EVOLUTIONARY CONSERVATION OF THE INSULIN GENE STRUCTURE IN INVERTEBRATES - CLONING OF THE GENE ENCODING MOLLUSCAN INSULIN-RELATED PEPTIDE-III FROM LYMNAEA-STAGNALIS

Although insulins and structurally related peptides are found in verte brates as well as in invertebrates, it is not clear whether the genes encoding these hormones have emerged from a single ancestral (insulin) -type of gene or, alternatively, have arisen independently through con vergent evolution from different types of gene. To investigate this is sue, we cloned the gene encoding the molluscan insulin-related peptide III (MIP III) from the freshwater snail, Lymnaea stagnalis. The predi cted MIP III preprohormone had the overall organization of preproinsul in, with a signal peptide and A and B chains, connected by two putativ e C peptides. Although MIP III was found to share key features with ve rtebrate insulins, it also had unique structural characteristics in co mmon with the previously identified MIPs I and II, thus forming a dist inct class of MIP peptides within the insulin superfamily. MIP III is synthesized in neurones in the brain. It is encoded by a gene with the overall organization of the vertebrate insulin genes, with three exon s and two introns, of which the second intron interrupts the coding re gion of the C peptides. Our data therefore demonstrate that in the Arc haemetazoa, the common ancestor of the vertebrates and invertebrates, a primordial peptide with a two-chain insulin configuration encoded by a primordial insulin-type gene must have been present.