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Nat Genet. 2015 Feb;47(2):126-31. doi: 10.1038/ng.3186. Epub 2015 Jan 12.

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

Author information

1
1] Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA. [2] Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
2
1] Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA. [2] Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
3
Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
4
1] Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA. [2] Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA. [3] Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts, USA.

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.

PMID:
25581429
PMCID:
PMC4310772
DOI:
10.1038/ng.3186
[Indexed for MEDLINE]
Free PMC Article
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