Cell
Volume 152, Issue 4, 14 February 2013, Pages 691-702
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Article
Modeling Recent Human Evolution in Mice by Expression of a Selected EDAR Variant

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Summary

An adaptive variant of the human Ectodysplasin receptor, EDARV370A, is one of the strongest candidates of recent positive selection from genome-wide scans. We have modeled EDAR370A in mice and characterized its phenotype and evolutionary origins in humans. Our computational analysis suggests the allele arose in central China approximately 30,000 years ago. Although EDAR370A has been associated with increased scalp hair thickness and changed tooth morphology in humans, its direct biological significance and potential adaptive role remain unclear. We generated a knockin mouse model and find that, as in humans, hair thickness is increased in EDAR370A mice. We identify new biological targets affected by the mutation, including mammary and eccrine glands. Building on these results, we find that EDAR370A is associated with an increased number of active eccrine glands in the Han Chinese. This interdisciplinary approach yields unique insight into the generation of adaptive variation among modern humans.

Highlights

► Selected East Asian EDAR allele, 370A, emerged in central China ∼30,000 years ago ► Hair, sweat, and mammary glands are altered in a 370A knockin mouse model ► The novel effect of 370A on mouse sweat gland density is recapitulated in humans

Cited by (0)

16

These authors contributed equally to this work

17

These authors contributed equally to this work and are cosenior authors

18

Present address: Max Planck-CAS Paul Gerson Unna Research Group on Dermatogenomics, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China

19

Present address: St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA

20

Present address: Department of Systems Biology Harvard Medical School, Boston, MA 02115, USA

21

Present address: Department of Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA

22

Present address: Department of Stem Cell Biology and Regenerative Medicine, Broad-CIRM Center, Keck School Of Medicine, University of Southern California, CA 90089, USA