title: A Genetic Mechanism for Convergent Skin Lightening during Recent Human Evolution.
abstract: Skin lightening among Eurasians is thought to have been a convergence occurring independently in Europe and East Asia as an adaptation to high latitude environments. Among Europeans, several genes responsible for such lightening have been found, but the information available for East Asians is much more limited. Here, a genome-wide comparison between dark-skinned Africans and Austro-Asiatic speaking aborigines and light-skinned northern Han Chinese identified the pigmentation gene OCA2, showing unusually deep allelic divergence between these groups. An amino acid substitution (His615Arg) of OCA2 prevalent in most East Asian populations-but absent in Africans and Europeans-was significantly associated with skin lightening among northern Han Chinese. Further transgenic and targeted gene modification analyses of zebrafish and mouse both exhibited the phenotypic effect of the OCA2 variant manifesting decreased melanin production. These results indicate that OCA2 plays an important role in the convergent skin lightening of East Asians during recent human evolution.
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing, China Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan, China sub@mail.kiz.ac.cn mengam@mail.tsinghua.edu.cn shihong@kbimed.com.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX sub@mail.kiz.ac.cn mengam@mail.tsinghua.edu.cn shihong@kbimed.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhong
authors.affiliation: State Key Laboratory of Membrane Biology, School of Life Sciences, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, China sub@mail.kiz.ac.cn mengam@mail.tsinghua.edu.cn shihong@kbimed.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China sub@mail.kiz.ac.cn mengam@mail.tsinghua.edu.cn shihong@kbimed.com.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China sub@mail.kiz.ac.cn mengam@mail.tsinghua.edu.cn shihong@kbimed.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing, China sub@mail.kiz.ac.cn mengam@mail.tsinghua.edu.cn shihong@kbimed.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Luo
authors.affiliation: Max Planck Independent Research Group on Population Genomics, Chinese Academy of Sciences and Max Planck Society (CAS-MPG) Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China sub@mail.kiz.ac.cn mengam@mail.tsinghua.edu.cn shihong@kbimed.com.
authors.forename: Shuhua
authors.initials: S
authors.lastname: Xu
authors.affiliation: Center for Computational Genomics, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China sub@mail.kiz.ac.cn mengam@mail.tsinghua.edu.cn shihong@kbimed.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Chen
authors.affiliation: Max Planck Independent Research Group on Population Genomics, Chinese Academy of Sciences and Max Planck Society (CAS-MPG) Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China sub@mail.kiz.ac.cn mengam@mail.tsinghua.edu.cn shihong@kbimed.com.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Lu
authors.affiliation: College of Life Science, Liaoning Normal University, Dalian, China sub@mail.kiz.ac.cn mengam@mail.tsinghua.edu.cn shihong@kbimed.com.
authors.forename: Yinglun
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Urology, First Affiliated Hospital of Kunming Medical University, Kunming, China sub@mail.kiz.ac.cn mengam@mail.tsinghua.edu.cn shihong@kbimed.com.
authors.forename: Jinkun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Urology, First Affiliated Hospital of Kunming Medical University, Kunming, China sub@mail.kiz.ac.cn mengam@mail.tsinghua.edu.cn shihong@kbimed.com.
authors.forename: Lijie
authors.initials: L
authors.lastname: Fu
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China sub@mail.kiz.ac.cn mengam@mail.tsinghua.edu.cn shihong@kbimed.com.
authors.forename: Xuebin
authors.initials: X
authors.lastname: Qi
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China sub@mail.kiz.ac.cn mengam@mail.tsinghua.edu.cn shihong@kbimed.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China sub@mail.kiz.ac.cn mengam@mail.tsinghua.edu.cn shihong@kbimed.com.
authors.forename: Kun
authors.initials: K
authors.lastname: Xiang
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing, China sub@mail.kiz.ac.cn mengam@mail.tsinghua.edu.cn shihong@kbimed.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China sub@mail.kiz.ac.cn mengam@mail.tsinghua.edu.cn shihong@kbimed.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China sub@mail.kiz.ac.cn mengam@mail.tsinghua.edu.cn shihong@kbimed.com.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China sub@mail.kiz.ac.cn mengam@mail.tsinghua.edu.cn shihong@kbimed.com.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China sub@mail.kiz.ac.cn mengam@mail.tsinghua.edu.cn shihong@kbimed.com.
