Distinct evolutionary trajectories of V1R clades across mouse species

Abstract

29Background: Many animals rely heavily on olfaction to navigate their environment. Among rodents, 30 olfaction is crucial for a wide range of social behaviors. The vomeronasal olfactory system in particular 31 plays an important role in mediating social communication, including the detection of pheromones and 32 recognition signals. Currently, very few vomeronasal receptors have known ligands, which severely limits 33 our understanding of chemosensory-driven social communication. In this study we examine patterns of 34 vomeronasal type-1 receptor (V1R) evolution in the house mouse and related species within the genus 35 Mus. By exploring the evolution of these receptors, we provide insight into the functional roles of receptor 36 subtypes as well as the dynamics of gene family evolution. 37Results: We generated transcriptomes from the vomeronasal organs of 5 Mus species, and produced 38 high quality V1R repertoires for each species. We find that V1R clades in the house mouse and relatives 39 exhibit distinct evolutionary trajectories. Some clades are highly conserved, while others reveal patterns 40 of rapid evolutionary change. We identify putative species-specific gene expansions, including a dramatic 41 clade D expansion in the house mouse. While gene gains are abundant, we detect very few gene losses. 42We describe a novel V1R clade and highlight candidate receptors for future de-orphanization. Based on 43 clade-level evolutionary patterns, we identify receptor families that are strong candidates for detecting 44 social signals and predator cues. Our results further support the view that V1Rs are important for 45 detecting the physiological status of conspecifics, particularly female estrus cues. 46Conclusion: Analysis of clade-level evolution is critical for understanding species' chemosensory 47 adaptations. This study provides clear evidence that V1R clades are characterized by distinct 48 evolutionary trajectories. As receptor evolution is shaped by ligand identity, these results provide a