RT Journal Article
SR Electronic
T1 Distance from Sub-Saharan Africa Predicts Mutational Load in Diverse Human Genomes
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 019711
DO 10.1101/019711
A1 Brenna M. Henn
A1 Laura R. Botigué
A1 Stephan Peischl
A1 Isabelle Dupanloup
A1 Mikhail Lipatov
A1 Brian K. Maples
A1 Alicia R. Martin
A1 Shaila Musharoff
A1 Howard Cann
A1 Michael Snyder
A1 Laurent Excoffier
A1 Jeffrey M. Kidd
A1 Carlos D. Bustamante
YR 2015
UL http://biorxiv.org/content/early/2015/10/23/019711.abstract
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.