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Germline selection shapes human mitochondrial DNA diversity.

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    Mitochondrial DNA (mtDNA) heteroplasmy is common, with selection influencing variant transmission across generations. Nuclear genetic control ensures consistency between nuclear and mitochondrial DNA lineages.

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    Area of Science:

    • Genetics
    • Human Evolution
    • Population Genetics

    Background:

    • Mitochondrial DNA (mtDNA) constitutes a small fraction of the human genome but harbors genetic variation.
    • Heteroplasmy, the presence of multiple mtDNA populations within an individual, is observed in a significant portion of the human population.

    Purpose of the Study:

    • To investigate the prevalence and transmission patterns of mitochondrial DNA heteroplasmy.
    • To understand the selective forces acting on mtDNA variants during maternal inheritance.
    • To explore the relationship between nuclear and mitochondrial genetic ancestry.

    Main Methods:

    • Analysis of 12,975 whole-genome sequences from 1526 mother-offspring pairs.
    • Examination of mtDNA variant transmission across one generation.
    • Validation of findings in a larger cohort of 40,325 individuals.

    Main Results:

    • 45.1% of individuals exhibit mtDNA heteroplasmy.
    • Differential selection for and against mtDNA variants occurs across the genome.
    • Newly arising heteroplasmies tend to align with nuclear genetic ancestry.

    Conclusions:

    • Human mtDNA populations are shaped by selection within the female germline.
    • Nuclear genetic factors influence the transmission and consistency of mtDNA.
    • This process ensures coordination between independent nuclear and mitochondrial genetic lineages.