Genetic adaptation of skin pigmentation in highland Tibetans

doi:10.1073/pnas.2200421119

	Genetic adaptation of skin pigmentation in highland Tibetans
	Yang, Zhaohui 2,3,4; Bai, Caijuan 5; Pu, Youwei 3,4; Kong, Qinghong 6; Guo, Yongbo 2,7,8; Ouzhuluobu 5; Gengdeng 9; Liu, Xuyang 4; Zhao, Qi 4; Qiu, Zhichao 4
刊名	PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
	2022-09-26
卷号	119 期号:40 页码:11
关键词	high altitude Tibetan pigmentation adaptation
ISSN号	0027-8424
DOI	10.1073/pnas.2200421119
英文摘要	Strong ultraviolet (UV) radiation at high altitude imposes a serious selective pressure, which may induce skin pigmentation adaptation of indigenous populations. We con-ducted skin pigmentation phenotyping and genome-wide analysis of Tibetans in order to understand the underlying mechanism of adaptation to UV radiation. We observe that Tibetans have darker baseline skin color compared with lowland Han Chinese, as well as an improved tanning ability, suggesting a two-level adaptation to boost their melanin production. A genome-wide search for the responsible genes identifies GNPAT showing strong signals of positive selection in Tibetans. An enhancer mutation (rs75356281) located in GNPAT intron 2 is enriched in Tibetans (58%) but rare in other world populations (0 to 18%). The adaptive allele of rs75356281 is associated with darker skin in Tibetans and, under UVB treatment, it displays higher enhancer activities compared with the wild-type allele in in vitro luciferase assays. Transcriptome analyses of gene-edited cells clearly show that with UVB treatment, the adaptive variant of GNPAT promotes melanin synthesis, likely through the interactions of CAT and ACAA1 in peroxisomes with other pigmentation genes, and they act synergistically, leading to an improved tanning ability in Tibetans for UV protection.
资助项目	National Supercomputing Center in Zhengzhou ; National Natural Science Foundation of China[32070579] ; National Natural Science Foundation of China[31601016] ; National Natural Science Foundation of China[32070578] ; National Natural Science Foundation of China[91631306] ; National Natural Science Foundation of China[32030020] ; National Natural Science Foundation of China[32041008] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA20040102] ; Natural Science Foundation of Henan[222300420067] ; Provincial Key R&D Project of Tibetan Autonomous Region[XZ202201ZY0035G] ; Provincial Key R&D Project of Tibetan Autonomous Region[XZ202101ZY0009G] ; State Key Laboratory of Genetic Resources and Evolution[GREKF20-13] ; Shanghai Municipal Science and Technology Major Project[2017SHZDZX01] ; Innovation and Entrepreneurship Training Program for College Students[2021cxcy348]
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	NATL ACAD SCIENCES
WOS记录号	WOS:000898598800004
内容类型	期刊论文
源URL	[http://ir.amss.ac.cn/handle/2S8OKBNM/60476]
专题	中国科学院数学与系统科学研究院
通讯作者	Yang, Zhaohui; Qi, Xuebin; Su, Bing
作者单位	1.Fudan Univ, Sch Life Sci, Collaborat Innovat Ctr Genet & Dev, State Key Lab Genet Engn, Shanghai 200438, Peoples R China 2.Chinese Acad Sci, Kunming Inst Zool, State Key Lab Genet Resources & Evolut, Kunming 650223, Yunnan, Peoples R China 3.Zhengzhou Univ, Acad Med Sci, Zhengzhou 450052, Peoples R China 4.Kunming Univ Sci & Technol, Inst Primate Translat Med, Yunnan Key Lab Primate Biomed Res, Kunming 650500, Yunnan, Peoples R China 5.Tibetan Univ, Sch Med, High Altitude Med Res Ctr, Lhasa 850000, Peoples R China 6.Zunyi Med Univ, Guizhou Prov Coll Based Key Lab Tumor Prevent & T, Zunyi 563000, Guizhou, Peoples R China 7.Chinese Acad Sci, Ctr Excellence Anim Evolut & Genet, Kunming 650223, Yunnan, Peoples R China 8.Univ Chinese Acad Sci, Kunming Coll Life Sci, Beijing 100101, Peoples R China 9.Qinghai High Altitude Med Res Inst, Natl Key Lab High Altitude Med, Xining 810012, Peoples R China 10.Chinese Acad Sci, Acad Math & Syst Sci, Beijing 100190, Peoples R China
推荐引用方式 GB/T 7714	Yang, Zhaohui,Bai, Caijuan,Pu, Youwei,et al. Genetic adaptation of skin pigmentation in highland Tibetans[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2022,119(40):11.
APA	Yang, Zhaohui.,Bai, Caijuan.,Pu, Youwei.,Kong, Qinghong.,Guo, Yongbo.,...&Su, Bing.(2022).Genetic adaptation of skin pigmentation in highland Tibetans.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,119(40),11.
MLA	Yang, Zhaohui,et al."Genetic adaptation of skin pigmentation in highland Tibetans".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 119.40(2022):11.