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

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 rat vomeronasal organ using whole tissue and single-cell RNA sequencing.

啮齿动物通过由Vr基因超家族与Fpr基因超家族编码的犁鼻器受体（vomeronasal receptor）感知信息素，该类基因家族的演化过程极具动态性。我们在此报道，大量的V1r假基因分散分布于哺乳动物基因组中，这与功能性V1r基因和Fpr基因的成簇组织形式形成鲜明对比。我们还发现，相较于孤立存在的V1r假基因，位于功能性V1r基因簇中的假基因更易被表达。为探究功能性犁鼻器受体基因与其基因簇的关联所发挥的潜在调控作用，我们通过转基因技术将小鼠Fpr-rs3基因从其原生基因簇中分离出来。在年轻的犁鼻神经元中可观察到单一且具有特异性的转基因Fpr-rs3转录，但该转录仅为瞬时性的。我们的数据表明存在一类转录稳定元件，其并不与犁鼻器基因单元偶联，而是与犁鼻器基因簇相关联，这也解释了功能性犁鼻器基因在进化中保守的成簇组织形式。实验整体设计：通过全组织RNA测序与单细胞RNA测序（single-cell RNA sequencing）技术，对大鼠犁鼻器中的犁鼻器受体基因开展表达谱分析。