Distance from Sub-Saharan Africa Predicts Mutational Load in Diverse Human Genomes

Henn, Brenna M.; Botigué, Laura R.; Peischl, Stephan; Duperret, Isabelle; Lipatov, Mikhail; Maples, Brian K.; Martin, Alicia R.; Musharoff, Shaila; Cann, Howard; Snyder, Michael P.; Excoffier, Laurent; Kidd, Jeffrey M.; Bustamante, Carlos D. (2016). Distance from Sub-Saharan Africa Predicts Mutational Load in Diverse Human Genomes. Proceedings of the National Academy of Sciences of the United States of America - PNAS, 113(4), E440-E449. National Academy of Sciences NAS 10.1073/pnas.1510805112

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Department of Biology > Institute of Ecology and Evolution (IEE) > Population Genetics

UniBE Contributor:

Peischl, Stephan; Duperret, Isabelle and Excoffier, Laurent

Subjects:

500 Science > 570 Life sciences; biology

ISSN:

0027-8424

Publisher:

National Academy of Sciences NAS

Language:

English

Submitter:

Isabelle Duperret

Date Deposited:

04 May 2016 11:11

Last Modified:

04 May 2016 11:11

Publisher DOI:

10.1073/pnas.1510805112

PubMed ID:

26712023

BORIS DOI:

10.7892/boris.79894

URI:

https://boris.unibe.ch/id/eprint/79894

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