Germline selection shapes human mitochondrial DNA diversity

Wei Wei, Salih Tuna, Michael J. Keogh, Katherine R. Smith, Timothy J. Aitman, Phil L. Beales, David L. Bennett, Daniel P. Gale, Maria A.K. Bitner-Glindzicz, Graeme C. Black, Paul Brennan, Perry Elliott, Frances A. Flinter, R. Andres Floto, Henry Houlden, Melita Irving, Ania Koziell, Eamonn R. Maher, Hugh S. Markus, Nicholas W. MorrellWilliam G. Newman, Irene Roberts, John A. Sayer, Kenneth G.C. Smith, Jenny C. Taylor, Hugh Watkins, Andrew R. Webster, Andrew O.M. Wilkie, Catherine Williamson, Sofie Ashford, Christopher J. Penkett, Kathleen E. Stirrups, Augusto Rendon, Willem H. Ouwehand, John R. Bradley, F. Lucy Raymond, Mark Caulfield, Ernest Turro, Patrick F. Chinnery

Research output: Contribution to journalArticlepeer-review

129 Citations (Scopus)


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.

Original languageEnglish
Article numbereaau6520
JournalScience (New York, N.Y.)
Issue number6442
Early online date24 May 2019
Publication statusPublished - 24 May 2019


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