Molecular biology of the oxytocin receptor: a comparative approach.

Introduction The nonapeptides oxytocin and vasopressin belong to an ancient peptide hormone family with representatives in both protastome and deuterostome lineages. The two mammalian hormones themselves probably diverged from a common ancestor at about the time that vertebrates evolved on the earth. There are discrete oxytocin-like and vasopressin-like peptides in teleost fish; only in cyclostomes does it appear that there is only one member of this family [l]. Correspondingly, the receptors for these hormones must also have retained structural and functional features reflecting the balance between conservative and divergent evolution. We and others have cloned genes from several different species, which encode receptor proteins for members of the oxytocin-like nonapeptide hormones. Although representing a broad range of species, the physiologies in which these receptors are involved are very similar, and to date all species analysed appear to have a single homologous oxytocin receptor gene, the encoded receptor protein of which is linked to the inositol trisphosphate-protein kinase C signal-transduction pathway. We have taken advantage of this situation to apply a comparative molecular approach to analyse those structural features of the oxytocin receptor and its gene that are subject to high conservative selective pressure and hence belie an important role essential for the functional or structural integrity of the receptor. Amino acid and nucleotide (mRNA) sequence information is available for several eutherian species, e.g. human [2], rat [3], pig [4], bovine [5], sheep [6], mouse [7], vole [8] and marmoset monkey [9]. In addition, genomic sequence is available for human [lo], rat [3], bovine [5], mouse [7] and vole [8]. Recently, we have begun studying the equivalent receptor in a marsupial, the tammar wallaby [ 111 , and preliminary cDNA and protein sequence is available for