Adaptive introgression in modern human circadian rhythm genes

Christopher Kendall; Amin Nooranikhojasteh; Guilherme Debortoli; Vinicius Cauê Furlan Roberto; Marla Mendes; David Samson; Esteban Parra; Bence Viola; Michael A Schillaci

doi:10.1038/s44323-025-00060-2

Adaptive introgression in modern human circadian rhythm genes

NPJ Biol Timing Sleep. 2025;2(1):41. doi: 10.1038/s44323-025-00060-2. Epub 2025 Dec 4.

Authors

Christopher Kendall^{1

2}, Amin Nooranikhojasteh³, Guilherme Debortoli⁴, Vinicius Cauê Furlan Roberto^{5

6}, Marla Mendes^{5

6}, David Samson^{4

7}, Esteban Parra⁴, Bence Viola², Michael A Schillaci⁸

Affiliations

¹ Neurosciences and Mental Health Department, The Hospital for Sick Children, Toronto, ON Canada.
² Department of Anthropology, University of Toronto, Toronto, ON Canada.
³ Epigenome Lab, Princess Margaret Cancer Centre, University Health Network, Toronto, ON Canada.
⁴ Department of Anthropology, University of Toronto Mississauga, Mississauga, ON Canada.
⁵ The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON Canada.
⁶ Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON Canada.
⁷ Sleep and Human Evolution Lab, University of Toronto Mississauga, Mississauga, ON Canada.
⁸ Department of Anthropology, University of Toronto Scarborough, Scarborough, ON Canada.

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 adaptive introgression from archaic hominins within genomic regions associated with circadian rhythm cycling, chronotype, and sleep using 76 worldwide modern human populations from the Human Genome Diversity Project and 1000 Genomes Project. We identified 265 independent segments suggestive of adaptive introgression, where 22 of these segments show evidence of positive selection. We tested for evidence of a latitudinal cline within 35 core haplotypes, finding no clear latitude gradient, and identified the likely archaic donor for each of these haplotypes. We found that several genes with evidence of adaptive introgression are associated with affective disorders, chronotype, and respiratory diseases. Lastly, many of the variants are eQTLs for several genes that are significantly enriched in immunity pathways.

Keywords: Bipolar disorder; Circadian mechanisms; Circadian regulation; Circadian rhythms; Psychiatric disorders.