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Biparental inheritance of mitochondrial DNA revisited

Nature Reviews Genetics volume 22, pages 477–478 (2021)Cite this article

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Evidence for a biparental mode of mitochondrial DNA (mtDNA) inheritance has been sparse and remains controversial. Recent studies using a range of complementary techniques do not support paternal transmission of mtDNA and highlight the co-amplification of rare, concatenated nuclear mtDNA segments as a technical artefact that may explain previous observations.

First demonstrated in humans in 1980 (ref.1), strict maternal inheritance of mitochondrial DNA (mtDNA) has stood the test of time, with the only counterexample2, a single case report suggesting paternal mtDNA inheritance, never having been convincingly replicated. Uniparental inheritance enables rapid cytoplasmic genome evolution, contributing to extensive polymorphism in the extant population. This has been exploited by population geneticists to map human migration throughout history, and to match biological samples in forensic science. Most human cells contain >100 copies of mtDNA, and a mixed mtDNA population in the same individual is termed ‘heteroplasmy’. Precise heteroplasmy levels change rapidly upon transmission to offspring owing to a genetic bottleneck during oogenesis. Thus, novel variants are either lost or progress to fixation within a few generations, explaining why high heteroplasmy levels are uncommon in the population. In 2018, a controversial study describing high levels of heteroplasmy in three multigenerational families proposed a previously unrecognized biparental form of mtDNA inheritance3. However, newly published data obtained using a range of complementary techniques do not support paternal transmission and suggest a more parsimonious explanation (Supplementary Table 1).

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References

  1. Giles, R. E., Blanc, H., Cann, H. M. & Wallace, D. C. Maternal inheritance of human mitochondrial DNA. Proc. Natl Acad. Sci. USA 77, 6715–6719 (1980).

    Article  CAS  Google Scholar 

  2. Schwartz, M. & Vissing, J. Paternal inheritance of mitochondrial DNA. N. Engl. J. Med. 347, 576–580 (2002).

    Article  Google Scholar 

  3. Luo, S. et al. Biparental inheritance of mitochondrial DNA in humans. Proc. Natl Acad. Sci. USA 115, 13039–13044 (2018).

    Article  CAS  Google Scholar 

  4. McWilliams, T. G. & Suomalainen, A. Mitochondrial DNA can be inherited from fathers, not just mothers. Nature 565, 296–297 (2019).

    Article  CAS  Google Scholar 

  5. Salas, A., Schönherr, S., Bandelt, H.-J., Gómez-Carballa, A. & Weissensteiner, H. Extraordinary claims require extraordinary evidence in asserted mtDNA biparental inheritance. Forensic Sci. Int. Genet. 47, 102274 (2020).

    Article  CAS  Google Scholar 

  6. Balciuniene, J. & Balciunas, D. A Nuclear mtDNA concatemer (Mega-NUMT) could mimic paternal inheritance of mitochondrial genome. Front. Genet. 10, 518 (2019).

    Article  CAS  Google Scholar 

  7. Rius, R. et al. Biparental inheritance of mitochondrial DNA in humans is not a common phenomenon. Genet. Med. 21, 2823–2826 (2019).

    Article  CAS  Google Scholar 

  8. Wei, W. et al. Nuclear-mitochondrial DNA segments resemble paternally inherited mitochondrial DNA in humans. Nat. Commun. 11, 1740 (2020).

    Article  CAS  Google Scholar 

  9. Lutz-Bonengel, S. et al. Evidence for multi-copy Mega-NUMTs in the human genome. Nucleic Acids Res. 49, 1517–1531 (2021).

    Article  Google Scholar 

  10. Bai, R. et al. Interference of nuclear mitochondrial DNA segments in mitochondrial DNA testing resembles biparental transmission of mitochondrial DNA in humans. Genet. Med. https://doi.org/10.1038/s41436-021-01166-1 (2021).

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors acknowledge funding from the Wellcome Trust (203141/Z/16/Z and 212219/Z/18/Z), the Medical Research Council Mitochondrial Biology Unit (MC_UU_00015/9) and the NIHR Biomedical Research Centres at Cambridge, Oxford and Great Ormond Street.

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Authors and Affiliations

  1. Wellcome Centre for Human Genetics and the NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK

    Alistair T. Pagnamenta

  2. Department of Clinical Neurosciences and the MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK

    Wei Wei & Patrick F. Chinnery

  3. UCL Great Ormond Street Institute of Child Health, London, UK

    Shamima Rahman

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  1. Alistair T. Pagnamenta
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  2. Wei Wei
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  4. Patrick F. Chinnery
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Correspondence to Patrick F. Chinnery.

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Pagnamenta, A.T., Wei, W., Rahman, S. et al. Biparental inheritance of mitochondrial DNA revisited. Nat Rev Genet 22, 477–478 (2021). https://doi.org/10.1038/s41576-021-00380-6

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