Аннтотация

© 2018 Taylor  &  Francis Group, LLC. The mechanism of the molecular circadian clocks is currently understood as a transcription/translation feedback loop involving more than ten genes. Genetic variation at some of loci in these genes has been shaped by adaptation to environmental factors. In particular, latitudinal clines in allele frequency were documented in several animal species, but the contradictory conclusions were drawn from the results of rare human studies. Here we tested whether the out-of-African dispersal of human populations to higher latitudes of the Eurasian continent was associated with latitude-dependent shifts in allele frequency at polymorphic loci in genes of three (reference, circadian and skin pigmentation) groups. In order to detect the genetics-based signatures left by latitude-driven adaptation and to distinguish them from the confounding effects of population demographic history, we analyzed allele frequencies in 1594 individuals from 5 African and 11 Eurasian populations of the 1000 Genomes Project Phase 3. Up to 80 polymorphisms with global minor allele frequency > 0.2 were sampled from each of 36 genes (1665 polymorphisms in total). As expected, percentage of polymorphisms demonstrating both significantly enlarged differentiation of Eurasian populations on allele frequency and significant correlation between latitude and allele frequency was significantly higher in pigmentation genes compared to circadian genes and in circadian genes compared to reference genes. We also showed that the latitude-driven adaptation can be separated from genetic consequences of demographic perturbations by comparison of results obtained for the whole set of 16 African and Eurasian populations with results for only Eurasian populations that share the common demographic history. The revealed latitudinal clines in allele frequency seemed to be shaped by polygenic selection occurring by small allele frequency shifts spread across many loci in circadian and non-circadian genes. The present results provided a rationale for necessity to facilitate candidate gene studies by prioritizing genetic markers of chronotype.