<italic>NOCT</italic>, a potential domestication gene impacting circadian regulation and behavioral adaptation during dog domestication

As the only carnivore domesticated by humans, the evolutionary transition of proto-domestic canids into human-associated niches remains a central unresolved question in domestication biology. Although prior work has emphasized behavioral transformations during domestication, the circadian shift from crepuscular activity in gray wolves to predominantly diurnal patterns in dogs has received comparatively little attention, despite its importance in synchronizing with human daily cycles. This study examined highly diverged loci linked to circadian system remodeling, a putative early domestication trait that likely preceded intentional human selection. Comparative genomic analyses identified NOCT as a candidate domestication gene, characterized by pronounced indel frequency divergence between gray wolves and dogs. Functional assays demonstrated that reduced NOCT expression disrupted circadian rhythmicity and was accompanied by increased myelin sheath formation in the prefrontal cortex. These neurophysiological alterations were associated with marked behavioral shifts, including extended exploratory locomotion, elevated fear and anxiety responses, and enhanced short-term memory. Collectively, these phenotypic outcomes provide empirical support for the self-domestication hypothesis and offer a mechanistic framework explaining how ancestral scavenging wolves gradually adapted to human-modified environments. Furthermore, these findings elucidate a previously underappreciated circadian-neurodevelopmental axis in canid domestication and advance understanding of the evolutionary processes that enabled the emergence of dogs as the only carnivore companion species for humans.