Science, Vol.364, No.6442, 749-+, 2019
Germline selection shapes human mitochondrial DNA diversity
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 ,
Attwood A ,
Brown M ,
Brod NC ,
Crisp-Hihn A ,
Davis J ,
Deevi SVV ,
Dewhurst EF ,
Edwards K ,
Erwood M ,
Fox J ,
Frary AJ ,
Hu FY ,
Jolley J ,
Kingston N ,
Linger R ,
Mapeta R ,
Martin J ,
Meacham S ,
Papadia S ,
Rayner-Matthews PJ ,
Samarghitean C ,
Shamardina O ,
Simeoni I ,
Staines S ,
Staples E ,
Stark H ,
Stephens J ,
Titterton C ,
Tuna S ,
von Ziegenweidt J ,
Watt C ,
Whitehorn D ,
Wood Y ,
Yates K ,
Yu P ,
James R ,
Ashford S ,
Penkett CJ ,
Stirrups KE ,
Bariana T ,
Lentaigne C ,
Sivapalaratnam S ,
Westbury SK ,
Allsup DJ ,
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Curry NS ,
Downes K ,
Dutt T ,
Erber WN ,
Evans G ,
Everington T ,
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Kazmi R ,
Kelly AM ,
Lambert M ,
Madan B ,
Mangles S ,
Mathias M ,
Millar C ,
Obaji S ,
Peerlinck K ,
Roughley C ,
Schulman S ,
Scully M ,
Shapiro SE ,
Sibson K ,
Simeoni I ,
Sims MC ,
Tait RC ,
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Thys C ,
Toh CH ,
Geet C ,
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Papadia S ,
Mumford AD ,
Ouwehand WH ,
Freson K ,
Laffan MA ,
Tan RYY ,
Harkness K ,
Mehta S ,
Muir KW ,
Hassan A ,
Traylor M ,
Drazyk AM ,
Markus HS ,
Parry D ,
Ahmed M ,
Kazkaz H ,
Vandersteen AM ,
Aitman TJ ,
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Thomson K ,
Dent T ,
Brennan P ,
Buchan RJ ,
Bueser T ,
Carr-White G ,
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Daniels MJ ,
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Ware JS ,
Watkins H ,
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Estiu MC ,
Hague WM ,
Marschall HU ,
Vazquez-Lopez M ,
Williamson C ,
Arno G ,
Dewhurst EF ,
Erwood M ,
French CE ,
Michaelides M ,
Moore AT ,
Sanchis-Juan A ,
Carss K ,
Webster AR ,
Raymond FL ,
Chinnery PF ,
Griffiths P ,
Horvath R ,
Hudson G ,
Jurkute N ,
Pyle A ,
Wei W ,
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Whitworth J ,
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Evans DG ,
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Hanson HL ,
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Izatt L ,
Kumar A ,
Lalloo F ,
Ong KR ,
Park SM ,
Searle C ,
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Snape K ,
Woodward E ,
Tischkowitz M ,
Maher ER ,
Carss K ,
Dewhurst EF ,
Erwood M ,
French CE ,
Grozeva D ,
Kurian MA ,
Themistocleous AC ,
Gosal D ,
Horvath R ,
Marshall A ,
Matthews E ,
McCarthy MI ,
Renton T ,
Rice ASC ,
Vale T ,
Walker SM ,
Woods CG ,
Bennett DL ,
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Allen HL ,
Savic S ,
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Browning MJ ,
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Lyons PA ,
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Samarghitean C ,
Sargur RB ,
Sewell WAC ,
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Worth A ,
Yong PFK ,
Kuijpers TW ,
Thrasher AJ ,
Smith KGC ,
Levine AP ,
Sadeghi-Alavijeh O ,
Wong EKS ,
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McAlinden P ,
Marchbank KJ ,
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Gale DP ,
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Coghlan G ,
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Danesino C ,
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Ghofrani HA ,
Gibbs JSR ,
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Howard LS ,
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Kiely DG ,
Kovacs G ,
Lawrie A ,
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Martin J ,
Moledina S ,
Montani D ,
Newnham M ,
Olschewski A ,
Olschewski H ,
Peacock A ,
Pepke-Zaba J ,
Scelsi L ,
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Suntharalingam J ,
Toshner M ,
Treacy C ,
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Noordegraaf AV ,
Waisfisz Q ,
Wharton J ,
Wilkins MR ,
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Louka E ,
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Okoli S ,
Roberts I ,
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Diz CB ,
Colby E ,
Ekani MN ,
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Koziell A ,
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Rendon A ,
Scott R ,
Smedley D ,
Smith KR ,
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Caulfield M ,
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Chitre M ,
Dewhurst EF ,
Floto RA ,
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Gurnell M ,
Holden S ,
Kelsall W ,
Mehta S ,
Poole KES ,
Ross-Russell R ,
Spasic-Boskovic O ,
Twiss P ,
Wagner A ,
Banka S ,
Black GC ,
Clayton-Smith J ,
Douzgou S ,
Newman WG ,
Abulhoul L ,
Aurora P ,
Bockenhauer D ,
Cleary M ,
Dattani M ,
Ganesan V ,
Pilkington C ,
Rahman S ,
Shah N ,
Wedderburn L ,
Bitner-Glindzicz MAK ,
Bueser T ,
Compton CJ ,
Deshpande C ,
Fassihi H ,
Haque E ,
Izatt L ,
Josifova D ,
Mohammed SN ,
Robert L ,
Rose SJ ,
Ruddy DM ,
Sarkany RN ,
Sayer G ,
Shaw AC ,
Irving M ,
Flinter FA ,
Campbell C ,
Gibson K ,
Koelling N ,
Lester T ,
Nemeth AH ,
Palles C ,
Patel S ,
Roy NB ,
Sen A ,
Taylor J ,
Tomlinson IP ,
Taylor JC ,
Wilkie AOM ,
Arno G ,
Malka S ,
Michaelides M ,
Moore AT ,
Webster AR ,
Brennan P ,
Browning AC ,
Burn J ,
Chinnery PF ,
De Soyza A ,
Graham J ,
Horvath R ,
Pearce S ,
Quinton R ,
Schaefer AM ,
Wilson BT ,
Wright M ,
Yu-Wai-Man P ,
Sayer JA ,
Simpson M ,
Syrris P ,
Elliott P ,
Houlden H ,
Beales PL ,
Ashford S ,
Penkett CJ ,
Stirrups KE ,
Rendon A ,
Ouwehand WH ,
Bradley JR ,
Raymond FL ,
Caulfield M ,
Turro E ,
Chinnery PF
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.
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