The evolution of oxytocin receptor signaling

Oxytocin is a neuromodulator and hormone that helps coordinate a variety of physiological and behavioral functions. Oxytocin exerts its diverse effects by binding to oxytocin receptors throughout the brain and the periphery, which initiates various signaling cascades. The location and distribution of oxytocin receptors can differ between species, which can facilitate species-specific behaviors that promote survival and reproduction. Yet, despite the increasing interest in the oxytocin signaling system, the extent of its functions in human health and wellbeing are currently not well understood. Pinpointing the evolutionary trajectory of the oxytocin receptor is one approach that can help unravel the current purpose of the oxytocin signaling system. Here, we demonstrate three analytical approaches that help uncover the evolutionary history of the oxytocin receptor: Sequence homology searches, synteny mapping, and positive selection analysis. Our non-technical guide includes suggestions for software packages and previously published analysis scripts that can be used for pre-processing and performing the analysis. These complementary analytical approaches have helped uncover the evolutionary history of the oxytocin receptor, suggesting that oxytocin receptor orthologs can be traced back to the origin of vertebrates and that the oxytocin receptor has been positively selected in an ancient marsupial branch.