← Back to cohort
Germline selection shapes human mitochondrial DNA diversity
Wei Wei, Salih Tuna, Michael J. Keogh, Katherine R. Smith, Timothy J. Aitman, Phil L. Beales, David Bennett, Daniel P. Gale, Graeme C. Black, Paul Brennan, Perry Elliott, Frances Flinter, R. Andrés Floto, Henry Houlden, Melita Irving, Eamonn R. Maher, Hugh S. Markus, Nicholas W. Morrell, William G. Newman, Irene Roberts, John A. Sayer, Jenny C. Taylor, Hugh Watkins, Andrew O.M. Wilkie, Sofie Ashford, Christopher J. Penkett, Kathleen Stirrups, Augusto Rendon, Willem H. Ouwehand, John R. Bradley, F. Lucy Raymond, 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 Sanchis‐Juan, 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, Cheng‐Hock 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 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 Carr‐White, Gerry Coghlan, Gillian Evans, Grant Hayman, H. Terence Cook, Hana Alachkar, Hana Lango Allen, Hanadi Kazkaz, Hannah Stark, Hanns–Ulrich Marschall, Harm Jan Bogaard, Heather Maxwell, Helen Baxendale, Helen Hanson, Henning Gall, Hilary Longhurst, Hiva Fassihi, Horst Olschewski, 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 Clayton‐Smith, Joanna Pepke‐Żaba, Jodie Graham, John‐Paul 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, Kenneth G. C. Smith, 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 Vazquez‐Lopez, 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 Sadeghi‐Alavijeh, Paolo Gresele, Patrick Yong, Patrick Yu‐Wai‐Man, Paul Lyons, Paul Aurora, Paul A. Corris, Paul McAlinden, Paula Rayner-Matthews, Pavels Gordins, Peter Dixon, Peter Kelleher, Peter W. Collins, Petros Syrris, Philip Ancliff, Philip G. Griffiths, Philip Twiss, Ping Yu, Quinten Waisfisz, R. Andrés Floto, 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 Ross‐Russell, 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, Soo‐Mi 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
Bibliographic record
VenueScience · 2019
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicMitochondrial Function and Pathology
Canadian institutionsnot available
FundersSteno Diabetes Center AarhusNIHR Sheffield Biomedical Research CentreLeeds Biomedical Research CentreGreat Ormond Street Institute of Child HealthBiotechnology and Biological Sciences Research CouncilNIHR Cambridge Biomedical Research CentreNIHR BioResourceMedical Research CouncilServierNovo Nordisk FondenUniversity College London Hospitals NHS Foundation TrustNorthern Counties Kidney Research FundCambridge University HospitalsKU LeuvenUniversity of OxfordMoorfields Eye Hospital NHS Foundation TrustQueen's UniversityNovo NordiskQueen's University BelfastRosetrees TrustUniversity of NottinghamUK Research and InnovationSheffield Teaching Hospitals NHS Foundation TrustAstraZenecaEuropean CommissionChelsea and Westminster Hospital NHS Foundation TrustKing's College LondonKidney Research UKUniversity of CambridgeBritish Heart FoundationDirectorate for Biological SciencesNHS Blood and TransplantNational Institute for Health and Care ResearchSanofiBarts Health NHS TrustWellcomeKids Kidney ResearchLundbeckfondenUniversity College LondonImperial College Healthcare NHS TrustHorizon 2020 Framework ProgrammeRoyal Brompton and Harefield NHS Foundation TrustNottingham University Hospitals NHS TrustWellcome TrustCancer Research UKNIHR Oxford Biomedical Research CentreRoyal Free London NHS Foundation TrustUniversity Hospitals Birmingham NHS Foundation TrustBowel Cancer UKGreat Ormond Street Hospital for ChildrenNHS Greater Glasgow and ClydeSandwell and West Birmingham Hospitals NHS TrustMoorfields Eye CharityImperial College LondonPfizerNIHR Great Ormond Street Hospital Biomedical Research CentreEli Lilly and CompanyEvelyn TrustBristol-Myers Squibb
KeywordsHeteroplasmyMitochondrial DNABiologyGeneticsGermlineHuman mitochondrial geneticsGenomeSelection (genetic algorithm)Genetic diversitymtDNA control regionEvolutionary biologyHaplotypeAlleleGenePopulation
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.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.003
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
Opus teacher head0.012
GPT teacher head0.255
Teacher spread0.243 · how far apart the two teachers sit on this one work
Validation status
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".
Quick stats
Citations251
Published2019
Admission routes1
Has abstractyes