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 vertebrates 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 convergent evolution from different types of gene. To investigate this issue, we cloned the gene encoding the molluscan insulin-related peptide III (MIP III) from the freshwater snail, Lymnaea stagnalis. The predicted MIP III preprohormone had the overall organization of preproinsulin, with a signal peptide and A and B chains, connected by two putative C peptides. Although MIP III was found to share key features with vertebrate insulins, it also had unique structural characteristics in common with the previously identified MIPs I and II, thus forming a distinct 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 exons and two introns, of which the second intron interrupts the coding region of the C peptides. Our data therefore demonstrate that in the Archaemetazoa, 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.