Weakened tanning ability is an important mechanism for evolutionary skin lightening in East Asians  

作　　者：Youwei Pu Siyu Pu Yanyan Chen Qinghong Kong Xuyang Liu Qi Zhao Ke Xu Jiuming Liu Mengyuan Li Xiaoyu Xu Xiaoyang Qiao Bing Su Jing Chen Zhaohui Yang 

机构地区：[1]Tianjian Laboratory of Advanced Biomedical Sciences,Academy of Medical Science,Zhengzhou University,Zhengzhou,Henan 450052,China [2]Department of Pediatric Surgery and Laboratory of Pediatric Surgery,West China Hospital,Sichuan University,Chengdu,Sichuan 610041,China [3]Guizhou Provincial College-based Key Lab for Tumor Prevention and Treatment with Distinctive Medicines,Zunyi Medical University,Zunyi,Guizhou 563000,China [4]Yunnan Key Laboratory of Primate Biomedical Research,Institute of Primate Translational Medicine,Kunming University of Science and Technology,Kunming,Yunnan 650500,China [5]State Key Laboratory of Genetic Resources and Evolution,Kunming Institute of Zoology,Chinese Academy of Sciences,Kunming,Yunnan 650223,China [6]Center for Excellence in Animal Evolution and Genetics,Chinese Academy of Sciences,Kunming,Yunnan 650223,China

出　　处：《Journal of Genetics and Genomics》2024年第7期703-713,共11页遗传学报（英文版）

基　　金：supported by the National Natural Science Foundation of China(32070579 and 32370664 to Z.Y.,31871449 and 32170813 to J.C.);the Natural Science Foundation of Henan(222300420067 to Z.Y.);State Key Laboratory of Genetic Resources and Evolution Grant(GREKF20-13 to Z.Y);Innovation and Entrepreneurship Training Program(2022cxcy568,2022cxcy717 and 2023cxcy475 to Z.Y.);the 1.3·5 project for disciplines of excellence of West China Hospital,Sichuan University(ZYGD23026 and 2024HXFH035);Science and Technologyy Department of Sichuan province(2024NSFSC0651).

摘　　要：The evolution of light-skin pigmentation among Eurasians is considered as an adaptation to the high-latitude environments.East Asians are ideal populations for studying skin color evolution because of the complex environment of East Asia.Here,we report a strong selection signal for the pigmentation gene phenylalanine hydroxylase(PAH)in light-skinned Han Chinese individuals.The intron mutation rs10778203 in PAH is enriched in East Asians and is significantly associated with skin color of the back of the hand in Han Chinese males(P<0.05).In vitro luciferase and transcription factor binding assays show that the ancestral allele of rs10778203 could bind to SMAD2 and has a significant enhancer activity for PAH.However,the derived T allele(the major allele in East Asians)of rs10778203 decreases the binding activity of transcription factors and enhancer activity.Meanwhile,the derived T allele of rs10778203 shows a weaker ultraviolet radiation response in A375 cells and zebrafish embryos.Furthermore,rs10778203 decreases melanin production in transgenic zebrafish embryos after ultraviolet B(UVB)treatment.Collectively,PAH is a potential pigmentation gene that regulates skin tanning ability.Natural selection has enriched the adaptive allele,resulting in weakened tanning ability in East Asians,suggesting a unique genetic mechanism for evolutionary skin lightening in East Asians.

关 键 词：East Asians PAH Skin pigmentation Natural selection Genetic adaptation 

分 类 号：Q987[生物学—遗传学]