Abstract
The vertebrate oxytocin and vasopressin receptors form a family of G-protein-coupled receptors (GPCRs) that mediate a large variety of functions, including social behavior and the regulation of blood pressure, water balance and reproduction. In mammals four family members have been identified, three of which respond to vasopressin (VP) named V1A, V1B and V2, and one of which is activated by oxytocin (OT), called the OT receptor. Four receptors have been identified in chicken as well, but these have received different names. Until recently only V1-type receptors have been described in several species of teleost fishes. We have identified family members in several gnathostome genomes and performed phylogenetic analyses to classify OT/VP-receptors across species and determine orthology relationships. Our phylogenetic tree identifies five distinct ancestral gnathostome receptor subtypes in the OT/VP receptor family: V1A, V1B, V2A, V2B and OT receptors. The existence of distinct V2A and V2B receptors has not been previously recognized. We have found these two subtypes in all examined teleost genomes as well as in available frog and lizard genomes and conclude that the V2A-type is orthologous to mammalian V2 receptors whereas the V2B-type is orthologous to avian V2 receptors. Some teleost fishes have acquired additional and more recent gene duplicates with up to eight receptor family members. Thus, this analysis reveals an unprecedented complexity in the gnathostome repertoire of OT/VP receptors, opening interesting research avenues regarding functions such as regulation of water balance, reproduction and behavior, particularly in reptiles, amphibians, teleost fishes and cartilaginous fishes.
Highlights
The classical neuroendocrine nonapeptides vasopressin and oxytocin, released from hypothalamic neurons that extend their axons into the posterior pituitary, have profound effects on salt and water balance and reproduction, respectively [6, 9, 32]
The vertebrate oxytocin and vasopressin receptors form a family of G-protein-coupled receptors (GPCRs) that mediate a large variety of functions, including social behavior and the regulation of blood pressure, water balance and reproduction
In mammals four family members have been identified, three of which respond to vasopressin (VP) named V1A, V1B and V2, and one of which is activated by oxytocin (OT), called the OT receptor
Summary
The classical neuroendocrine nonapeptides vasopressin and oxytocin, released from hypothalamic neurons that extend their axons into the posterior pituitary, have profound effects on salt and water balance and reproduction, respectively [6, 9, 32] Their widespread distribution in the brain in mammals correlates with important roles as neuropeptides influencing social behavior [11, 20] including social olfactory memory in mice [12] and trust and generosity in humans [28, 53]. Oxytocin and vasopressin arose from a common ancestral gene by a local duplication in a gnathostome ancestor, and the separate oxytocin and vasopressin lineages arose in early vertebrate evolution [16, 17] This makes other names for these peptides in the gnathostomes redundant in an evolutionary perspective, and establishes a likely evolutionary time frame for the divergence of oxytocin and vasopressin systems, including the corresponding receptors
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