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Zoological Research Jan 2022In most eukaryotes, oxidative phosphorylation (OXPHOS) is the main energy production process and it involves both mitochondrial and nuclear genomes. The close...
In most eukaryotes, oxidative phosphorylation (OXPHOS) is the main energy production process and it involves both mitochondrial and nuclear genomes. The close interaction between the two genomes is critical for the coordinated function of the OXPHOS process. Some bivalves show doubly uniparental inheritance (DUI) of mitochondria, where two highly divergent mitochondrial genomes, one inherited through eggs (F-type) and the other through sperm (M-type), coexist in the same individual. However, it remains a puzzle how nuclear OXPHOS genes coordinate with two divergent mitochondrial genomes in DUI species. In this study, we compared transcription, polymorphism, and synonymous codon usage in the mitochondrial and nuclear OXPHOS genes of the DUI species using sex- and tissue-specific transcriptomes. Mitochondrial and nuclear OXPHOS genes showed different transcription profiles. Strong co-transcription signal was observed within mitochondrial (separate for F- and M-type) and within nuclear OXPHOS genes but the signal was weak or absent between mitochondrial and nuclear OXPHOS genes, suggesting that the coordination between mitochondrial and nuclear OXPHOS subunits is not achieved transcriptionally. McDonald-Kreitman and frequency-spectrum based tests indicated that M-type OXPHOS genes deviated significantly from neutrality, and that F-type and M-type OXPHOS genes undergo different selection patterns. Codon usage analysis revealed that mutation bias and translational selection were the major factors affecting the codon usage bias in different OXPHOS genes, nevertheless, translational selection in mitochondrial OXPHOS genes appears to be less efficient than nuclear OXPHOS genes. Therefore, we speculate that the coordination between OXPHOS genes may involve post-transcriptional/translational regulation.
Topics: Animals; Bivalvia; Genes, Mitochondrial; Genome, Mitochondrial; Mitochondria; Oxidative Phosphorylation
PubMed: 34904419
DOI: 10.24272/j.issn.2095-8137.2021.348 -
Proceedings of the National Academy of... Apr 2008Genes encoded by mitochondrial DNA (mtDNA) exist in large numbers per cell but can be selected very rapidly as a result of unequal partitioning of mtDNA between germ...
Genes encoded by mitochondrial DNA (mtDNA) exist in large numbers per cell but can be selected very rapidly as a result of unequal partitioning of mtDNA between germ cells during embryogenesis. However, empirical studies of this "bottlenecking" effect are rare because of the apparent scarcity of heteroplasmic individuals possessing more than one mtDNA haplotype. Here, we report an example of insecticide resistance in an arthropod pest (Tetranychus urticae) being controlled by mtDNA and on its inheritance in a heteroplasmic mite strain. Resistance to the insecticide bifenazate is highly correlated with remarkable mutations in cytochrome b, a mitochondrially encoded protein in the respiratory pathway. Four sites in the Q(o) site that are absolutely conserved across fungi, protozoa, plants, and animals are mutated in resistant mite strains. Despite the unusual nature of these mutations, resistant mites showed no fitness costs in the absence of insecticide. Partially resistant strains, consisting of heteroplasmic individuals, transmit their resistant and susceptible haplotypes to progeny in highly variable ratios consistent with a sampling bottleneck of approximately 180 copies. Insecticide selection on heteroplasmic individuals favors those carrying resistant haplotypes at a frequency of 60% or more. This combination of factors enables very rapid evolution and accounts for mutations being fixed in most field-collected resistant strains. The results provide a rare insight into non-Mendelian mechanisms of mitochondrial inheritance and evolution, relevant to anticipating and understanding the development of other mitochondrially encoded adaptations in arthropods. They also provide strong evidence of cytochrome b being the target site for bifenazate in spider mites.
Topics: Amino Acid Sequence; Animals; Base Sequence; Carbamates; Cytochromes b; DNA, Mitochondrial; Evolution, Molecular; Female; Genes, Mitochondrial; Genome, Mitochondrial; Hydrazines; Insecticide Resistance; Insecticides; Male; Molecular Sequence Data; Mutation; Tetranychidae
PubMed: 18408150
DOI: 10.1073/pnas.0802224105 -
Biological Psychiatry May 2018The genetic risk factors of schizophrenia (SCZ), a severe psychiatric disorder, are not yet fully understood. Multiple lines of evidence suggest that mitochondrial... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The genetic risk factors of schizophrenia (SCZ), a severe psychiatric disorder, are not yet fully understood. Multiple lines of evidence suggest that mitochondrial dysfunction may play a role in SCZ, but comprehensive association studies are lacking. We hypothesized that variants in nuclear-encoded mitochondrial genes influence susceptibility to SCZ.
