The figure above is from a very important new preprint, Human local adaptation of the TRPM8 cold receptor along a latitudinal cline. A marker in 09TRPM8, rs10166942, seem to be correlated with adaptation to cold.
Ambient temperature is a critical environmental factor for all living organisms. It was likely an important selective force as modern humans recently colonized temperate and cold Eurasian environments. Nevertheless, as of yet we have limited evidence of local adaptation to ambient temperature in populations from those environments. To shed light on this question, we exploit the fact that humans are a cosmopolitan species that inhabits territories under a wide range of temperatures. Focusing on cold perception, which is central to thermoregulation and survival in cold environments, we show evidence of recent local adaptation on TRPM8. This gene encodes for a cation channel that is, to date, the only temperature receptor known to mediate an endogenous response to moderate cold. The upstream variant rs10166942 shows extreme population differentiation, with frequencies that range from 5% in Nigeria to 88% in Finland (placing this SNP in the 0.02% tail of the FST empirical distribution). When all populations are jointly analysed, allele frequencies correlate with latitude and temperature beyond what can be explained by shared ancestry and population substructure. Using a Bayesian approach, we infer that the allele originated and evolved neutrally in Africa, while positive selection raised its frequency to different degrees in Eurasian populations, resulting in allele frequencies that follow a latitudinal cline. We infer strong positive selection, in agreement with ancient DNA showing high frequency of the allele in Europe 3,000 to 8,000 years ago. rs10166942 is important phenotypically because its ancestral allele is protective of migraine. This debilitating disorder varies in prevalence across human populations, with highest prevalence in individuals of European descent, precisely the population with the highest frequency of rs10166942 derived allele. We thus hypothesize that local adaptation on previously neutral standing variation may have contributed to the genetic differences that exist in the prevalence of migraine among human populations today.
The mechanism and adaptive story make sense. They used several methods which corrected/accounted for population structure, and noted that the allele frequency difference was still significantly predicted by variation in latitude (though not temperature).
In the plot above you can see that South Asian populations share allele frequency distributions closer to East Asians, though genetically they are somewhat closer to Europeans. Looking at the haplotype structure this variant looks to be old variation that has been under selection in Eurasia. Additionally if you look at the frequencies it doesn’t look like the sweeps are completing. Since migraines are one correlated side effect that probably makes sense.
The problem I have with this preprint is a simple one. The SNP seems to be in the HGDP browser (it’s in your 23andMe genotype if you have one, I checked). The geographic distribution doesn’t look as clear as it does in the 1000 Genomes data. In particular in the New World populations the latitudinal cline is reversed from what we’d expect.
These sorts of objections are pretty typical. And they authors did do a sophisticated statistical analysis…but sometimes visual inspection of the raw frequencies is still important when the effect is subtle. Over the next decade there is going to be a lot of sophisticated analysis of adaptation, because the low hanging fruit has been picked. But we need to still look over the results with care….