Germline selection shapes human mitochondrial DNA diversity

Approximately 2.4% of the human mitochondrial DNA (mtDNA) genome exhibits common homoplasmic genetic variation. We analyzed 12,975 whole-genome sequences to show that 45.1% of individuals from 1526 mother–offspring pairs harbor a mixed population of mtDNA (heteroplasmy), but the propensity for maternal transmission differs across the mitochondrial genome. Over one generation, we observed selection both for and against variants in specific genomic regions; known variants were more likely to be transmitted than previously unknown variants. However, new heteroplasmies were more likely to match the nuclear genetic ancestry as opposed to the ancestry of the mitochondrial genome on which the mutations occurred, validating our findings in 40,325 individuals. Thus, human mtDNA at the population level is shaped by selective forces within the female germ line under nuclear genetic control, which ensures consistency between the two independent genetic lineages.

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Mitochondrial functionality in female reproduction

Postępy Higieny i Medycyny Doświadczalnej ◽

10.5604/01.3001.0010.3848 ◽

2017 ◽

Vol 71 (1) ◽

pp. 0-0

Author(s):

Łukasz Gąsior ◽

Regina Daszkiewicz ◽

Mateusz Ogórek ◽

Zbigniew Polański

Keyword(s):

Mitochondrial Genome ◽

Germ Cells ◽

Germ Line ◽

Whole Body ◽

Female Reproduction ◽

Normal Number ◽

Female Germ Line ◽

And Function ◽

Role And Function

In most animal species female germ cells are the source of mitochondrial genome for the whole body of individuals. As a source of mitochondrial DNA for future generations the mitochondria in the female germ line undergo dynamic quantitative and qualitative changes. In addition to maintaining the intact template of mitochondrial genome from one generation to another, mitochondrial role in oocytes is much more complex and pleiotropic. The quality of mitochondria determines the ability of meiotic divisions, fertilization ability, and activation after fertilization or sustaining development of a new embryo. The presence of normal number of functional mitochondria is also crucial for proper implantation and pregnancy maintaining. This article addresses issues of mitochondrial role and function in mammalian oocyte and presents new approaches in studies of mitochondrial function in female germ cells.

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Mitochondrial DNA Replacement in Primate Female Germ Line.

Biology of Reproduction ◽

10.1093/biolreprod/85.s1.239 ◽

2011 ◽

Vol 85 (Suppl_1) ◽

pp. 239-239 ◽

Cited By ~ 1

Author(s):

Hyo-Sang Lee ◽

Hong Ma ◽

Maidina Tuohetahuntila ◽

Masahito Tachibana ◽

Michelle Sparman ◽

...

Keyword(s):

Mitochondrial Dna ◽

Germ Line ◽

Female Germ Line

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MitoIMP: A Computational Framework for Imputation of Missing Data in Low-Coverage Human Mitochondrial Genome

Bioinformatics and Biology Insights ◽

10.1177/1177932219873884 ◽

2019 ◽

Vol 13 ◽

pp. 117793221987388

Author(s):

Koji Ishiya ◽

Fuzuki Mizuno ◽

Li Wang ◽

Shintaroh Ueda

Keyword(s):

Mitochondrial Dna ◽

Mitochondrial Genome ◽

Scaling Analysis ◽

Genome Sequences ◽

Computational Framework ◽

Human Mitochondrial Dna ◽

Multiple Resources ◽

Low Coverage ◽

Imputation Procedure ◽

Human Mitochondrial Genome

The incompleteness of partial human mitochondrial genome sequences makes it difficult to perform relevant comparisons among multiple resources. To deal with this issue, we propose a computational framework for deducing missing nucleotides in the human mitochondrial genome. We applied it to worldwide mitochondrial haplogroup lineages and assessed its performance. Our approach can deduce the missing nucleotides with a precision of 0.99 or higher in most human mitochondrial DNA lineages. Furthermore, although low-coverage mitochondrial genome sequences often lead to a blurred relationship in the multidimensional scaling analysis, our approach can correct this positional arrangement according to the corresponding mitochondrial DNA lineages. Therefore, our framework will provide a practical solution to compensate for the lack of genome coverage in partial and fragmented human mitochondrial genome sequences. In this study, we developed an open-source computer program, MitoIMP, implementing our imputation procedure. MitoIMP is freely available from https://github.com/omics-tools/mitoimp .

