Germline selection shapes human mitochondrial DNA diversity
Authors: Wei Wei , Tuna Salih , Keogh Michael J. , Smith Katherine R. , Aitman Timothy J. , Beales Phil L. , Bennett David L. , Gale Daniel P. , Bitner-Glindzicz Maria A. K. , Black Graeme C. , Brennan Paul , Elliott Perry , Flinter Frances A. , Floto R. Andres , Houlden Henry , Irving Melita , Koziell Ania , Maher Eamonn R. , Markus Hugh S. , Morrell Nicholas W. , Newman William G. , Roberts Irene , Sayer John A. , Smith Kenneth G. C. , Taylor Jenny C. , Watkins Hugh , Webster Andrew R. , Wilkie Andrew O. M. , Williamson Catherine ,   NIHR BioResource–Rare Diseases,   100,000 Genomes Project–Rare Diseases Pilot, Ashford Sofie , Penkett Christopher J. , Stirrups Kathleen E. , Rendon Augusto , Ouwehand Willem H. , Bradley John R. , Raymond F. Lucy , Caulfield Mark , Turro Ernest , Chinnery Patrick F. , Huissoon Aarnoud P. , Crisp-Hihn Abigail , Shaw Adam C. , Mead Adam J. , Levine Adam P. , Thrasher Adrian J. , Bierzynska Agnieszka , Hassan Ahamad , Kumar Ajith , Sanchis-Juan Alba , Richter Alex , Lawrie Allan , Frary Amy J. , Nemeth Andrea H. , Olschewski Andrea , Themistocleous Andreas C. , Browning Andrew C. , Mumford Andrew D. , Schaefer Andrew M. , Marshall Andrew , Wilkie Andrew O. M. , Peacock Andrew , Harper Andrew R. , Webster Andrew R. , Rice Andrew S. C. , Pyle Angela , Koziell Ania , Drazyk Anna M. , Kelly Anne M. , Wagner Annette , Attwood Anthony , De Soyza Anthony , Vandersteen Anthony M. , Moore Anthony T. , Vonk Noordegraaf Anton , Rao Anupama , Herwadkar Archana , Houweling Arjan , Sen Arjune , Rendon Augusto , Worth Austen , Girerd Barbara , Madan Bella , Wilson Brian T. , Diz Carmen Bugarin , Treacy Carmen , Brewer Carole , Campbell Carolyn , Millar Carolyn , Roughley Catherine , Titterton Catherine , Williamson Catherine , Compton Cecilia J. , Danesino Cesare , Thys Chantal , Hadinnapola Charaka , Deshpande Charu , Toh Cheng-Hock , Van Geet Chris , Babbs Christian , Woods Christopher Geoffrey , Penkett Christopher J. , Watt Christopher , Harris Claire , Lentaigne Claire , Palles Claire , Searle Claire , Pilkington Clarissa , Church Colin , French Courtney E. , Samarghitean Crina , Layton D. Mark , Evans Dafydd Gareth , Smedley Damian , Greene Daniel , Hart Daniel , Gale Daniel P. , Kiely David G. , Gosal David , Allsup David J. , Bennett David L. , Montani David , Parry David , Thomas David , Ruddy Deborah M. , Whitehorn Deborah , Grozeva Detelina , Bockenhauer Detlef , Kumararatne Dinakantha , Josifova Dragana , Maher Eamonn R. , Wong Edwin K. S. , Dewhurst Eleanor F. , Louka Eleni , Colby Elizabeth , Ormondroyd Elizabeth , Thomas Ellen , Swietlik Emilia , Staples Emily , Matthews Emma , Woodward Emma , Turro Ernest , Haque Eshika , Raymond F. Lucy , Hu Fengyuan , Lalloo Fiona , Soubrier Florent , Cheng Floria , Flinter Frances A. , Kovacs Gabor , Arno Gavin , Hudson Gavin , Sayer Genevieve , Carr-White Gerald , Coghlan Gerry , Evans Gillian , Black Graeme C. , Hayman Grant , Cook H. Terence , Alachkar Hana , Allen Hana Lango , Kazkaz Hanadi , Stark Hannah , Marschall Hanns-Ulrich , Bogaard Harm , Maxwell Heather , Baxendale Helen E. , Hanson Helen L. , Gall Henning , Houlden Henry , Longhurst Hilary , Fassihi Hiva , Olschewski Horst , Ghofrani Hossein-Ardeschir , Markus Hugh S. , Watkins Hugh , Tomlinson Ian P. , Simeoni Ilenia , Roberts Irene , Edgar J. David M. , Gibbs J. Simon R. , Thaventhiran James E. , Fox James , Ware James S. , Whitworth James , Collins Janine , Suntharalingam Jay , Jolley Jennifer , Martin Jennifer , O’Sullivan Jennifer , Taylor Jenny C. , Chambers Jenny , Maimaris Jesmeen , Clayton-Smith Jill , Pepke-Zaba Joanna , Graham Jodie , Sayer John A. , Westwood John-Paul , Burn John , Davis John , Wharton John , Taylor John , Hoffman Jonathan , Stephens Jonathan , Adlard Julian , von Ziegenweidt Julie , Wessels Julie , Ong Kai Ren , Edwards Karen , Downes Kate , Gibson Kate , Talks Kate , Thomson Kate , Peerlinck Kathelijne , Smith Katherine R. , Yates Katherine , Stirrups