Clustering of vomeronasal receptor genes is required for transcriptional stability but not for choice.

Rodents perceive pheromones via vomeronasal receptors encoded by highly evolutionarily dynamic Vr and Fpr gene superfamilies. 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 study of natural and artificial dispersed gene duplications uncovers the existence of transcription-stabilizing elements not coupled to vomeronasal gene units but rather associated with vomeronasal gene clusters and thus explains the evolutionary conserved clustered organization of functional vomeronasal genes.

Reorganisation of Hoxd regulatory landscapes during the evolution of a snake-like body plan.

Within land vertebrate species, snakes display extreme variations in their body plan, characterized by the absence of limbs and an elongated morphology. Such a particular interpretation of the basic vertebrate body architecture has often been associated with changes in the function or regulation of Hox genes. Here, we use an interspecies comparative approach to investigate different regulatory aspects at the snake HoxD locus. We report that, unlike in other vertebrates, snake mesoderm-specific enhancers are mostly located within the HoxD cluster itself rather than outside. In addition, despite both the absence of limbs and an altered Hoxd gene regulation in external genitalia, the limb-associated bimodal HoxD chromatin structure is maintained at the snake locus. Finally, we show that snake and mouse orthologous enhancer sequences can display distinct expression specificities. These results show that vertebrate morphological evolution likely involved extensive reorganisation at Hox loci, yet within a generally conserved regulatory framework.