Transcriptional instability prevents dispersion of functional vomeronasal receptor genes [mouse]

Rodents perceive pheromones via vomeronasal receptors encoded by the Vr and Fpr gene superfamilies. The evolution of these latter is exceptionally dynamic. We report here that high numbers of V1r pseudogenes are scattered in mammalian genomes, contrasting with the clustered organization of functional V1r and Fpr genes. We also found that V1r pseudogenes are more likely to be expressed when located in a functional V1r gene cluster than when isolated. To explore the potential regulatory role played by the association of functional vomeronasal receptor genes with their clusters, we dissociated the mouse Fpr-rs3 from its native cluster via transgenesis. Singular and specific transgenic Fpr-rs3 transcription was observed in young vomeronasal neurons, but was only transient. Our data point to the existence of transcription stabilizing elements not coupled to vomeronasal gene units but rather associated with vomeronasal gene clusters, and thus explain the evolutionary conserved clustered organization of functional vomeronasal genes. Overall design: Vomeronasal receptor gene expression profiling in the mouse vomeronasal organ using whole tissue and single-cell RNA sequencing.