Open AccessGermline selection shapes human mitochondrial DNA diversity
Author(s) -
Wei Wei,
Salih Tuna,
Michael J. Keogh,
Katherine R. Smith,
Timothy J. Aitman,
Phil L. Beales,
David Bennett,
Daniel P. Gale,
Maria BitnerGlindzicz,
Graeme Black,
Paul Brennan,
Perry Elliott,
Frances Flinter,
R. Andres Floto,
Henry Houlden,
Melita Irving,
Ania Koziell,
Eamonn R. Maher,
Hugh S. Markus,
Nicholas W. Morrell,
William 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 Stirrups,
Augusto Rendon,
Willem H. Ouwehand,
John R. Bradley,
F. Lucy Raymond,
Mark J. Caulfield,
Ernest Turro,
Patrick F. Chinnery,
Aarnoud Huissoon,
Abigail Crisp-Hihn,
Adam Shaw,
Adam J. Mead,
Adam P. Levine,
Adrian J. Thrasher,
Agnieszka Bierżyńska,
Ahamad Hassan,
Ajith Kumar,
Alba SanchisJuan,
Alex Richter,
Allan Lawrie,
Amy Frary,
Andrea H. Németh,
Andrea Olschewski,
Andreas C. Themistocleous,
Andrew C. Browning,
Andrew Mumford,
Andrew M. Schaefer,
Andrew Marshall,
Andrew Peacock,
Andrew R. Harper,
Andrew S.C. Rice,
Angela Pyle,
Anna M. Drazyk,
Anne M. Kelly,
Annette Wagner,
Anthony Attwood,
Anthony De Soyza,
Anthony M. Vandersteen,
Anthony T. Moore,
Anton Vonk Noordegraaf,
Anupama Rao,
Archana Herwadkar,
Arjan C. Houweling,
Arjune Sen,
Austen Worth,
Barbara Girerd,
Bella Madan,
Brian T. Wilson,
Carmen Bugarin Diz,
Carmen Treacy,
Carole Brewer,
Carolyn Campbell,
Carolyn M. Millar,
Catherine Roughley,
Catherine Titterton,
Cecilia Compton,
Cesare Danesino,
Chantal Thys,
Charaka Hadinnapola,
Charu Deshpande,
ChengHock Toh,
Chris Van Geet,
Christian Babbs,
C. Geoffrey Woods,
Christopher D. Watt,
Claire Harris,
Claire Lentaigne,
Claire Palles,
Claire Searle,
Clarissa Pilkington,
Colin Church,
Courtney E. French,
Crina Samarghitean,
D. Mark Layton,
D. Gareth Evans,
Damian Smedley,
Daniel Greene,
Daniel J. Hart,
David G. Kiely,
David Gosal,
David Allsup,
David Montani,
David Parry,
David Thomas,
Deborah Ruddy,
Deborah Whitehorn,
Detelina Grozeva,
Detlef Böckenhauer,
Dinakantha Kumararatne,
Dragana Josifova,
Edwin K.S. Wong,
Eleanor Dewhurst,
Eleni Louka,
Elizabeth Colby,
Elizabeth Ormondroyd,
Ellen Thomas,
Emilia M. Swietlik,
Emily Staples,
Emma Matthews,
Emma R. Woodward,
Eshika Haque,
Fengyuan Hu,
Fiona Lalloo,
Florent Soubrier,
Floria Cheng,
Gábor Kovács,
Gavin Arno,
Gavin Hudson,
Genevieve Sayer,
Gerald CarrWhite,
Gerry Coghlan,
Gillian Evans,
Grant Hayman,
H. Terence Cook,
Hana Alachkar,
Hana Lango Allen,
Hanadi Kazkaz,
Hannah Stark,
HannsUlrich Marschall,
Harm Jan Bogaard,
Heather Maxwell,
Helen Baxendale,
Helen Hanson,
Henning Gall,
Hilary Longhurst,
Hiva Fassihi,
Horst Olschewski,
Hossein A. Ghofrani,
Ian Tomlinson,
Ilenia Simeoni,
David Edgar,
J. Simon R. Gibbs,
James E. Thaventhiran,
James Fox,
James S. Ware,
James W. Whitworth,
Janine Collins,
Jay Suntharalingam,
Jennifer Jolley,
Jennifer M. Martin,
Jennifer O’Sullivan,
Jenny Chambers,
Jesmeen Maimaris,
Jill ClaytonSmith,
Joanna PepkeŻaba,
Jodie Graham,
JohnPaul Westwood,
John Burn,
John Davis,
John Wharton,
John Taylor,
Jonathan Hoffman,
Jonathan Stephens,
Julian Adlard,
Julie von Ziegenweidt,
Julie Wessels,
Kai Ren Ong,
Karen L. Edwards,
Kate Downes,
Kate Gibson,
Kate Talks,
Kate Thomson,
Kathelijne Peerlinck,
Katherine P. Yates,
Kathleen Freson,
Katie Snape,
Keith Gomez,
