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Proc Natl Acad Sci U S A. 2018 Dec 26;115(52):13324-13329. doi: 10.1073/pnas.1801948115. Epub 2018 Dec 10.

Rapid evolution of a skin-lightening allele in southern African KhoeSan.

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Department of Ecology and Evolution, State University of New York at Stony Brook, Stony Brook, NY 11794;
Department of Ecology and Evolution, State University of New York at Stony Brook, Stony Brook, NY 11794.
The School of Human Evolution and Social Change, Arizona State University, Tempe, AZ 85287.
Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114.
Program in Medical and Population Genetics, Broad Institute, Cambridge, MA 02141.
Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA 02141.
School of Medicine, Trinity College Dublin, Dublin 2, Ireland.
DST-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town 8000, South Africa.
Department of Genetics, Stanford University, Stanford, CA 94305.
Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045.
Department of Biostatistics and Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045.


Skin pigmentation is under strong directional selection in northern European and Asian populations. The indigenous KhoeSan populations of far southern Africa have lighter skin than other sub-Saharan African populations, potentially reflecting local adaptation to a region of Africa with reduced UV radiation. Here, we demonstrate that a canonical Eurasian skin pigmentation gene, SLC24A5, was introduced to southern Africa via recent migration and experienced strong adaptive evolution in the KhoeSan. To reconstruct the evolution of skin pigmentation, we collected phenotypes from over 400 ≠Khomani San and Nama individuals and high-throughput sequenced candidate pigmentation genes. The derived causal allele in SLC24A5, p.Ala111Thr, significantly lightens basal skin pigmentation in the KhoeSan and explains 8 to 15% of phenotypic variance in these populations. The frequency of this allele (33 to 53%) is far greater than expected from colonial period European gene flow; however, the most common derived haplotype is identical among European, eastern African, and KhoeSan individuals. Using four-population demographic simulations with selection, we show that the allele was introduced into the KhoeSan only 2,000 y ago via a back-to-Africa migration and then experienced a selective sweep (s = 0.04 to 0.05 in ≠Khomani and Nama). The SLC24A5 locus is both a rare example of intense, ongoing adaptation in very recent human history, as well as an adaptive gene flow at a pigmentation locus in humans.


Africa; KhoeSan; SLC24A5; adaptation; pigmentation

[Available on 2019-06-26]

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