How have our clocks evolved? Adaptive and demographic history of the out-of-African dispersal told by polymorphic loci in circadian genes

ABSTRACT

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.

KEYWORDS:

• Latitudinal cline
• clock genes
• SNP
• 1000 Genomes Project
• morning-evening preference
• polygenic selection
• skin pigmentation
• migration out of Africa

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

The studies of AAP were supported by grants from the Russian Foundation for Basic Research (grant numbers 07-06-00263-а, 10-06-00114-а, 13-06-00042-a and 16-06-00235-a) and the Russian Foundation for Humanities (grant numbers 06-06-00375-a, 12-06-18001-e and 15-06-10403-a). The studies of VBD were supported by grants from the Russian Foundation for Humanities (grant numbers 15-06-10909a, 15-06-10874а, and 14-06-00963a).