Climate and land use change have increased human–wildlife interactions, potentially reducing wild species density and prompting behavioral adaptations to urbanized environments. It is still debated if behavioral responses are mainly the result of phenotypic plasticity or if they were driven by anthropic selective pressures, especially in small populations where genetic drift is strong. Our study focused on the small Apennine brown bear population (Ursus arctos marsicanus), which has coexisted with humans in Central Italy for millennia. We characterized genomic diversity and identified adaptation signals distinctive to this population by comparing newly generated and published whole-genome resequencing data from Apennine, Central European, and North American brown bears. Apennine brown bears exhibited reduced genomic diversity, higher inbreeding, and larger realized genetic load compared to other brown bears. We showed that Apennine brown bears possess a unique genomic diversity pattern including selective signatures at genes associated with reduced aggressiveness (eg DCC, SLC13A5). Within these genes, most of the newly discovered variants were located in noncoding regions and some of them were predicted to alter splicing factor binding sites, highlighting the contribution of noncoding variation in shaping complex phenotypes. Our results support the hypothesis that human-induced selection has promoted behavioral changes even in small- and long-isolated populations, reducing conflicts and contributing to the long-term persistence of a large mammal species and its coexistence with humans.
