The cone snails are a biodiverse lineage of ca 700 species of venomous marine gastropods. Several species have been intensively studied; each cone snail venom expresses 50-150 venom components, mostly small, disulfide-rich peptides. It is clear that the venom is organized into groups of bioactive peptides that act together; these groups have been called “cabals”. The cone snails use a combination drug strategy to achieve each specific physiological endpoint. Most remarkably, the genes that encode these venom peptides are subject to an unprecedented rate of accelerated evolution, so that venom peptides are different in each species.
Recently, a particularly insightful example of venom evolution was gained by the discovery that cone snails use insulin to make their prey hypoglycemic (and therefore easier to capture). Early in the evolution of the genus, there was a duplication of the insulin gene; the endogenous copy has remained essentially conserved; in contrast, the copy expressed in venom has greatly diversified. A comparison between the endogenous gene, and the insulin “exogene” is instructive in reflecting the different selective pressures that each of the duplicated copies has been subject to over evolutionary time. An overview of these differences will be presented.