title: Modeling recent human evolution in mice by expression of a selected EDAR variant.
abstract: 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.
authors: Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
authors: Yana G
authors: YG
authors: Kamberov
authors: Sijia
authors: S
authors: Wang
authors: Jingze
authors: J
authors: Tan
authors: Pascale
authors: P
authors: Gerbault
authors: Abigail
authors: A
authors: Wark
authors: Longzhi
authors: L
authors: Tan
authors: Yajun
authors: Y
authors: Yang
authors: Shilin
authors: S
authors: Li
authors: Kun
authors: K
authors: Tang
authors: Hua
authors: H
authors: Chen
authors: Adam
authors: A
authors: Powell
authors: Yuval
authors: Y
authors: Itan
authors: Dorian
authors: D
authors: Fuller
authors: Jason
authors: J
authors: Lohmueller
authors: Junhao
authors: J
authors: Mao
authors: Asa
authors: A
authors: Schachar
authors: Madeline
authors: M
authors: Paymer
authors: Elizabeth
authors: E
authors: Hostetter
authors: Elizabeth
authors: E
authors: Byrne
authors: Melissa
authors: M
authors: Burnett
authors: Andrew P
authors: AP
authors: McMahon
authors: Mark G
authors: MG
authors: Thomas
authors: Daniel E
authors: DE
authors: Lieberman
authors: Li
authors: L
authors: Jin
authors: Clifford J
authors: CJ
authors: Tabin
authors: Bruce A
authors: BA
authors: Morgan
authors: Pardis C
authors: PC
authors: Sabeti
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D053339:Edar Receptor / Q000235:genetics*; D019143:Evolution, Molecular; D005088:Exocrine Glands / Q000502:physiology*; D055879:Gene Knock-In Techniques; D058685:Genetic Pleiotropy; D006197:Hair / Q000502:physiology*; D006239:Haplotypes; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D023421:Models, Animal; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D012535:Scalp / Q000502:physiology; D016415:Sequence Alignment; D055815:Young Adult
chemical_list: C506008:EDAR protein, human; D053339:Edar Receptor