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Large-scale genetic analysis reveals mammalian mtDNA heteroplasmy dynamics and variance increase through lifetimes and generations

Author

Listed:
  • Joerg P. Burgstaller

    (Biotechnology in Animal Production
    University of Veterinary Medicine Vienna
    Imperial College London)

  • Thomas Kolbe

    (Biomodels Austria, University of Veterinary Medicine Vienna
    University of Natural Resources and Life Sciences)

  • Vitezslav Havlicek

    (University of Veterinary Medicine)

  • Stephanie Hembach

    (Biotechnology in Animal Production)

  • Joanna Poulton

    (University of Oxford)

  • Jaroslav Piálek

    (Institute of Vertebrate Biology of the Czech Academy of Sciences)

  • Ralf Steinborn

    (University of Veterinary Medicine Vienna)

  • Thomas Rülicke

    (University of Veterinary Medicine Vienna)

  • Gottfried Brem

    (Biotechnology in Animal Production
    University of Veterinary Medicine Vienna)

  • Nick S. Jones

    (Imperial College London
    Imperial College London)

  • Iain G. Johnston

    (University of Birmingham)

Abstract

Vital mitochondrial DNA (mtDNA) populations exist in cells and may consist of heteroplasmic mixtures of mtDNA types. The evolution of these heteroplasmic populations through development, ageing, and generations is central to genetic diseases, but is poorly understood in mammals. Here we dissect these population dynamics using a dataset of unprecedented size and temporal span, comprising 1947 single-cell oocyte and 899 somatic measurements of heteroplasmy change throughout lifetimes and generations in two genetically distinct mouse models. We provide a novel and detailed quantitative characterisation of the linear increase in heteroplasmy variance throughout mammalian life courses in oocytes and pups. We find that differences in mean heteroplasmy are induced between generations, and the heteroplasmy of germline and somatic precursors diverge early in development, with a haplotype-specific direction of segregation. We develop stochastic theory predicting the implications of these dynamics for ageing and disease manifestation and discuss its application to human mtDNA dynamics.

Suggested Citation

  • Joerg P. Burgstaller & Thomas Kolbe & Vitezslav Havlicek & Stephanie Hembach & Joanna Poulton & Jaroslav Piálek & Ralf Steinborn & Thomas Rülicke & Gottfried Brem & Nick S. Jones & Iain G. Johnston, 2018. "Large-scale genetic analysis reveals mammalian mtDNA heteroplasmy dynamics and variance increase through lifetimes and generations," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04797-2
    DOI: 10.1038/s41467-018-04797-2
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    Cited by:

    1. Joke Mertens & Florence Belva & Aafke P. A. van Montfoort & Marius Regin & Filippo Zambelli & Sara Seneca & Edouard Couvreu de Deckersberg & Maryse Bonduelle & Herman Tournaye & Katrien Stouffs & Kurt, 2024. "Children born after assisted reproduction more commonly carry a mitochondrial genotype associating with low birthweight," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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