Cone snails are predatory marine gastropods with one of the most hyper-diversified venomous systems with 850 species classified into three groups based on the prey preference (fish, mollusc, and worm). Fish hunters and mollusc hunters have independently emerged from ancestral worm hunters. The chemical warfare used across species and lineages have evolved through repurposing and optimising of ancestral venom components to acquire new functions and via recruiting new toxins, explaining the remarkable diversity of cone snail venoms.
In this study, efforts were taken to understand the biochemical innovations used by the fish hunters of the Pionoconus clade for envenomation. Among 8 known fish hunting cone snail clades, the Pionoconus clade of fish hunters are by far the most successful with >40 species. Five species from the Pionoconus clade were used to understand the molecular mechanisms of their envenomation strategy and special distribution of major peptide classes across the venom duct. Further efforts were taken to compare and contrast their venom composition against two other lineages of fish hunters (Gastridium and Chelyconus) and ancestral worm hunting species, to better understand the diversification of toxins across these diverse clades.
Interestingly, the fundamental structure of inhibitory peptides of A (alpha-conotoxins), O1 (omega and delta conotoxins) and M (mu conotoxins) are conserved across all lineages of cone snails with fish hunting linages having higher sequence similarity compared to worm hunting toxins. Each clade of fish hunters employ an unique chemical warfare for envenomation.
The Pionoconus clade of fish hunters exclusively express excitatory κA-conotoxins as the major componets in both predatory and defensive venoms and could be suggested as the key evolutionary drivers of the successful radiation of this clade. We propose that κA-conotoxins have evolved through adaptive evolution via repurposing of ancestral inhibitory aA conotoxins to facilitate the dietary shift to fish hunting.