Modeling Recent Human Evolution in Mice by Expression of a Selected EDAR Variant

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. [Display omitted] [Display omitted] ► 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 Engineering mice to express an allele of the human Ectodysplasin receptor, which originated in China approximately 30,000 years ago, alters hair thickness and mammary and sweat gland morphology, modeling effects that are also observed in human populations.