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Record W2945018607 · doi:10.1126/science.aau6520

Germline selection shapes human mitochondrial DNA diversity

2019· article· en· W2945018607 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

fundA Canadian funder is recorded on the work.
no affNo Canadian affiliation: this work is invisible to an affiliation-only frame.
No Canadian affiliation. An affiliation-only frame, the usual design, would never have seen this work. It is one of the works that make the case for inverting the frame.

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

fetched live from OpenAlex

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.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.113
Threshold uncertainty score0.387

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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 statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it