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

Youwei Pu ¹Siyu Pu ²Yanyan Chen ¹Qinghong Kong ³Xuyang Liu ¹Qi Zhao ⁴Ke Xu ¹Jiuming Liu ¹Mengyuan Li ¹Xiaoyu Xu ¹Xiaoyang Qiao ¹Bing Su ⁵Jing Chen ²Zhaohui Yang¹

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作者信息

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;Center for Excellence in Animal Evolution and Genetics,Chinese Academy of Sciences,Kunming,Yunnan 650223,China
折叠

Abstract

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.

Key words

East Asians/PAH/Skin pigmentation/Natural selection/Genetic adaptation

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基金项目

National Supercomputing Center in Zhengzhou()

National Natural Science Foundation of China(32070579)

National Natural Science Foundation of China(32370664)

National Natural Science Foundation of China(31871449)

National Natural Science Foundation of China(32170813)

Natural Science Foundation of Henan(222300420067)

State Key Laboratory of Genetic Resources and Evolution Grant(GREKF20-13)

Innovation and Entrepreneurship Training Program(2022cxcy568)

Innovation and Entrepreneurship Training Program(2022cxcy717)

Innovation and Entrepreneurship Training Program(2023cxcy475)

1-3-5 project for disciplines of excellence of West China Hospital,Sichuan University(ZYGD23026)

1-3-5 project for disciplines of excellence of West China Hospital,Sichuan University(2024HXFH035)

Science and Technology Department of Sichuan province(2024NSFSC0651)

出版年

2024

遗传学报

中国遗传学会中国科学院遗传与发育生物学研究所

遗传学报

CSTPCDCSCD

影响因子：0.821

ISSN：1673-8527

参考文献量68

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