Keith Sibson,
Keith W. Muir,
Ken Poole,
Keren Carss,
Kevin J. Marchbank,
Kimberly Gilmour,
Kirsty Harkness,
Lara Abulhoul,
Laura Scelsi,
Leema Robert,
Lorena Lorenzo,
Louise Izatt,
Lucy Side,
Lucy R. Wedderburn,
Luke Howard,
Lynn Greenhalgh,
Manali Chitre,
Manju A. Kurian,
Marc Humbert,
Marc Tischkowitz,
Maria C. Estiú,
Marie Erwood,
Marie Scully,
Mark Gurnell,
Mark I. McCarthy,
Mark Toshner,
Marta Bleda,
Marta VazquezLopez,
Martin R. Wilkins,
Mary Mathias,
Matthew A. Brown,
Matthew C. Sims,
Matthew Hall,
Matthew J. Daniels,
Matthew Buckland,
Matthew Traylor,
Matthias Haimel,
Maureen Cleary,
Mehul Dattani,
Mélanie Eyries,
Melanie Chan,
Melanie N. Ekani,
Michael Laffan,
Michael Gattens,
Michael J. Browning,
Michael Newnham,
Michael A. Simpson,
Michael Wright,
Michel Michaelides,
Michele P. Lambert,
Moin A. Saleem,
Moira Thomas,
Monika Mozere,
Munaza Ahmed,
Naomi Clements Brod,
Nathalie Kingston,
Neil V. Shah,
Neringa Jurkutė,
Nichola Cooper,
Nicola Curry,
Nigel Burrows,
Nils Koelling,
Noémi Roy,
Olga Shamardina,
Olivera Spasić-Bošković,
Omid SadeghiAlavijeh,
Paolo Gresele,
Patrick Yong,
Patrick YuWaiMan,
Paul Lyons,
Paul Aurora,
Paul A. Corris,
Paul McAlinden,
Paula Rayner-Matthews,
Pavels Gordins,
Peter H. Dixon,
Peter Kelleher,
Peter W. Collins,
Petros Syrris,
Philip Ancliff,
Philip G. Griffiths,
Philip Twiss,
Ping Yu,
Quinten Waisfisz,
R. Campbell Tait,
Rachel Buchan,
Rachel Linger,
Rashid Kazmi,
Ravishankar Sargur,
Rémi Favier,
Rhea Tan,
Richard Antrobus,
Richard Quinton,
Richard H. Scott,
Richard C. Trembath,
Rita Horváth,
Robert N. Sarkany,
Robert RossRussell,
Robert V. MacKenzie Ross,
Robin Condliffe,
Roger James,
Rosie Hague,
Rutendo Mapeta,
Ruth Armstrong,
Ruth Casey,
Sadia Noorani,
Sally Johnson,
Samantha Malka,
Samya Obaji,
Sara Boyce,
Sarah Goddard,
Sarah J. Rose,
Sarah K. Westbury,
Sarah Mangles,
Sarju Mehta,
Scott Hackett,
Shahin Moledina,
Shamima Rahman,
Shehla Mohammed,
Siddharth Banka,
Simon Holden,
Simon H. S. Pearce,
Simon C. Satchell,
Simon Staines,
Sinisa Savic,
Smita Y. Patel,
Sofia Douzgou,
Sofia Grigoriadou,
Sofia Papadia,
Sol Schulman,
SooMi Park,
Sri V. V. Deevi,
Stefan Ting Graf,
Stephen Abbs,
Stephen J. Wort,
Stephen Jolles,
Stephen D. Marks,
Steven Okoli,
Stuart A. Cook,
Stuart Meacham,
Suellen M. Walker,
Susan Shapiro,
Suthesh Sivapalaratnam,
Taco W. Kuijpers,
Tadbir K. Bariana,
Tamam Bakchoul,
Tamara Everington,
Tara Renton,
Teofila Bueser,
Timothy Dent,
Tina Biss,
Tina Dutt,
Tom Fowler,
Tom Vale,
Tracy Lester,
Trevor Cole,
Vijeya Ganesan,
William A. Sewell,
Wendy N. Erber,
Werner Seeger,
Wilf Kelsall,
William Egner,
William M. Hague,
Yvette Wood
Publication year - 2019
Publication title -
science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 12.556
H-Index - 1186
eISSN - 1095-9203
pISSN - 0036-8075
DOI - 10.1126/science.aau6520
Subject(s) - heteroplasmy , mitochondrial dna , biology , genetics , germline , human mitochondrial genetics , genome , selection (genetic algorithm) , genetic diversity , mtdna control region , evolutionary biology , haplotype , allele , gene , population , demography , artificial intelligence , sociology , computer science
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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