METHODS
We conducted gene-based and gene-set analyses using summary association results from the Psychiatric Genomics Consortium Schizophrenia Phase 2 (PGC-SCZ2) genome-wide association study comprising 35,476 cases and 46,839 control subjects. We applied the MAGMA method to three sets of nuclear-encoded mitochondrial genes: oxidative phosphorylation genes, other nuclear-encoded mitochondrial genes, and genes involved in nucleus-mitochondria crosstalk. Furthermore, we conducted a replication study using the iPSYCH SCZ sample of 2290 cases and 21,621 control subjects.
RESULTS
In the PGC-SCZ2 sample, 1186 mitochondrial genes were analyzed, among which 159 had p values < .05 and 19 remained significant after multiple testing correction. A meta-analysis of 818 genes combining the PGC-SCZ2 and iPSYCH samples resulted in 104 nominally significant and nine significant genes, suggesting a polygenic model for the nuclear-encoded mitochondrial genes. Gene-set analysis, however, did not show significant results. In an in silico protein-protein interaction network analysis, 14 mitochondrial genes interacted directly with 158 SCZ risk genes identified in PGC-SCZ2 (permutation p = .02), and aldosterone signaling in epithelial cells and mitochondrial dysfunction pathways appeared to be overrepresented in this network of mitochondrial and SCZ risk genes.
CONCLUSIONS
This study provides evidence that specific aspects of mitochondrial function may play a role in SCZ, but we did not observe its broad involvement even using a large sample.
Topics: Adolescent; Adult; Aged; Female; Genes, Mitochondrial; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Male; Middle Aged; Schizophrenia; Young Adult
PubMed: 29628042
DOI: 10.1016/j.biopsych.2018.02.1175 -
Systematic Biology Aug 2023The mitochondrial genomes of Bilateria are relatively conserved in their protein-coding, rRNA, and tRNA gene complement, but the order of these genes can range from very...
The mitochondrial genomes of Bilateria are relatively conserved in their protein-coding, rRNA, and tRNA gene complement, but the order of these genes can range from very conserved to very variable depending on the taxon. The supposedly conserved gene order of Annelida has been used to support the placement of some taxa within Annelida. Recently, authors have cast doubts on the conserved nature of the annelid gene order. Various factors may influence gene order variability including, among others, increased substitution rates, base composition differences, structure of noncoding regions, parasitism, living in extreme habitats, short generation times, and biomineralization. However, these analyses were neither done systematically nor based on well-established reference trees. Several focused on only a few of these factors and biological factors were usually explored ad-hoc without rigorous testing or correlation analyses. Herein, we investigated the variability and evolution of the annelid gene order and the factors that potentially influenced its evolution, using a comprehensive and systematic approach. The analyses were based on 170 genomes, including 33 previously unrepresented species. Our analyses included 706 different molecular properties, 20 life-history and ecological traits, and a reference tree corresponding to recent improvements concerning the annelid tree. The results showed that the gene order with and without tRNAs is generally conserved. However, individual taxa exhibit higher degrees of variability. None of the analyzed life-history and ecological traits explained the observed variability across mitochondrial gene orders. In contrast, the combination and interaction of the best-predicting factors for substitution rate and base composition explained up to 30% of the observed variability. Accordingly, correlation analyses of different molecular properties of the mitochondrial genomes showed an intricate network of direct and indirect correlations between the different molecular factors. Hence, gene order evolution seems to be driven by molecular evolutionary aspects rather than by life history or ecology. On the other hand, variability of the gene order does not predict if a taxon is difficult to place in molecular phylogenetic reconstructions using sequence data or not. We also discuss the molecular properties of annelid mitochondrial genomes considering canonical views on gene evolution and potential reasons why the canonical views do not always fit to the observed patterns without making some adjustments. [Annelida; compositional biases; ecology; gene order; life history; macroevolution; mitochondrial genomes; substitution rates.].
Topics: Animals; Genome, Mitochondrial; Gene Order; Phylogeny; Annelida; Genes, Mitochondrial; Evolution, Molecular; DNA, Mitochondrial
PubMed: 37083277
DOI: 10.1093/sysbio/syad023 -
Mitochondrion Mar 2010Demyelination occurs in multiple inherited mitochondrial diseases. We studied which genes were induced as a consequence of differentiation in rodent and human...
