PT - JOURNAL ARTICLE AU - Brenna M. Henn AU - Laura R. Botigué AU - Stephan Peischl AU - Isabelle Dupanloup AU - Mikhail Lipatov AU - Brian K. Maples AU - Alicia R. Martin AU - Shaila Musharoff AU - Howard Cann AU - Michael Snyder AU - Laurent Excoffier AU - Jeffrey M. Kidd AU - Carlos D. Bustamante TI - Distance from Sub-Saharan Africa Predicts Mutational Load in Diverse Human Genomes AID - 10.1101/019711 DP - 2015 Jan 01 TA - bioRxiv PG - 019711 4099 - http://biorxiv.org/content/early/2015/05/22/019711.short 4100 - http://biorxiv.org/content/early/2015/05/22/019711.full AB - The Out-of-Africa (OOA) dispersal ∼50,000 years 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 7 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.Data deposition Data have been deposited in the SRA [SRP036155] and in dbSNP. VCF files are freely available on the Henn Lab website: http://ecoevo.stonybrook.edu/hennlab/data/.