NG peptides: a novel family of neurophysin-associated neuropeptides.

Neurophysins are prohormone-derived polypeptides that are required for biosynthesis of the neurohypophyseal hormones vasopressin and oxytocin. Accordingly, mutations in the neurophysin domain of the human vasopressin gene can cause diabetes insipidus. The association of neurophysins with vasopressin/oxytocin-type peptides dates back to the common ancestor of bilaterian animals and until recently it was thought to be unique. This textbook perspective on neurophysins changed with the discovery of a gene in the sea urchin Strongylocentrotus purpuratus (phylum Echinodermata) encoding a precursor protein comprising a neurophysin domain in association with NGFFFamide, a myoactive neuropeptide that is structurally unrelated to vasopressin/oxytocin-type neuropeptides (Elphick, M.R., Rowe, M.L., 2009. NGFFFamide and echinotocin: structurally unrelated myoactive neuropeptides derived from neurophysin-containing precursors in sea urchins. J. Exp. Biol. 212, 1067-1077). What is not known, however, is when and how the association of neurophysin with NGFFFamide-like neuropeptides originated. Here I report the discovery of genes encoding proteins comprising a neurophysin domain in association with putative NGFFFamide-like peptides in the hemichordate Saccoglossus kowalevskii (NGFWNamide and NGFYNamide) and in the cephalochordate Branchiostoma floridae (SFRNGVamide). Together with NGFFFamide, these peptides constitute a novel family of neuropeptides in invertebrate deuterostomes that are derived from neurophysin-containing precursors and that have the sequence motif NG - "NG peptides". Genes encoding NG peptides in association with neurophysin were not found in protostomes, urochordates or vertebrates. Interestingly, however, SFRNGVamide is identical to the N-terminal region of neuropeptide S, a peptide that modulates arousal and anxiety in mammals, whilst NGFFFamide shares sequence similarity with SIFamide (AYRKPPFNGSIFamide), a neuropeptide that regulates sexual behaviour in Drosophila. Collectively, these data indicate that in an ancestor of extant deuterostomes a remarkable and unique event in the evolution of neuropeptide signalling systems occurred when a neurophysin-encoding exon(s) derived from a vasopressin/oxytocin-type neuropeptide gene became transcriptionally linked with another family of neuropeptides - NG peptides.