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Nat Genet DOI:10.1038/ng.3186

No evidence that selection has been less effective at removing deleterious mutations in Europeans than in Africans.

Publication TypeJournal Article
Year of Publication2015
AuthorsDo, R, Balick, D, Li, H, Adzhubei, I, Sunyaev, S, Reich, D
JournalNat Genet
Volume47
Issue2
Pages126-31
Date Published2015 Feb
ISSN1546-1718
KeywordsAfrican Continental Ancestry Group, Amino Acid Substitution, Animals, Computer Simulation, European Continental Ancestry Group, Gene Frequency, Genetic Variation, Genetics, Population, Genome, Human, Humans, Models, Genetic, Mutation, Neanderthals, Selection, Genetic
Abstract

Non-African populations have experienced size reductions in the time since their split from West Africans, leading to the hypothesis that natural selection to remove weakly deleterious mutations has been less effective in the history of non-Africans. To test this hypothesis, we measured the per-genome accumulation of nonsynonymous substitutions across diverse pairs of populations. We find no evidence for a higher load of deleterious mutations in non-Africans. However, we detect significant differences among more divergent populations, as archaic Denisovans have accumulated nonsynonymous mutations faster than either modern humans or Neanderthals. To reconcile these findings with patterns that have been interpreted as evidence of the less effective removal of deleterious mutations in non-Africans than in West Africans, we use simulations to show that the observed patterns are not likely to reflect changes in the effectiveness of selection after the populations split but are instead likely to be driven by other population genetic factors.

URLhttp://dx.doi.org/10.1038/ng.3186
DOI10.1038/ng.3186
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/25581429?dopt=Abstract

Alternate JournalNat. Genet.
PubMed ID25581429
PubMed Central IDPMC4310772
Grant ListR01 GM078598 / GM / NIGMS NIH HHS / United States
R01MH101244 / MH / NIMH NIH HHS / United States
R01 GM100233 / GM / NIGMS NIH HHS / United States
R01 HG006399 / HG / NHGRI NIH HHS / United States
HG006399 / HG / NHGRI NIH HHS / United States
GM100233 / GM / NIGMS NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
R01 GM105857 / GM / NIGMS NIH HHS / United States
R01GM078598 / GM / NIGMS NIH HHS / United States
R01 MH101244 / MH / NIMH NIH HHS / United States