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

BMC Evolutionary Biology

Robert Walton¹  Elina Hyppönen²  Chris J Griffiths¹  Adrian R Martineau¹  Valerie Kuan¹ 

[1] Queen Mary University of London, Barts and The London School of Medicine and Dentistry, Blizard Institute, 58 Turner Street, London E1 2AB, UK;School of Population Health, University of South Australia, Adelaide, Australia

关键词: Long range haplotype test;    Fixation index;    DHCR7;    Vitamin D;    Evolutionary selection;   

Others  :  1086869
DOI  :  10.1186/1471-2148-13-144

 received in 2013-05-28, accepted in 2013-07-04,  发布年份 2013

【 摘 要 】

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 D₃ 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.

【 授权许可】

   
2013 Kuan et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 2.

Figure 3.

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