TY - JOUR
T1 - Modeling recent human evolution in mice by expression of a selected EDAR variant
AU - Kamberov, Yana G.
AU - Wang, Sijia
AU - Tan, Jingze
AU - Gerbault, Pascale
AU - Wark, Abigail
AU - Tan, Longzhi
AU - Yang, Yajun
AU - Li, Shilin
AU - Tang, Kun
AU - Chen, Hua
AU - Powell, Adam
AU - Itan, Yuval
AU - Fuller, Dorian
AU - Lohmueller, Jason
AU - Mao, Junhao
AU - Schachar, Asa
AU - Paymer, Madeline
AU - Hostetter, Elizabeth
AU - Byrne, Elizabeth
AU - Burnett, Melissa
AU - McMahon, Andrew P.
AU - Thomas, Mark G.
AU - Lieberman, Daniel E.
AU - Jin, Li
AU - Tabin, Clifford J.
AU - Morgan, Bruce A.
AU - Sabeti, Pardis C.
N1 - Funding Information:
This project was funded by a grant from the Harvard University Science and Engineering Committee Seed Fund for Interdisciplinary Science to CJT, PCS, BAM and DEL; a Packard Foundation Fellowship in Science and Engineering and an NIH Innovator Award 1DP2OD006514-01 to PCS; a BIRT Award AR055256-04S1 from NIAMS to BAM; an NIH grant R37 HD032443 to CJT; and funding from the American School of Prehistoric Research to DEL. Human association study work was additionally supported by NSFC 30890034; MOST 2011BAI09B00; MOH 201002007 to LJ. YI was funded by an AXA Research Fund postdoctoral fellowship and PG by the LeCHE Marie Curie FP7 framework. Work in APM’s laboratory was supported by an NIH R37 054364 grant. We acknowledge the UCL Legion High Performance Computing Facility and support services and thank O. Bar Yosef, C. Zhao, E. Rohling, S. Schaffner, L.Gaffney, C. Edwards, J. Vitti, S.Tabrizi and A.Tariela for feedback on the manuscript and A.Carpenter, C. Wählby, and M. Morgan for data analysis help. The authors declare no conflict of interest.
PY - 2013/2/14
Y1 - 2013/2/14
N2 - 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. PaperFlick:
AB - 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. PaperFlick:
UR - https://www.scopus.com/pages/publications/84874048561
U2 - 10.1016/j.cell.2013.01.016
DO - 10.1016/j.cell.2013.01.016
M3 - Article
C2 - 23415220
AN - SCOPUS:84874048561
SN - 0092-8674
VL - 152
SP - 691
EP - 702
JO - Cell
JF - Cell
IS - 4
ER -