Kathleen E. , Freson Kathleen , Snape Katie , Gomez Keith , Sibson Keith , Muir Keith W. , Poole Ken E. S. , Smith Kenneth G. C. , Carss Keren , Marchbank Kevin J. , Gilmour Kimberly C. , Harkness Kirsty , Abulhoul Lara , Scelsi Laura , Robert Leema , Lorenzo Lorena E , Izatt Louise , Side Lucy , Wedderburn Lucy , Howard Luke S. , Greenhalgh Lynn , Chitre Manali , Kurian Manju A. , Humbert Marc , Tischkowitz Marc , Bitner-Glindzicz Maria A. K. , Estiu Maria C. , Erwood Marie , Scully Marie , Caulfield Mark , Gurnell Mark , McCarthy Mark I. , Toshner Mark , Bleda Marta , Vazquez-Lopez Marta , Wilkins Martin R. , Mathias Mary , Brown Matthew , Sims Matthew C. , Hall Matthew , Daniels Matthew J. , Buckland Matthew S. , Traylor Matthew , Haimel Matthias , Cleary Maureen , Dattani Mehul , Eyries Mélanie , Chan Melanie M. Y. , Ekani Melanie N. , Irving Melita , Laffan Michael A. , Gattens Michael , Browning Michael J. , Newnham Michael , Simpson Michael , Wright Michael , Michaelides Michel , Lambert Michele , Saleem Moin , Thomas Moira J. , Mozere Monika , Ahmed Munaza , Brod Naomi Clements , Kingston Nathalie , Shah Neil , Jurkute Neringa , Cooper Nichola , Morrell Nicholas W. , Curry Nicola S. , Burrows Nigel , Koelling Nils , Roy Noemi B. , Shamardina Olga , Spasic-Boskovic Olivera , Sadeghi-Alavijeh Omid , Gresele Paolo , Chinnery Patrick F. , Yong Patrick F. K. , Yu-Wai-Man Patrick , Lyons Paul A. , Aurora Paul , Brennan Paul , Corris Paul , McAlinden Paul , Rayner-Matthews Paula J. , Gordins Pavels , Elliott Perry , Dixon Peter H. , Kelleher Peter , Collins Peter W. , Syrris Petros , Beales Phil L. , Ancliff Philip , Griffiths Philip , Twiss Philip , Yu Ping , Waisfisz Quinten , Floto R. Andres , Tait R. Campbell , Buchan Rachel J. , Linger Rachel , Kazmi Rashid , Sargur Ravishankar B. , Favier Remi , Tan Rhea Y. Y. , Antrobus Richard , Quinton Richard , Scott Richard , Trembath Richard , Horvath Rita , Sarkany Robert N. , Ross-Russell Robert , MacKenzie Ross Robert V. , Condliffe Robin , James Roger , Hague Rosie , Mapeta Rutendo , Armstrong Ruth , Casey Ruth , Noorani Sadia , Tuna Salih , Johnson Sally A. , Malka Samantha , Obaji Samya , Boyce Sara , Goddard Sarah , Rose Sarah J. , Westbury Sarah K. , Mangles Sarah , Mehta Sarju , Hackett Scott , Moledina Shahin , Rahman Shamima , Mohammed Shehla N. , Banka Siddharth , Holden Simon , Pearce Simon , Satchell Simon , Staines Simon , Savic Sinisa , Patel Smita , Douzgou Sofia , Grigoriadou Sofia , Papadia Sofia , Ashford Sofie , Schulman Sol , Park Soo-Mi , Deevi Sri V. V. , Gräf Stefan , Abbs Stephen , Wort Stephen J. , Jolles Stephen , Marks Stephen , Okoli Steven , Cook Stuart , Meacham Stuart , Walker Suellen M. , Shapiro Susan E. , Sivapalaratnam Suthesh , Kuijpers Taco W. , Bariana Tadbir , Bakchoul Tamam , Everington Tamara , Renton Tara , Bueser Teofila , Dent Timothy , Aitman Timothy J. , Biss Tina , Dutt Tina , Fowler Tom , Vale Tom , Lester Tracy , Cole Trevor R. P. , Ganesan Vijeya , Sewell W. A. Carrock , Wei Wei , Erber Wendy N. , Seeger Werner , Kelsall Wilf , Ouwehand Willem H. , Egner William , Newman William G. , Hague William M. , Wood Yvette 
Published: May 2019

Heteroplasmy incidence in mitochondrial DNA

In humans, mitochondrial DNA (mtDNA) is predominantly maternally inherited. mtDNA is under selection to prevent heteroplasmy—the transmission of multiple genetic variants into the next generation. Wei
et al.
explored human mtDNA sequences to determine mtDNA genome structure, selection, and transmission. Whole-genome sequencing revealed that about 45% of individuals carry heteroplasmic mtDNA sequences at levels greater than 1% of their total mtDNA. Furthermore, studies of more than 1500 mother-offspring pairs indicated that the female line selected which mtDNA variants were passed on to children. This effect was influenced by the mother's nuclear genetic background. Thus, mtDNA is under selection at specific loci in the human germ line.

Science
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