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Cell DOI:10.1016/j.cell.2013.01.016

Modeling recent human evolution in mice by expression of a selected EDAR variant.

Publication TypeJournal Article
Year of Publication2013
AuthorsKamberov, YG, Wang, S, Tan, J, Gerbault, P, Wark, A, Tan, L, Yang, Y, Li, S, Tang, K, Chen, H, Powell, A, Itan, Y, Fuller, D, Lohmueller, J, Mao, J, Schachar, A, Paymer, M, Hostetter, E, Byrne, E, Burnett, M, McMahon, AP, Thomas, MG, Lieberman, DE, Jin, L, Tabin, CJ, Morgan, BA, Sabeti, PC
Date Published2013 Feb 14
KeywordsAdolescent, Adult, Amino Acid Sequence, Animals, Biological Evolution, Edar Receptor, Evolution, Molecular, Exocrine Glands, Gene Knock-In Techniques, Genetic Pleiotropy, Hair, Haplotypes, Humans, Mice, Mice, Inbred C57BL, Middle Aged, Models, Animal, Molecular Sequence Data, Polymorphism, Single Nucleotide, Scalp, Sequence Alignment, Young Adult

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.


Alternate JournalCell
PubMed ID23415220
PubMed Central IDPMC3575602
Grant List1DP2OD006514-01 / OD / NIH HHS / United States
R01 AR055256 / AR / NIAMS NIH HHS / United States
R37 HD032443 / HD / NICHD NIH HHS / United States
DP2 OD006514 / OD / NIH HHS / United States
R37 054364 / / PHS HHS / United States