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Proc Natl Acad Sci U S A. 2016 Jan 26;113(4):E440-9. doi: 10.1073/pnas.1510805112. Epub 2015 Dec 28.

Distance from sub-Saharan Africa predicts mutational load in diverse human genomes.

Author information

1
Department of Ecology and Evolution, Stony Brook University, The State University of New York, Stony Brook, NY 11794; brenna.henn@stonybrook.edu cdbustam@stanford.edu.
2
Department of Ecology and Evolution, Stony Brook University, The State University of New York, Stony Brook, NY 11794;
3
Institute of Ecology and Evolution, University of Berne, 3012 Berne, Switzerland; Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland; Interfaculty Bioinformatics Unit, University of Berne, 3012 Berne, Switzerland;
4
Institute of Ecology and Evolution, University of Berne, 3012 Berne, Switzerland;
5
Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305;
6
Centre d'Etude du Polymorphisme Humain, Foundation Jean Dausset, 75010 Paris, France;
7
Institute of Ecology and Evolution, University of Berne, 3012 Berne, Switzerland; Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland;
8
Department of Human Genetics and Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI 48109.
9
Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305; brenna.henn@stonybrook.edu cdbustam@stanford.edu.

Abstract

The Out-of-Africa (OOA) dispersal ∼ 50,000 y ago is characterized by a series of founder events as modern humans expanded into multiple continents. Population genetics theory predicts an increase of mutational load in populations undergoing serial founder effects during range expansions. To test this hypothesis, we have sequenced full genomes and high-coverage exomes from seven geographically divergent human populations from Namibia, Congo, Algeria, Pakistan, Cambodia, Siberia, and Mexico. We find that individual genomes vary modestly in the overall number of predicted deleterious alleles. We show via spatially explicit simulations that the observed distribution of deleterious allele frequencies is consistent with the OOA dispersal, particularly under a model where deleterious mutations are recessive. We conclude that there is a strong signal of purifying selection at conserved genomic positions within Africa, but that many predicted deleterious mutations have evolved as if they were neutral during the expansion out of Africa. Under a model where selection is inversely related to dominance, we show that OOA populations are likely to have a higher mutation load due to increased allele frequencies of nearly neutral variants that are recessive or partially recessive.

KEYWORDS:

expansion load; founder effect; mutation; purifying selection; range expansion

PMID:
26712023
PMCID:
PMC4743782
DOI:
10.1073/pnas.1510805112
[Indexed for MEDLINE]
Free PMC Article

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