Germline selection shapes human mitochondrial DNA diversity
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 mater...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Published: |
American Association for the Advancement of Science
2019
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| _version_ | 1826284106869112832 |
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| author | 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 NIHR BioResource–Rare Diseases 100,000 Genomes Project–Rare Diseases Pilot Ashford, S Penkett, CJ Stirrups, KE Rendon, A Ouwehand, WH Bradley, JR Raymond, FL Caulfield, M Turro, E Chinnery, PF |
| author_facet | 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 NIHR BioResource–Rare Diseases 100,000 Genomes Project–Rare Diseases Pilot Ashford, S Penkett, CJ Stirrups, KE Rendon, A Ouwehand, WH Bradley, JR Raymond, FL Caulfield, M Turro, E Chinnery, PF |
| author_sort | Wei, W |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T01:08:53Z |
| format | Journal article |
| id | oxford-uuid:8c4c93aa-8c16-456b-8346-d05af30b4b1b |
| institution | University of Oxford |
| last_indexed | 2024-03-07T01:08:53Z |
| publishDate | 2019 |
| publisher | American Association for the Advancement of Science |
| record_format | dspace |
| spelling | oxford-uuid:8c4c93aa-8c16-456b-8346-d05af30b4b1b2022-03-26T22:43:51ZGermline selection shapes human mitochondrial DNA diversityJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:8c4c93aa-8c16-456b-8346-d05af30b4b1bSymplectic Elements at OxfordAmerican Association for the Advancement of Science2019Wei, WTuna, SKeogh, MJSmith, KRAitman, TJBeales, PLBennett, DLGale, DPBitner-Glindzicz, MAKBlack, GCBrennan, PElliott, PFlinter, FAFloto, RAHoulden, HIrving, MKoziell, AMaher, ERMarkus, HSMorrell, NWNewman, WGRoberts, ISayer, JASmith, KGCTaylor, JCWatkins, HWebster, ARWilkie, AOMWilliamson, CNIHR BioResource–Rare Diseases100,000 Genomes Project–Rare Diseases PilotAshford, SPenkett, CJStirrups, KERendon, AOuwehand, WHBradley, JRRaymond, FLCaulfield, MTurro, EChinnery, PFApproximately 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. |
| spellingShingle | 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 NIHR BioResource–Rare Diseases 100,000 Genomes Project–Rare Diseases Pilot Ashford, S Penkett, CJ Stirrups, KE Rendon, A Ouwehand, WH Bradley, JR Raymond, FL Caulfield, M Turro, E Chinnery, PF Germline selection shapes human mitochondrial DNA diversity |
| title | Germline selection shapes human mitochondrial DNA diversity |
| title_full | Germline selection shapes human mitochondrial DNA diversity |
| title_fullStr | Germline selection shapes human mitochondrial DNA diversity |
| title_full_unstemmed | Germline selection shapes human mitochondrial DNA diversity |
| title_short | Germline selection shapes human mitochondrial DNA diversity |
| title_sort | germline selection shapes human mitochondrial dna diversity |
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