the first time genome-wide allele-specific expression data from diploid and triploid hybrids of S. alburnoides and compared homoeolog expression profiles of adult livers and of juveniles. Co-expression of alleles from both parental genomic types was observed for the majority of genes, but with marked homoeolog expression bias, suggesting homoeolog specific reshaping of expression level patterns in hybrids. Complete silencing of one allele was also observed irrespective of ploidy level, but not transcriptome wide as previously speculated. Instead, it was found only in a restricted number of genes, particularly ones with functions related to mitochondria and ribosomes. This leads us to hypothesize that allelic silencing may be a way to overcome intergenomic gene expression interaction conflicts, and that homoeolog expression bias may be an important mechanism in the achievement of sustainable genomic interactions, mandatory to the success of allopolyploid systems, as in S. alburnoides.

RevDate: 2019-03-09

Dixit S, Henderson JC, JD Alfonzo (2019)

Multi-Substrate Specificity and the Evolutionary Basis for Interdependence in tRNA Editing and Methylation Enzymes.

Frontiers in genetics, 10:104.

Among tRNA modification enzymes there is a correlation between specificity for multiple tRNA substrates and heteromultimerization. In general, enzymes that modify a conserved residue in different tRNA sequences adopt a heterodimeric structure. Presumably, such changes in the oligomeric state of enzymes, to gain multi-substrate recognition, are driven by the need to accommodate and catalyze a particular reaction in different substrates while maintaining high specificity. This review focuses on two classes of enzymes where the case for multimerization as a way to diversify molecular recognition can be made. We will highlight several new themes with tRNA methyltransferases and will also discuss recent findings with tRNA editing deaminases. These topics will be discussed in the context of several mechanisms by which heterodimerization may have been achieved during evolution and how these mechanisms might impact modifications in different systems.

RevDate: 2019-03-18
CmpDate: 2019-03-18

Forgione I, Bonavita S, TMR Regina (2019)

Mitochondria of Cedrus atlantica and allied species: A new chapter in the horizontal gene transfer history.

Plant science : an international journal of experimental plant biology, 281:93-101.

The extraordinary incidence of Horizontal Gene Transfer (HGT) mostly in mitochondrial genomes of flowering plants is well known. Here, we report another episode of HGT affecting a large mitochondrial gene region in the evergreen conifer Atlas cedar (Cedrus atlantica). Mitochondria of this Pinaceae species possess an rps3 gene that harbours two introns and shares the same genomic context with a downstream overlapping rpl16 gene, like in the major groups of gymnosperms and angiosperms analyzed so far. Interestingly, C. atlantica contains additional copies of the rps3 and rpl16 sequences that are more closely related to angiosperm counterparts than to those from gymnosperms, as also confirmed by phylogenetic analyses. This suggests that a lateral transfer from a flowering plant donor is the most likely mechanism for the origin of the Atlas cedar extra sequences. Quantitative PCR and reverse-transcription (RT)-PCR analyses demonstrate, respectively, mitochondrial location and lack of expression for the rps3 and rpl16 additional sequences in C. atlantica. Furthermore, our study provides evidence that a similar HGT event takes place in two other Cedrus species, which occurr in Cyprus and North Africa. Only the West Himalayan C. deodara lacks the transferred genes. The potential donor and the molecular mechanism underlying this lateral DNA transfer remain still unclear.

RevDate: 2019-04-30

Meyer EH, Welchen E, C Carrie (2019)

Assembly of the Complexes of the Oxidative Phosphorylation System in Land Plant Mitochondria.

Annual review of plant biology, 70:23-50.

Plant mitochondria play a major role during respiration by producing the ATP required for metabolism and growth. ATP is produced during oxidative phosphorylation (OXPHOS), a metabolic pathway coupling electron transfer with ADP phosphorylation via the formation and release of a proton gradient across the inner mitochondrial membrane. The OXPHOS system is composed of large, multiprotein complexes coordinating metal-containing cofactors for the transfer of electrons. In this review, we summarize the current state of knowledge about assembly of the OXPHOS complexes in land plants. We present the different steps involved in the formation of functional complexes and the regulatory mechanisms controlling the assembly pathways. Because several assembly steps have been found to be ancestral in plants-compared with those described in fungal and animal models-we discuss the evolutionary dynamics that lead to the conservation of ancestral pathways in land plant mitochondria.

RevDate: 2019-05-23
CmpDate: 2019-05-23

Kuzminkova AA, Sokol AD, Ushakova KE, et al (2019)

mtProtEvol: the resource presenting molecular evolution analysis of proteins involved in the function of Vertebrate mitochondria.

BMC evolutionary biology, 19(Suppl 1):47 pii:10.1186/s12862-019-1371-x.

BACKGROUND: Heterotachy is the variation in the evolutionary rate of aligned sites in different parts of the phylogenetic tree. It occurs mainly due to epistatic interactions among the substitutions, which are highly complex and make it difficult to study protein evolution. The vast majority of computational evolutionary approaches for studying these epistatic interactions or their evolutionary consequences in proteins require high computational time. However, recently, it has been shown that the evolution of residue solvent accessibility (RSA) is tightly linked with changes in protein fitness and intra-protein epistatic interactions. This provides a computationally fast alternative, based on comparison of evolutionary rates of amino acid replacements with the rates of RSA evolutionary changes in order to recognize any shifts in epistatic interaction.

