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 envi...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.展开更多
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.)+3 种基金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).
文摘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.
