When brought into captivity, wild animals can adapt to domestication within 10 generations. Such adaptations may decrease fitness in natural conditions. Many selective pressures are disrupted in captivity, including social behavioral networks. Although lack of sociality in captivity appears to mediate domestication, the underlying mechanisms are not well understood. Additionally, determining the contribution of genetic inheritance vs. transgenerational effects during relaxed selection may provide insight into the flexibility of adaptation. When wild-derived mice kept under laboratory conditions for eight generations were reintroduced to sociality and promiscuity (free mate choice), they adapted within two generations. Fitness assessments between this promiscuous lineage and a monogamous laboratory lineage revealed malespecific effects. Promiscuous-line males had deficits in viability, but a striking advantage in attracting mates, and their scent marks were also more attractive to females. Here, we investigate mechanistic details underlying this olfactory signal and identify a role of major urinary protein (MUP) pheromones. Promiscuous-line males inherit higher MUP expression than monogamous-line males through transgenerational inheritance. Sociality-driven maternal and paternal effects reveal intriguing conflicts among parents and offspring over pheromone expression. MUP up-regulation is not driven by hormone-driven transduction pathways, but rather is associated with reduction in DNA methylation of a CpG dinucleotide in the promoter. This reduction in methylation could enhance transcription by promoting the binding of transcription factor USF1 (upstream stimulatory factor 1). Finally, we experimentally demonstrate that increased MUP expression is a female attractant. These results identify molecular mechanisms guiding domestication and adaptive responses to fluctuating sociality.social selection | sexy sons | epigenetics W ild animals bred in captivity have been observed to adapt to domestication within 10 generations (1-4). As a result, captive bred animals often have reduced fitness when reintroduced to natural conditions (5). Selective pressures disrupted by captivity include inbreeding avoidance, effective population size, disease exposure, predation, and sexual selection. For the latter example, evidence suggests that lack of social context for mate choice mediates adaptation to captivity (6). This context is especially relevant for social animals because the opportunity for mating success is regulated by hierarchical behavioral networks (i.e., social selection) (7), and this information is missing in captivity. The molecular mechanisms underlying phenotypes affected by lack of social selection are poorly understood. Furthermore, rapid adaptation to captivity raises questions about the roles of genetic inheritance vs. transgenerational effects (i.e., inheritance independent of genetic variation) (8). Resolving the mechanistic and hereditary basis of these transitions can provide insight into the flexibilit...
