Exploring adaptive introgression in modern human circadian rhythm genes

Abstract

Interbreeding between modern humans and archaic hominins, including Neanderthals and Denisovans, occurred as modern humans migrated outside of Africa. Here, we report on evidence of introgression from archaic hominins within genomic regions associated with circadian rhythm and chronotype using 76 worldwide modern human populations from the Human Genome Diversity Project and 1000 Genomes Project. We calculated the extent of regions indicative of adaptive introgression across the autosomes and identified regions that are suggested to be under positive selection. We tested for evidence of a latitudinal cline within 36 core haplotypes along with presenting the likely archaic donor for each of these haplotypes. We identified 265 independent segments that overlap genes described as having a circadian rhythm component or contain variants and segments previously identified as being associated with circadian rhythm or chronotype. Within these segments we found 1,729 archaically derived variants with allele frequencies of at least 40% intersecting 303 genes and intergenic segments. Seventeen of these segments show evidence of positive selection, three of which are found within our core haplotypes. We found that many of our genes are associated with the immune system or gastrointestinal function. Additionally, variants associated with complex traits such as schizophrenia and bipolar disorder are present within our adaptively introgressed regions. Lastly, genes and markers associated with sleep and chronotype phenotypes and serotonin pathways were also found in our adaptive introgression results, potentially signalling selection on genes related to seasonal light variation as modern humans migrated into new environments after leaving Africa. Author summaryAs modern humans migrated out of Africa, they encountered archaic hominins, the Neanderthals and Denisovans, and interbred with them. Signatures of these admixture events can be found in populations across the world. The result of these admixture events has shaped modern human evolution regarding high altitude adaptation, immune function, and skin and hair colour, to name a few. However, much of this information has been gathered with a focus on Eurasian populations using the 1000 Genomes Project samples. Here, we take advantage of newly published resources from 76 worldwide modern human populations to investigate how strongly a role admixture played on modern human circadian rhythm genes. Circadian rhythms have been tied to sleep-wake regulation, immune function, and digestive health. We find evidence for adaptive introgression in over 300 genes and intergenic segments. Many of these genes, like AMIGO2, are associated with complex traits such as schizophrenia and bipolar disorder or with immune system function, like JAK1. Some of these traits have been previously described before regarding archaic admixture. Interestingly, many of these associated traits are influenced by circadian rhythm oscillations, providing a new perspective on interpreting these findings.