The 84th Annual Meeting of the American Association of Physical Anthropologists (2015)


The Out of Africa expansion affected accumulation of deleterious alleles in human genomes

LAURA R. BOTIGUE1, BRENNA M. HENN1, STEPHAN PEISCHL2, ISABELLE DUPANLOUP2, MIKHAIL LIPATOV1, BRIAN K. MAPLES3, ALICIA R. MARTIN3, MC YEE3, HOWARD CANN4, MICHAEL SNYDER3, LAURENT EXCOFFIER2, JEFFREY M. KIDD5 and CARLOS D. BUSTAMANTE3.

1Department of Ecology and Evolution, Stony Brook, 2Institute of Ecology and Evolution, University of Berne, 3Department of Genetics, Stanford University, 4Foundation Jean Dausset, Centre d'Etude du Polymorphisme Humain, 5Department of Human Genetics, Universitiy of Michigan

March 26, 2015 1:00, Lindbergh Add to calendar

The Out of Africa dispersal ~50,000 years ago is characterized by a pattern of serial founder effects as modern humans expanded into multiple continents. From population genetic theory, we expect an increase in the proportion of deleterious alleles, and therefore mutational load, in populations that have undergone a combination of bottlenecks and expansion. To test this hypothesis, we have sequenced full genomes and high-coverage exomes from over 50 individuals from 7 human populations, establishing a picture of genomic diversity in geographically divergent groups from Namibia, Congo, Algeria, Pakistan, Cambodia, Siberia and Mexico. We find that individuals vary in the number of predicted large effect deleterious alleles they carry. We use a model of mutational load and incorporate different selection coefficients and vary the deleterious effect of heterozygotes (dominance). We estimate an increased load in populations outside of Africa particularly if most deleterious variants are recessive. We show via spatially explicit simulations that the distributions of deleterious alleles are consistent with the Out of Africa dispersal.

We conclude that purifying selection historically differed in its efficacy among populations. We conclude that unless under extreme selection, most deleterious mutations in genic regions have evolved neutrally in non-African populations.

NIH grant 3R01HG003229 NIH grant DP5OD009154 Swiss grant SNSF 31003A-143393 Catalan grant BP_A 00497