Animal venoms are a rich source of pharmacological compounds with ecological and evolutionary significance, as well as with therapeutic and biotechnological potentials. Among the most promising venomous animals, cone snails produce potent neurotoxic venom to facilitate prey capture and defend against aggressors. Conus striatus, one of the largest piscivorous species, is widely distributed, from east African coasts to remote Polynesian Islands. In this study, we investigated potential intraspecific differences in venom composition between distinct geographical populations from Mayotte Island (Indian Ocean) and Australia (Pacific Ocean). Significant variations were noted among the most abundant components, namely the κA-conotoxins, which contain three disulfide bridges and complex glycosylations. The amino acid sequence of a novel κA-conotoxin SIVC, including its N-terminal acetylated variant, was deciphered using tandem mass spectrometry (MS/MS). In addition, the glycosylation pattern was found to be consisting of two HexNAc and four Hex for the Mayotte population, which diverge from the previously characterized two HexNAc and three Hex combinations for this species, collected elsewhere. Whereas the biological and ecological roles of these modifications remain to be investigated, population-specific glycosylation patterns provide, for the first time, a new level of intraspecific variations in cone snail venoms.

Cone snails are carnivorous marine predators that prey on mollusks, worms, or fish. They purposefully inject a highly diversified and peptide-rich venom, which can vary according to the predatory or defensive intended use. Previous studies have shown some correlations between the predation- and defense-evoked venoms and specific sections of the venom gland. In this study, we focus on the characterization of the venom of Cylinder canonicus, a molluscivorous species collected from Mayotte Island. Integrated proteomics and transcriptomics studies allowed for the identification of 108 conotoxin sequences from 24 gene superfamilies, with the most represented sequences belonging to the O1, O2, M, and conkunitzin superfamilies. A comparison of the predatory injected venom and the distal, central, and proximal sections of the venom duct suggests mostly distal origin. Identified conotoxins will contribute to a better understanding of venom–ecology relationships in cone snails and provide a novel resource for potential drug discovery.