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Latitudinal clines of the human vitamin D receptor and skin color genes

Tiosano, D
; 
Audi, L
; 
Climer, S
; 
Zhang, W
; 
Templeton, AR
; 
Fernández-Cancio, M
; 
Gershoni-Baruch, R
; 
Sánchez-Muro, JM
; 
El Kholy, M
; 
Hochberg, Z
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Journal Article
Date
2016-05-01
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Subject
adaptation
 epistasis
 linkage disequilibrium
 network analysis
 skin color
 vitamin D
 Adaptation, Biological
 Alleles
 Altitude
 Computational Biology
 Epistasis, Genetic
 Gene Frequency
 Gene Regulatory Networks
 Gene-Environment Interaction
 Genetic Linkage
 Genome, Human
 Genomics
 Genotype
 Humans
 Linkage Disequilibrium
 Polymorphism, Single Nucleotide
 Receptors, Calcitriol
 Skin Pigmentation
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http://hdl.handle.net/20.500.12613/5584
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Latitudinal Clines of the Human Vitamin D Receptor and Skin Color Genes.pdf
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DOI
10.1534/g3.115.026773
Abstract
© 2016 Tiosano et al. 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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Oxford University Press (OUP)
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G3: Genes, Genomes, Genetics
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