Human local adaptation of the TRPM8 cold receptor along a latitudinal cline
Some human populations were likely under strong pressure to adapt biologically to cold climates during their colonization of non-African territories in the last 50,000 years. Such putative adaptations required genetic variation in genes that could mediate adaptive responses to cold. TRPM8 is potentially one such gene, being the only known receptor for the sensation of moderate cold temperature. We show that a likely regulatory genetic variant nearby TRPM8 has several signatures of positive selection raising its frequency in Eurasian populations during the last 25,000 years. While the genetic variant was and is rare in Africa, it is now common outside of Africa, with frequencies that strongly correlate with latitude and are highest in northern European populations. Interestingly, this same genetic variant has previously been strongly associated with migraine. This suggests that adaptation to cold has potentially contributed to the variation in migraine prevalence that exists among human groups today.