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Energy, ageing, fidelity and sex: oocyte mitochondrial DNA as a protected genetic template

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2012.0263 ◽

2013 ◽

Vol 368 (1622) ◽

pp. 20120263 ◽

Cited By ~ 31

Author(s):

Wilson B. M. de Paula ◽

Cathy H. Lucas ◽

Ahmed-Noor A. Agip ◽

Gema Vizcay-Barrena ◽

John F. Allen

Keyword(s):

Mitochondrial Dna ◽

Free Radicals ◽

Electron Transport ◽

Oxidative Phosphorylation ◽

Germ Line ◽

Atp Synthesis ◽

Mitochondrial Morphology ◽

Male Gametes ◽

Female Germ Line ◽

Respiratory Electron Transport

Oxidative phosphorylation couples ATP synthesis to respiratory electron transport. In eukaryotes, this coupling occurs in mitochondria, which carry DNA. Respiratory electron transport in the presence of molecular oxygen generates free radicals, reactive oxygen species (ROS), which are mutagenic. In animals, mutational damage to mitochondrial DNA therefore accumulates within the lifespan of the individual. Fertilization generally requires motility of one gamete, and motility requires ATP. It has been proposed that oxidative phosphorylation is nevertheless absent in the special case of quiescent, template mitochondria, that these remain sequestered in oocytes and female germ lines and that oocyte mitochondrial DNA is thus protected from damage, but evidence to support that view has hitherto been lacking. Here we show that female gametes of Aurelia aurita , the common jellyfish, do not transcribe mitochondrial DNA, lack electron transport, and produce no free radicals. In contrast, male gametes actively transcribe mitochondrial genes for respiratory chain components and produce ROS. Electron microscopy shows that this functional division of labour between sperm and egg is accompanied by contrasting mitochondrial morphology. We suggest that mitochondrial anisogamy underlies division of any animal species into two sexes with complementary roles in sexual reproduction. We predict that quiescent oocyte mitochondria contain DNA as an unexpressed template that avoids mutational accumulation by being transmitted through the female germ line. The active descendants of oocyte mitochondria perform oxidative phosphorylation in somatic cells and in male gametes of each new generation, and the mutations that they accumulated are not inherited. We propose that the avoidance of ROS-dependent mutation is the evolutionary pressure underlying maternal mitochondrial inheritance and the developmental origin of the female germ line.

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MUTAGENESIS IN OOCYTES OF DROSOPHILA MELANOGASTER. I. SCHEDULED SYNTHESIS OF NUCLEAR AND MITOCHONDRIAL DNA AND UNSCHEDULED DNA SYNTHESIS

Genetics ◽

10.1093/genetics/104.2.279 ◽

1983 ◽

Vol 104 (2) ◽

pp. 279-299

Author(s):

Mark R Kelley ◽

William R Lee

Keyword(s):

Dna Repair ◽

Mitochondrial Dna ◽

Drosophila Melanogaster ◽

Dna Synthesis ◽

Nuclear Dna ◽

Germ Line ◽

Mutation Induction ◽

Time Interval ◽

Unscheduled Dna Synthesis ◽

Female Germ Line

ABSTRACT As a model system for studying mutagenesis, the oocyte of Drosophila melanogaster has exhibited considerable complexity. Very few experiments have been conducted on the effect of exposing oocytes to chemical mutagens, presumably due to their lower mutational response relative to sperm and spermatids. This lower response may be due either to a change in probability of mutation induction per adduct due to a change in the type of DNA repair or to a lower dose of the mutagen to the female germ line. To study molecular dosimetry and DNA repair in the oocyte, the large number of intracellular constituents (mtDNA, RNA, nucleic acid precursors and large quantities of proteins and lipids) must be separated from nuclear DNA. In this paper we present results showing reliable separation of such molecules enabling us to detect scheduled nuclear and mitochondrial DNA synthesis. We also, by understanding the precise timing of such events, can detect unscheduled DNA synthesis (UDS) as a measure of DNA repair. Furthermore, by comparing the UDS results in a repair competent (Ore-R) vs. a repair deficient (mei-9L1) strain, we have shown the oocyte capable of DNA repair after treatment with ethyl methanesulfonate (EMS). We conclude that the important determinant of mutation induction in oocytes after treatment with EMS is the time interval between DNA alkylation and DNA synthesis after fertilization, i.e., the interruption of continuous DNA repair.

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