Demyelination occurs in multiple inherited mitochondrial diseases. We studied which genes were induced as a consequence of differentiation in rodent and human oligodendroglia. Cholesterol, myelin and mitochondrial genes were significantly increased with oligodendroglial differentiation. Mitochondrial DNA content per cell and acetyl CoA-related transcripts increased significantly; thus, the large buildup of cholesterol necessary for myelination appears to require mitochondrial production of acetyl-CoA. Oligodendroglia were treated with low doses of the mitochondrial inhibitor rotenone to test the dependence of differentiation on mitochondrial function. Undifferentiated cells were resistant to rotenone, whereas differentiating cells were much more sensitive. Very low doses of rotenone that did not affect viability or ATP synthesis still inhibited differentiation, as measured by reduced levels of the myelin transcripts 2',3'-Cyclic Nucleotide-3'-Phosphodiesterase and Myelin Basic Protein. Thus, mitochondrial transcripts and mtDNA are amplified during oligodendroglial differentiation, and differentiating oligodendroglia are especially sensitive to mitochondrial inhibition, suggesting mechanisms for demyelination observed in mitochondrial disease.
Topics: Acetyl Coenzyme A; Cell Differentiation; Genes, Mitochondrial; Humans; Metabolic Networks and Pathways; Mitochondria; Oligodendroglia; Rotenone; Transcriptional Activation; Uncoupling Agents
PubMed: 20005986
DOI: 10.1016/j.mito.2009.12.141 -
Biochimica Et Biophysica Acta Jun 2011Warburg proposed that cancer originates from irreversible injury to mitochondrial oxidative phosphorylation (mtOXPHOS), which leads to an increase rate of aerobic... (Review)
Review
Warburg proposed that cancer originates from irreversible injury to mitochondrial oxidative phosphorylation (mtOXPHOS), which leads to an increase rate of aerobic glycolysis in most cancers. However, despite several decades of research related to Warburg effect, very little is known about the underlying genetic cause(s) of mtOXPHOS impairment in cancers. Proteins that participate in mtOXPHOS are encoded by both mitochondrial DNA (mtDNA) as well as nuclear DNA. This review describes mutations in mtDNA and reduced mtDNA copy number, which contribute to OXPHOS defects in cancer cells. Maternally inherited mtDNA renders susceptibility to cancer, and mutation in the nuclear encoded genes causes defects in mtOXPHOS system. Mitochondria damage checkpoint (mitocheckpoint) induces epigenomic changes in the nucleus, which can reverse injury to OXPHOS. However, irreversible injury to OXPHOS can lead to persistent mitochondrial dysfunction inducing genetic instability in the nuclear genome. Together, we propose that "mitocheckpoint" led epigenomic and genomic changes must play a key role in reversible and irreversible injury to OXPHOS described by Warburg. These epigenetic and genetic changes underlie the Warburg phenotype, which contributes to the development of cancer.
Topics: Animals; Cell Nucleus; Cell Transformation, Neoplastic; DNA, Mitochondrial; Genes, Mitochondrial; Humans; Mitochondrial Diseases; Models, Biological; Neoplasms; Oxidative Phosphorylation
PubMed: 21074512
DOI: 10.1016/j.bbabio.2010.10.023 -
Nature Communications Feb 2021DddA-derived cytosine base editors (DdCBEs), composed of the split interbacterial toxin DddA, transcription activator-like effector (TALE), and uracil glycosylase...
DddA-derived cytosine base editors (DdCBEs), composed of the split interbacterial toxin DddA, transcription activator-like effector (TALE), and uracil glycosylase inhibitor (UGI), enable targeted C-to-T base conversions in mitochondrial DNA (mtDNA). Here, we demonstrate highly efficient mtDNA editing in mouse embryos using custom-designed DdCBEs. We target the mitochondrial gene, MT-ND5 (ND5), which encodes a subunit of NADH dehydrogenase that catalyzes NADH dehydration and electron transfer to ubiquinone, to obtain several mtDNA mutations, including m.G12918A associated with human mitochondrial diseases and m.C12336T that incorporates a premature stop codon, creating mitochondrial disease models in mice and demonstrating a potential for the treatment of mitochondrial disorders.
Topics: Animals; DNA, Mitochondrial; Electron Transport; Female; Gene Editing; Genes, Mitochondrial; Male; Mice; Mice, Inbred C57BL; Mitochondria; Mitochondrial Diseases; Mitochondrial Proteins; Mutation; NADH Dehydrogenase; NIH 3T3 Cells; Transcription Activator-Like Effectors
PubMed: 33608520
DOI: 10.1038/s41467-021-21464-1 -
PloS One 2016Aspergillus flavus colonizes agricultural commodities worldwide and contaminates them with carcinogenic aflatoxins. The high genetic diversity of A. flavus populations...