RESULTS: Based on RSA information, data randomization and phylogenetic approaches, we constructed a software pipeline, which can be used to analyze the evolutionary consequences of intra-protein epistatic interactions with relatively low computational time. We analyzed the evolution of 512 protein families tightly linked to mitochondrial function in Vertebrates and created "mtProtEvol", the web resource with data on protein evolution. In strict agreement with lifespan and metabolic rate data, we demonstrated that different functional categories of mitochondria-related proteins subjected to selection on accelerated and decelerated RSA rates in rodents and primates. For example, accelerated RSA evolution in rodents has been shown for Krebs cycle enzymes, respiratory chain and reactive oxygen species metabolism, while in primates these functions are stress-response, translation and mtDNA integrity. Decelerated RSA evolution in rodents has been demonstrated for translational machinery and oxidative stress response components.

CONCLUSIONS: mtProtEvol is an interactive resource focused on evolutionary analysis of epistatic interactions in protein families involved in Vertebrata mitochondria function and available at http://bioinfodbs.kantiana.ru/mtProtEvol /. This resource and the devised software pipeline may be useful tool for researchers in area of protein evolution.

RevDate: 2019-05-10

Tan Y, Zhu Y, Wen L, et al (2019)

Mitochondria-Responsive Drug Release along with Heat Shock Mediated by Multifunctional Glycolipid Micelles for Precise Cancer Chemo-Phototherapy.

Theranostics, 9(3):691-707 pii:thnov09p0691.

Responsive drug release in tumor mitochondria is a pre-requisite for mitochondria-targeted drug delivery systems to improve the efficacy of this promising therapeutic modality. To this end, a photothermal stimulation strategy for mitochondria-responsive drug release along with heat shock is developed to maximize the antitumor effects with minimal side effects. Methods: This strategy relies on mitochondrial-targeted delivery of doxorubicin (DOX) through a photothermal and lipophilic agent IR-780 iodide (IR780)-modified glycolipid conjugates (CSOSA), which can synergistically triggers high-level reactive oxygen species (ROS) to kill tumor cells. Results: Specifically, upon laser irradiation, the photothermal conversion by IR780-CSOSA can not only weaken the hydrophobic interaction between the core of micelles and DOX and trigger unexpected micelle swelling to release DOX in mitochondria for the amplification of ROS, but also induce mitochondria-specific heat shock to promote the fast evolution of ROS at the same locus to eradicate cancer cells in a more effective way. Furthermore, IR780-CSOSA micelles may independently realize the real-time diagnosis and imaging on multiple tumor models. Deep penetration into tumors by IR780-CSOSA/DOX micelles can be manipulated under laser irradiation. Conclusion: Such multifunctional IR780-CSOSA/DOX micelles with integration of mitochondria-responsive drug release and heat shock are demonstrated to be superior to the non-mitochondria-responsive therapy. This study opens up new avenues for the future cancer diagnosis and treatment.

RevDate: 2019-03-03

Hirata A (2019)

Recent Insights Into the Structure, Function, and Evolution of the RNA-Splicing Endonucleases.

Frontiers in genetics, 10:103.

RNA-splicing endonuclease (EndA) cleaves out introns from archaeal and eukaryotic precursor (pre)-tRNA and is essential for tRNA maturation. In archaeal EndA, the molecular mechanisms underlying complex assembly, substrate recognition, and catalysis have been well understood. Recently, certain studies have reported novel findings including the identification of new subunit types in archaeal EndA structures, providing insights into the mechanism underlying broad substrate specificity. Further, metagenomics analyses have enabled the acquisition of numerous DNA sequences of EndAs and intron-containing pre-tRNAs from various species, providing information regarding the co-evolution of substrate specificity of archaeal EndAs and tRNA genetic diversity, and the evolutionary pathway of archaeal and eukaryotic EndAs. Although the complex structure of the heterothermic form of eukaryotic EndAs is unknown, previous reports regarding their functions indicated that mutations in human EndA cause neurological disorders including pontocerebellar hypoplasia and progressive microcephaly, and yeast EndA significantly cleaves mitochondria-localized mRNA encoding cytochrome b mRNA processing 1 (Cpb1) for mRNA maturation. This mini-review summarizes the aforementioned results, discusses their implications, and offers my personal opinion regarding future directions for the analysis of the structure and function of EndAs.

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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.

ESP Rationale

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.

ESP Goal

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.

ESP Usage

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.

ESP Plans

With the development of methods for adding typeset side notes to PDF files, the ESP project now plans to add annotated versions of some classical papers to its holdings. We also plan to add new reference and pedagogical material. We have already started providing regularly updated, comprehensive bibliographies to the ESP.ORG site.

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Papers in Classical Genetics

The ESP began as an effort to share a handful of key papers from the early days of classical genetics. Now the collection has grown to include hundreds of papers, in full-text format.

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Along with papers on classical genetics, ESP offers a collection of full-text digital books, including many works by Darwin (and even a collection of poetry — Chicago Poems by Carl Sandburg).

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Selected Bibliographies

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