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Background  Vitamin D is essential for a wide range of physiological processes including immune function and calcium homeostasis. Recent investigations have identified candidate genes which are strongly linked to concentrations of 25-hydroxyvitamin D. Since there is insufficient UVB radiation to induce year-round cutaneous synthesis of vitamin D at latitudes distant from the equator it is likely that these genes were subject to forces of natural selection. We used the fixation index (F ST ) to measure differences in allele frequencies in 993 individuals from ten populations to identify the presence of evolutionary selection in genes in the vitamin D pathway. We then explored the length of haplotypes in chromosomes to confirm recent positive selection.    Results  We find evidence of positive selection for  DHCR7,  which governs availability of 7-dehydrocholesterol for conversion to vitamin D 3  by the action of sunlight on the skin. We show that extended haplotypes related to vitamin D status are highly prevalent at Northern latitudes (Europe 0.72, Northeast Asia 0.41). The common  DHCR7  haplotype underwent a recent selective sweep in Northeast Asia, with relative extended haplotype homozygosity of 5.03 (99th percentile). In contrast,  CYP2R1 , which 25-hydroxylates vitamin D, is under balancing selection and we found no evidence of recent selection pressure on  GC , which is responsible for vitamin D transport.    Conclusions  Our results suggest that genetic variation in  DHCR7  is the major adaptation affecting vitamin D metabolism in recent evolutionary history which helped early humans to avoid severe vitamin D deficiency and enabled them to inhabit areas further from the equator.

DHCR7 mutations linked to higher vitamin D status allowed early human migration to Northern latitudes