Evolution Of The Skin-related Phenotypes In- Eurasian Populations And Mechanisms Of Multi-gene Interaction

About 50,000 to 100,000 years ago,modern human went out of Africa and migrated to the rest of the world.The phenotypic changes had adapted to meet the survival challenges of various new environments,especially the skin color.With the development of population genetics,the accumulation of phenotypic data and genomic data,studies have found that pigment genes are closely related to the adaptive evolution of the modern human populations.There stay a series of pigment synthesis-related genes associated with lighter skin color between East Asian and European populations.It has great differences in gene variations related to skin color adaptation between Eurasian with East Asian populations,which have evolved adaptive genetic feature independently to adapt with the different environmental pressures.The genetic variations of the pigment-synthesis-related genes associated with lighter skin color can only explain a small fraction of heritability.The skin color is a complex trait that cannot be explained by just a single gene or variant.The mixed population has a complexion genetic background which has mixed with the different genetic component underlined different adaptive evolution.The mixture can disrupt the genetic mutations structure of a stable population and show more phenotypic differences.The systematic study on mixed populations could fully understand the influence on genes of skin-related phenotypes,and the mechanism of the multi-gene interaction on human skin color.Kazak is an ideal of mixed population,which is mixed through European with East Asian populations,and it has a convergence evolution on skin color between these two populations.But there is almost no report on complexion of the Eurasian mixed populations and the genetic mechanism of the complexion phenotypic variation in them is still unclear.In this study,a genome-wide association analysis method was used to systematically analyze the correlation between pigment synthesis-related genes and complexion phenotypes of Kazak population.A statistical model of the phenotypic complexion with the genetic data of Xinjiang Kazak population was set up.Using genetic data from genomic chip,based on bioinformatics analysis software,5 SNP sites on two pigment genes OCA2 and SLC45A2 were detected.These SNPs significantly related to complexion variations in Kazak population.Further analysis of molecular evolution revealed that the missense mutation rs74653330(Ala?Thr),which is an amino acid substitution in the 14 th exon of the OCA2 gene,is very rare in modern human populations,but the alleles frequency is higher in Kazak.The other four loci rs28777,rs35407,exm2270197(rs35397)and rs250415 locate in the upstream region of the SLC45A2 gene.Four SNPs were received strong Darwinian selection in Kazak population and kept a complete LD map.Heritability analysis based on mutations found that genotype of 4 SNP sites were linkage and it had more contribution to the complexion variation than genotype of only a single SNP.The haplotype variations of this two gene linkage contributed more to the complexion variation than one single gene.It suggested that the complexion variation of Kazak population is due to the natural selection on several gene sites involved in pigment synthesis.Correlation analysis of Kazak population,which mixed through European with East Asian and they were proved to have a convergence evolution on skin color,could provide new evidences that phenotype of skin color is a complex trait controlled by multiple genes and multiple loci.