@article{0592ca3f72534b31a6d62dd7d20e0adc,
title = "Germline selection shapes human mitochondrial DNA diversity",
abstract = "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.",
keywords = "LEIGH-DISEASE, HETEROPLASMY, MTDNA, MUTATIONS, GENOME, TRANSCRIPTION, REPLICATION, ASSOCIATION, REPLACEMENT, SEQUENCE",
author = "{NIHR BioResource-Rare Dis} and {100000 Genomes Project-Rare Dis} and Wei Wei and Salih Tuna and Keogh, {Michael J.} and Smith, {Katherine R.} and Aitman, {Timothy J.} and Beales, {Phil L.} and Bennett, {David L.} and Gale, {Daniel P.} and Bitner-Glindzicz, {Maria A. K.} and Black, {Graeme C.} and Paul Brennan and Perry Elliott and Flinter, {Frances A.} and Floto, {R. Andres} and Henry Houlden and Melita Irving and Ania Koziell and Maher, {Eamonn R.} and Markus, {Hugh S.} and Morrell, {Nicholas W.} and Newman, {William G.} and Irene Roberts and Sayer, {John A.} and Smith, {Kenneth G. C.} and Taylor, {Jenny C.} and Hugh Watkins and Webster, {Andrew R.} and Wilkie, {Andrew O. M.} and Catherine Williamson and Anthony Attwood and Matthew Brown and Brod, {Naomi Clements} and Abigail Crisp-Hihn and John Davis and Deevi, {Sri V. V.} and Dewhurst, {Eleanor F.} and Karen Edwards and Marie Erwood and James Fox and Frary, {Amy J.} and Fengyuan Hu and Jennifer Jolley and Nathalie Kingston and Rachel Linger and Rutendo Mapeta and Jennifer Martin and Stuart Meacham and Sofia Papadia and Aitman, {Timothy J.} and Kate Thomson and Ian Tomlinson",
year = "2019",
month = may,
day = "24",
doi = "10.1126/science.aau6520",
language = "English",
volume = "364",
pages = "749--+",
journal = "Science",
issn = "0036-8075",
publisher = "AMER ASSOC ADVANCEMENT SCIENCE",
number = "6442",
}