NOCT, a potential domestication gene impacting circadian rhythm and behaviors during dog domestication

As the only domesticated carnivore, how proto-domestic canids first adapted to human society at the onset of domestication remains a central enigma in the history of animal domestication. While previous studies have extensively characterized the behavioral transformation during domestication, the circadian shift from the crepuscular rhythms in grey wolves to diurnal patterns in dogs has received limited attention, despite its critical role in adapting to human activity cycles. Here we investigated the highly diverged genes associated with circadian system reorganization, a potential domestication trait preceding the conscious human selection. Our findings identified NOCT as a candidate domestication gene with distinct indel frequency shifts from grey wolves to dogs. Functional analyses revealed that reduced NOCT induced circadian rhythm disruption, accompanied with enhanced myelin sheath formation in the prefrontal cortex. These physiological alterations led to profound behavioral changes, including prolonged exploratory locomotion, heightened fear/anxiety response, and improved short-term memory. Collectively, these behavioral changes provide empirical support for the self-domestication hypothesis, suggesting how ancient scavenging wolves may have gradually adapted to human environments. Our study provides new insights into the evolutionary mechanisms driving the successful domestication of the sole carnivore companion species.