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Science. 2019 May 24;364(6442). pii: eaau6520. doi: 10.1126/science.aau6520. Epub 2019 May 23.

Germline selection shapes human mitochondrial DNA diversity.

Collaborators (360)

Huissoon AP, Crisp-Hihn A, Shaw AC, Mead AJ, Levine AP, Thrasher AJ, Bierzynska A, Hassan A, Kumar A, Sanchis-Juan A, Richter A, Lawrie A, Frary AJ, Nemeth AH, Olschewski A, Themistocleous AC, Browning AC, Mumford AD, Schaefer AM, Marshall A, Wilkie AOM, Peacock A, Harper AR, Webster AR, Rice ASC, Pyle A, Koziell A, Drazyk AM, Kelly AM, Wagner A, Attwood A, De Soyza A, Vandersteen AM, Moore AT, Vonk Noordegraaf A, Rao A, Herwadkar A, Houweling A, Sen A, Rendon A, Worth A, Girerd B, Madan B, Wilson BT, Diz CB, Treacy C, Brewer C, Campbell C, Millar C, Roughley C, Titterton C, Williamson C, Compton CJ, Danesino C, Thys C, Hadinnapola C, Deshpande C, Toh CH, Van Geet C, Babbs C, Woods CG, Penkett CJ, Watt C, Harris C, Lentaigne C, Palles C, Searle C, Pilkington C, Church C, French CE, Samarghitean C, Layton DM, Evans DG, Smedley D, Greene D, Hart D, Gale DP, Kiely DG, Gosal D, Allsup DJ, Bennett DL, Montani D, Parry D, Thomas D, Ruddy DM, Whitehorn D, Grozeva D, Bockenhauer D, Kumararatne D, Josifova D, Maher ER, Wong EKS, Dewhurst EF, Louka E, Colby E, Ormondroyd E, Thomas E, Swietlik E, Staples E, Matthews E, Woodward E, Turro E, Haque E, Raymond FL, Hu F, Lalloo F, Soubrier F, Cheng F, Flinter FA, Kovacs G, Arno G, Hudson G, Sayer G, Carr-White G, Coghlan G, Evans G, Black GC, Hayman G, Cook HT, Alachkar H, Allen HL, Kazkaz H, Stark H, Marschall HU, Bogaard H, Maxwell H, Baxendale HE, Hanson HL, Gall H, Houlden H, Longhurst H, Fassihi H, Olschewski H, Ghofrani HA, Markus HS, Watkins H, Tomlinson IP, Simeoni I, Roberts I, Edgar JDM, Gibbs JSR, Thaventhiran JE, Fox J, Ware JS, Whitworth J, Collins J, Suntharalingam J, Jolley J, Martin J, O'Sullivan J, Taylor JC, Chambers J, Maimaris J, Clayton-Smith J, Pepke-Zaba J, Graham J, Sayer JA, Westwood JP, Burn J, Davis J, Wharton J, Taylor J, Hoffman J, Stephens J, Adlard J, von Ziegenweidt J, Wessels J, Ong KR, Edwards K, Downes K, Gibson K, Talks K, Thomson K, Peerlinck K, Smith KR, Yates K, Stirrups KE, Freson K, Snape K, Gomez K, Sibson K, Muir KW, Poole KES, Smith KGC, Carss K, Marchbank KJ, Gilmour KC, Harkness K, Abulhoul L, Scelsi L, Robert L, Lorenzo LE, Izatt L, Side L, Wedderburn L, Howard LS, Greenhalgh L, Chitre M, Kurian MA, Humbert M, Tischkowitz M, Bitner-Glindzicz MAK, Estiu MC, Erwood M, Scully M, Caulfield M, Gurnell M, McCarthy MI, Toshner M, Bleda M, Vazquez-Lopez M, Wilkins MR, Mathias M, Brown M, Sims MC, Hall M, Daniels MJ, Buckland MS, Traylor M, Haimel M, Cleary M, Dattani M, Eyries M, Chan MMY, Ekani MN, Irving M, Laffan MA, Gattens M, Browning MJ, Newnham M, Simpson M, Wright M, Michaelides M, Lambert M, Saleem M, Thomas MJ, Mozere M, Ahmed M, Brod NC, Kingston N, Shah N, Jurkute N, Cooper N, Morrell NW, Curry NS, Burrows N, Koelling N, Roy NB, Shamardina O, Spasic-Boskovic O, Sadeghi-Alavijeh O, Gresele P, Chinnery PF, Yong PFK, Yu-Wai-Man P, Lyons PA, Aurora P, Brennan P, Corris P, McAlinden P, Rayner-Matthews PJ, Gordins P, Elliott P, Dixon PH, Kelleher P, Collins PW, Syrris P, Beales PL, Ancliff P, Griffiths P, Twiss P, Yu P, Waisfisz Q, Floto RA, Tait RC, Buchan RJ, Linger R, Kazmi R, Sargur RB, Favier R, Tan RYY, Antrobus R, Quinton R, Scott R, Trembath R, Horvath R, Sarkany RN, Ross-Russell R, MacKenzie Ross RV, Condliffe R, James R, Hague R, Mapeta R, Armstrong R, Casey R, Noorani S, Tuna S, Johnson SA, Malka S, Obaji S, Boyce S, Goddard S, Rose SJ, Westbury SK, Mangles S, Mehta S, Hackett S, Moledina S, Rahman S, Mohammed SN, Banka S, Holden S, Pearce S, Satchell S, Staines S, Savic S, Patel S, Douzgou S, Grigoriadou S, Papadia S, Ashford S, Schulman S, Park SM, Deevi SVV, Gräf S, Abbs S, Wort SJ, Jolles S, Marks S, Okoli S, Cook S, Meacham S, Walker SM, Shapiro SE, Sivapalaratnam S, Kuijpers TW, Bariana T, Bakchoul T, Everington T, Renton T, Bueser T, Dent T, Aitman TJ, Biss T, Dutt T, Fowler T, Vale T, Lester T, Cole TRP, Ganesan V, Sewell WAC, Wei W, Erber WN, Seeger W, Kelsall W, Ouwehand WH, Egner W, Newman WG, Hague WM, Wood Y.

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.

PMID:
31123110
DOI:
10.1126/science.aau6520
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