title: Neanderthal origin of the haplotypes carrying the functional variant Val92Met in the MC1R in modern humans.
abstract: Skin color is one of the most visible and important phenotypes of modern humans. Melanocyte-stimulating hormone and its receptor played an important role in regulating skin color. In this article, we present evidence of Neanderthal introgression encompassing the melanocyte-stimulating hormone receptor gene MC1R. The haplotypes from Neanderthal introgression diverged with the Altai Neanderthal 103.3 ka, which postdates the anatomically modern human-Neanderthal divergence. We further discovered that all of the putative Neanderthal introgressive haplotypes carry the Val92Met variant, a loss-of-function variant in MC1R that is associated with multiple dermatological traits including skin color and photoaging. Frequency of this Neanderthal introgression is low in Europeans (∼5%), moderate in continental East Asians (∼30%), and high in Taiwanese aborigines (60-70%). As the putative Neanderthal introgressive haplotypes carry a loss-of-function variant that could alter the function of MC1R and is associated with multiple traits related to skin color, we speculate that the Neanderthal introgression may have played an important role in the local adaptation of Eurasians to sunlight intensity.
authors.affiliation: State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: Qiliang
authors.initials: Q
authors.lastname: Ding
authors.affiliation: State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Hu
authors.affiliation: CAS-MPG Partner Institute for Computational Biology, Shanghai Institute for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai, China.
authors.forename: Shuhua
authors.initials: S
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: Chuan-Chao
authors.initials: CC
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: Ruyue
authors.initials: R
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: Shi
authors.initials: S
authors.lastname: Yan
authors.affiliation: State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: Jiucun
authors.initials: J
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, ChinaCAS-MPG Partner Institute for Computational Biology, Shanghai Institute for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai, China lijin.fudan@gmail.com.
authors.forename: Li
authors.initials: L
authors.lastname: Jin
mesh_terms: D000818:Animals; D044466:Asian People / Q000208:ethnology / Q000235:genetics; D005075:Biological Evolution; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D008715:Methionine / Q000378:metabolism*; D059125:Neanderthals / Q000235:genetics*; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics*; D015595:Skin Aging / Q000235:genetics; D014633:Valine / Q000378:metabolism*; D044465:White People / Q000235:genetics
chemical_list: D044102:Receptor, Melanocortin, Type 1; D008715:Methionine; D014633:Valine
keywords: MC1R; Neanderthal; introgression; local adaptation; skin color