The emergence of the vasopressin and oxytocin hormone receptor gene family lineage: Clues from the characterization of vasotocin receptors in the sea lamprey (Petromyzon marinus)

• We identified five putative vasotocin receptor genes in the jawless sea lamprey.
• Tissue expression patterns reveal homologies with jawed vertebrate orthologs.
• Phylogeny indicates three V1/oxytocin-clade receptors, a V2B and a V2C receptor.
• Each of two paralogous lamprey scaffolds contains a pair of syntenic V1–V2 genes.
• Synteny analysis supports a shared one-round whole-genome duplication scenario.

The sea lamprey (Petromyzon marinus) is a jawless vertebrate at an evolutionary nexus between invertebrates and jawed vertebrates. Lampreys are known to possess the arginine vasotocin (AVT) hormone utilized by all non-mammalian vertebrates. We postulated that the lamprey would possess AVT receptor orthologs of predecessors to the arginine vasopressin (AVP)/oxytocin (OXT) family of G protein-coupled receptors found in mammals, providing insights into the origins of the mammalian V1A, V1B, V2 and OXT receptors. Among the earliest animals to diverge from the vertebrate lineage in which these receptors are characterized is the jawed, cartilaginous elephant shark, which has genes orthologous to all four mammalian receptor types. Therefore, our work was aimed at helping resolve the critical gap concerning the outcomes of hypothesized large-scale (whole-genome) duplication events. We sequenced one partial and four full-length putative lamprey AVT receptor genes and determined their mRNA expression patterns in 15 distinct tissues. Phylogenetically, three of the full-coding genes possess structural characteristics of the V1 clade containing the V1A, V1B and OXT receptors. Another full-length coding gene and the partial sequence are part of the V2 clade and appear to be most closely related to the newly established V2B and V2C receptor subtypes. Our synteny analysis also utilizing the Japanese lamprey (Lethenteron japonicum) genome supports the recent proposal that jawless and jawed vertebrates shared one-round (1R) of WGD as the most likely scenario.