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

Cell. 2013 Feb 14;152(4):691-702. doi: 10.1016/j.cell.2013.01.016.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Amino Acid Sequence
  • Animals
  • Biological Evolution*
  • Edar Receptor / genetics*
  • Evolution, Molecular
  • Exocrine Glands / physiology*
  • Gene Knock-In Techniques
  • Genetic Pleiotropy
  • Hair / physiology*
  • Haplotypes
  • Humans
  • Mice*
  • Mice, Inbred C57BL
  • Middle Aged
  • Models, Animal*
  • Molecular Sequence Data
  • Polymorphism, Single Nucleotide
  • Scalp / physiology
  • Sequence Alignment
  • Young Adult


  • EDAR protein, human
  • Edar Receptor