latitudinal clines of the human vitamin d receptor and skin color genes

latitudinal clines of the human vitamin d receptor and skin color genes

;Dov Tiosano;Laura Audi;Sharlee Climer;Weixiong Zhang;Alan R. Templeton;Monica Fernández-Cancio;Ruth Gershoni-Baruch;José Miguel Sánchez-Muro;Mohamed El Kholy;Zèev Hochberg
separation and purification technology 2016 Vol. 6 pp. 1251-1266
202
tiosano2016g3:latitudinal

Abstract

The well-documented latitudinal clines of genes affecting human skin color presumably arise from the need for protection from intense ultraviolet radiation (UVR) vs. the need to use UVR for vitamin D synthesis. Sampling 751 subjects from a broad range of latitudes and skin colors, we investigated possible multilocus correlated adaptation of skin color genes with the vitamin D receptor gene (VDR), using a vector correlation metric and network method called BlocBuster. We discovered two multilocus networks involving VDR promoter and skin color genes that display strong latitudinal clines as multilocus networks, even though many of their single gene components do not. Considered one by one, the VDR components of these networks show diverse patterns: no cline, a weak declining latitudinal cline outside of Africa, and a strong in- vs. out-of-Africa frequency pattern. We confirmed these results with independent data from HapMap. Standard linkage disequilibrium analyses did not detect these networks. We applied BlocBuster across the entire genome, showing that our networks are significant outliers for interchromosomal disequilibrium that overlap with environmental variation relevant to the genes’ functions. These results suggest that these multilocus correlations most likely arose from a combination of parallel selective responses to a common environmental variable and coadaptation, given the known Mendelian epistasis among VDR and the skin color genes.

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