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.

Owls and larks do not exist: COVID-19 quarantine sleep habits

“…Genetics, age, gender, and environmental stimuli influence the expression of chronotype [ 7 , 9 , 10 , 12 , 17 ]. Specifically for genetics, researchers indicate from ten to 36 genes that may be involved in human chronobiology [ 24 , 25 ]. How all these variables interact to produce seven different human chronotypes is difficult to say.…”

“…In 2018, Putilov et al. investigated 1665 polymorphisms in 36 chronobiology-related genes and found out that such evolutionary changes are actually took place as a part of general adaptation [ 34 ]. We doubt that various peculiarities of human sleep habits should be called disorders.…”

Light at night and risk of breast cancer: a systematic review and dose–response meta-analysis

“…An explanation may be the presence of different alleles of their circadian genes, which acted to adapt the organism to different living conditions such as different latitudes. [ 80 ]. Finally, we may hypothesize that if people residing in “darkest countries” have artificial light kept on also during the daytime, they may not be as strongly influenced by higher levels of LAN because of different environment-adaptive alleles which acted to adapt the organism to light regimes diverse from the natural ones, as has been shown in animals [ 81 ].…”

Archaic Introgression Shaped Human Circadian Traits

“…Previous studies in humans found a correlation between latitude and chronotype (morningness vs. eveningness) variation ( Leocadio-Miguel et al 2017 ; Randler and Rahafar 2017 ; Lowden et al 2018 ) and a latitudinal cline in some circadian allele frequencies ( Dorokhov et al 2018 ; Putilov et al 2018 , 2019 ), highlighting the contribution of the environment to behavior and circadian biology. Many human health effects are linked to the misalignment of chronotype ( Knutson and von Schantz 2018 ), including cancer, obesity ( Gyarmati et al 2016 ; Papantoniou et al 2016 , 2017 ; Gan et al 2018 ; Shi et al 2020 ; Yousef et al 2020 ), and diabetes ( Gan et al 2015 ; Larcher et al 2015 , 2016 ).…”