title: Distance from sub-Saharan Africa predicts mutational load in diverse human genomes.
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.
authors.affiliation: 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.
authors.forename: Brenna M
authors.initials: BM
authors.lastname: Henn
authors.affiliation: Department of Ecology and Evolution, Stony Brook University, The State University of New York, Stony Brook, NY 11794;
authors.forename: Laura R
authors.initials: LR
authors.lastname: Botigué
authors.affiliation: 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;
authors.forename: Stephan
authors.initials: S
authors.lastname: Peischl
authors.affiliation: Institute of Ecology and Evolution, University of Berne, 3012 Berne, Switzerland;
authors.forename: Isabelle
authors.initials: I
authors.lastname: Dupanloup
authors.affiliation: Department of Ecology and Evolution, Stony Brook University, The State University of New York, Stony Brook, NY 11794;
authors.forename: Mikhail
authors.initials: M
authors.lastname: Lipatov
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305;
authors.forename: Brian K
authors.initials: BK
authors.lastname: Maples
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305;
authors.forename: Alicia R
authors.initials: AR
authors.lastname: Martin
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305;
authors.forename: Shaila
authors.initials: S
authors.lastname: Musharoff
authors.affiliation: Centre d'Etude du Polymorphisme Humain, Foundation Jean Dausset, 75010 Paris, France;
authors.forename: Howard
authors.initials: H
authors.lastname: Cann
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305;
authors.forename: Michael P
authors.initials: MP
authors.lastname: Snyder
authors.affiliation: Institute of Ecology and Evolution, University of Berne, 3012 Berne, Switzerland; Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland;
authors.forename: Laurent
authors.initials: L
authors.lastname: Excoffier
authors.affiliation: Department of Human Genetics and Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI 48109.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Kidd
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305; brenna.henn@stonybrook.edu cdbustam@stanford.edu.
authors.forename: Carlos D
authors.initials: CD
authors.lastname: Bustamante
mesh_terms: D017954:Africa South of the Sahara; D000483:Alleles; D000818:Animals; D044466:Asian People / Q000235:genetics; D044383:Black People / Q000235:genetics; D003198:Computer Simulation; D017124:Conserved Sequence; D005006:Ethnicity / Q000235:genetics*; D019143:Evolution, Molecular; D018703:Founder Effect; D051456:Gene Flow; D030342:Genetic Diseases, Inborn / Q000235:genetics; D040961:Genetic Drift; D015894:Genome, Human; D005838:Genotype; D006702:Homing Behavior; D063426:Human Migration; D006801:Humans; D007197:Indians, Central American / Q000235:genetics; D008957:Models, Genetic; D009154:Mutation; D012641:Selection, Genetic
keywords: expansion load; founder effect; mutation; purifying selection; range expansion