Aspergillus flavus colonizes agricultural commodities worldwide and contaminates them with carcinogenic aflatoxins. The high genetic diversity of A. flavus populations is largely due to sexual reproduction characterized by the formation of ascospore-bearing ascocarps embedded within sclerotia. A. flavus is heterothallic and laboratory crosses between strains of the opposite mating type produce progeny showing genetic recombination. Sclerotia formed in crops are dispersed onto the soil surface at harvest and are predominantly produced by single strains of one mating type. Less commonly, sclerotia may be fertilized during co-infection of crops with sexually compatible strains. In this study, laboratory and field experiments were performed to examine sexual reproduction in single-strain and fertilized sclerotia following exposure of sclerotia to natural fungal populations in soil. Female and male roles and mitochondrial inheritance in A. flavus were also examined through reciprocal crosses between sclerotia and conidia. Single-strain sclerotia produced ascospores on soil and progeny showed biparental inheritance that included novel alleles originating from fertilization by native soil strains. Sclerotia fertilized in the laboratory and applied to soil before ascocarp formation also produced ascospores with evidence of recombination in progeny, but only known parental alleles were detected. In reciprocal crosses, sclerotia and conidia from both strains functioned as female and male, respectively, indicating A. flavus is hermaphroditic, although the degree of fertility depended upon the parental sources of sclerotia and conidia. All progeny showed maternal inheritance of mitochondria from the sclerotia. Compared to A. flavus populations in crops, soil populations would provide a higher likelihood of exposure of sclerotia to sexually compatible strains and a more diverse source of genetic material for outcrossing.
Topics: Alleles; Aspergillus flavus; Genes, Mitochondrial; Genetic Variation; Reproduction; Soil; Soil Microbiology
PubMed: 26731416
DOI: 10.1371/journal.pone.0146169 -
BMC Genomic Data Mar 2023Biodiversity assessment approaches based on molecular biology techniques such as metabarcoding, RAD-seq, or SnaPshot sequencing are increasingly applied in assessing...
Biodiversity assessment approaches based on molecular biology techniques such as metabarcoding, RAD-seq, or SnaPshot sequencing are increasingly applied in assessing marine and aquatic ecosystems. Here we present a new reference database for fish meta-barcoding based on mitochondrial genes. The Mare-MAGE database contains quality-checked sequences of the mitochondrial 12S ribosomal RNA and Cytochrome c Oxidase I gene. All sequences were obtained from the National Center for Biotechnology Information- GenBank (NBCI-GenBank), the European Nucleotide Archive (ENA), AquaGene Database and BOLD database, and have undergone intensive processing. They were checked for false annotations and non-target anomalies, according to the Integrated Taxonomic Information System (ITIS) and FishBase. The dataset is compiled in ARB-Home, FASTA and Qiime2 formats, and is publicly available from the Mare-MAGE database website ( http://mare-mage.weebly.com/ ). It includes altogether 231,333 COI and 12S rRNA gene sequences of fish, covering 19,506 species of 4,058 genera and 586 families.
Topics: Animals; Databases, Nucleic Acid; DNA Barcoding, Taxonomic; Fishes; Genes, Mitochondrial
PubMed: 36932341
DOI: 10.1186/s12863-023-01119-4 -
FEBS Letters Jan 2017In this paper, we experimentally address the debate about why functional transfer of mitochondrial genes to the nucleus has been halted in some organismal groups and why...
In this paper, we experimentally address the debate about why functional transfer of mitochondrial genes to the nucleus has been halted in some organismal groups and why cytosolic expression of mitochondrial proteins has proven remarkably difficult. By expressing all 13 human mitochondrial-encoded genes with strong mitochondrial-targeting sequences in the cytosol of human cells, we show that all proteins, except ATP8, are transported to the endoplasmic reticulum (ER). These results confirm and extend previous findings based on three mitochondrial genes lacking mitochondrial-targeting sequences that also were relocated to the ER during cytosolic expression. We conclude that subcellular protein targeting constitutes a major barrier to functional transfer of mitochondrial genes to the nuclear genome.
Topics: Endoplasmic Reticulum; Genes, Mitochondrial; Genetic Engineering; Genome, Mitochondrial; HeLa Cells; Humans; Mitochondria; Mitochondrial Proteins; Models, Biological; Recombinant Proteins; Transfection
PubMed: 27928819
DOI: 10.1002/1873-3468.12510