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China sub@mail.kiz.ac.cn mengam@mail.tsinghua.edu.cn shihong@kbimed.com.
authors.forename: Shiyu
authors.initials: S
authors.lastname: Liao
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China sub@mail.kiz.ac.cn mengam@mail.tsinghua.edu.cn shihong@kbimed.com.
authors.forename: Yingmei
authors.initials: Y
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Membrane Biology, School of Life Sciences, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, China sub@mail.kiz.ac.cn mengam@mail.tsinghua.edu.cn shihong@kbimed.com.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: BGI-Shenzhen, Shenzhen, China Department of Biology, University of Copenhagen, Copenhagen, Denmark sub@mail.kiz.ac.cn mengam@mail.tsinghua.edu.cn shihong@kbimed.com.
authors.forename: Xiaosen
authors.initials: X
authors.lastname: Guo
authors.affiliation: BGI-Shenzhen, Shenzhen, China sub@mail.kiz.ac.cn mengam@mail.tsinghua.edu.cn shihong@kbimed.com.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Dong
authors.affiliation: BGI-Shenzhen, Shenzhen, China sub@mail.kiz.ac.cn mengam@mail.tsinghua.edu.cn shihong@kbimed.com.
authors.forename: Fan
authors.initials: F
authors.lastname: Liang
authors.affiliation: BGI-Shenzhen, Shenzhen, China Department of Biology, University of Copenhagen, Copenhagen, Denmark sub@mail.kiz.ac.cn mengam@mail.tsinghua.edu.cn shihong@kbimed.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China sub@mail.kiz.ac.cn mengam@mail.tsinghua.edu.cn shihong@kbimed.com.
authors.forename: Andrew
authors.initials: A
authors.lastname: Willden
authors.affiliation: Geography and Land Management, Royal University of Phnom Penh, Phnom Penh, Kingdom of Cambodia sub@mail.kiz.ac.cn mengam@mail.tsinghua.edu.cn shihong@kbimed.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Seang Aun
authors.affiliation: Geography and Land Management, Royal University of Phnom Penh, Phnom Penh, Kingdom of Cambodia sub@mail.kiz.ac.cn mengam@mail.tsinghua.edu.cn shihong@kbimed.com.
authors.forename: Bun
authors.initials: B
authors.lastname: Serey
authors.affiliation: Geography and Land Management, Royal University of Phnom Penh, Phnom Penh, Kingdom of Cambodia sub@mail.kiz.ac.cn mengam@mail.tsinghua.edu.cn shihong@kbimed.com.
authors.forename: Tuot
authors.initials: T
authors.lastname: Sovannary
authors.affiliation: Geography and Land Management, Royal University of Phnom Penh, Phnom Penh, Kingdom of Cambodia sub@mail.kiz.ac.cn mengam@mail.tsinghua.edu.cn shihong@kbimed.com.
authors.forename: Long
authors.initials: L
authors.lastname: Bunnath
authors.affiliation: Capacity Development Facilitator for Handicap International Federation and Freelance Researcher, Battambang, Kingdom of Cambodia sub@mail.kiz.ac.cn mengam@mail.tsinghua.edu.cn shihong@kbimed.com.
authors.forename: Ham
authors.initials: H
authors.lastname: Samnom
authors.affiliation: Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX sub@mail.kiz.ac.cn mengam@mail.tsinghua.edu.cn shihong@kbimed.com.
authors.forename: Graeme
authors.initials: G
authors.lastname: Mardon
authors.affiliation: College of Life Science, Liaoning Normal University, Dalian, China sub@mail.kiz.ac.cn mengam@mail.tsinghua.edu.cn shihong@kbimed.com.
authors.forename: Qingwei
authors.initials: Q
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authors.affiliation: State Key Laboratory of Membrane Biology, School of Life Sciences, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, China sub@mail.kiz.ac.cn mengam@mail.tsinghua.edu.cn shihong@kbimed.com.
authors.forename: Anming
authors.initials: A
authors.lastname: Meng
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan, China sub@mail.kiz.ac.cn mengam@mail.tsinghua.edu.cn shihong@kbimed.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China sub@mail.kiz.ac.cn mengam@mail.tsinghua.edu.cn shihong@kbimed.com.
authors.forename: Bing
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mesh_terms: D000293:Adolescent; D000483:Alleles; D019943:Amino Acid Substitution; D044466:Asian People / Q000235:genetics*; D005075:Biological Evolution; D044383:Black People / Q000235:genetics; D002648:Child; D005006:Ethnicity / Q000235:genetics; D019143:Evolution, Molecular; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies / Q000379:methods; D014644:Genetic Variation; D005828:Genetics, Population / Q000379:methods; D006239:Haplotypes; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D012641:Selection, Genetic; D012880:Skin Pigmentation / Q000235:genetics* / Q000502:physiology; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D026901:Membrane Transport Proteins; C489600:OCA2 protein, human
keywords: East Asians; OCA2; adaptation; natural selection; pigmentation genes; skin lightening