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Germline selection shapes human mitochondrial DNA diversity

Lookup NU author(s): Dr Paul Brennan, Professor John SayerORCiD, Professor Kevin MarchbankORCiD, Professor Patrick Chinnery

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Abstract

Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.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.

Publication metadata

Author(s): Wei W, Tuna S, Keogh MJ, Smith KR, Aitman TJ, Beales PL, Bennett DL, Gale DP, Bitner-Glindzicz MAK, Black GC, Brennan P, Elliott P, Flinter FA, Floto RA, Houlden H, Irving M, Koziell A, Maher ER, Markus HS, Morrell NW, Newman WG, Roberts I, Sayer JA, Smith KGC, Taylor JC, Watkins H, Webster AR, Wilkie AOM, Williamson C, NIHR BioResource - Rare Diseases, 100,000 Genomes Project - Rare Diseases Pilot, Ashford S, Penkett CJ, Stirrups KE, Rendon A, Ouwehand WH, Bradley JR, Raymond FL, Caulfield M, Turro E, Chinnery PF

Publication type: Article

Publication status: Published

Journal: Science

Year: 2019

Volume: 364

Issue: 6442

Print publication date: 24/05/2019

Acceptance date: 03/04/2019

ISSN (print): 0036-8075

ISSN (electronic): 1095-9203

Publisher: American Association for the Advancement of Science (AAAS)

URL: https://doi.org/10.1126/science.aau6520

DOI: 10.1126/science.aau6520

PubMed id: 31123110

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