Venomic Interrogation Reveals the Complexity of Conus striolatus Venom

Given the complexity of cone snail venoms, high throughput venomics approaches are required to fully investigate venom composition, envenomation strategies, and evolutionary trajectories. This study describes 158 conotoxins in the venom transcriptome of the little studied C. striolatus from the fish hunting clade Pionoconus. Despite similar gene superfamily distributions along the venom duct, only 18 common transcripts were identified between distal, central, and proximal venom duct transcriptomes. Proteomic analysis of the injected predatory venom collected from the same individual revealed an ~18-fold enhanced complexity at the proteomic level, consistent with complex post-translational modifications and variable venom peptide processing occurring in the venom duct. Overall, C. striolatus venom was dominated by M, O1, O2, and A gene superfamily conotoxins and conkunitzins, which are potential modulators of sodium, calcium, and potassium channels. Conkunitzins and gene superfamily A peptides dominated the proximal over the distal duct, the M and O1 gene superfamily peptides were distributed along the full length of the duct, while the O2 gene superfamily peptides dominated the distal duct. Interestingly, the predatory injected venom of C. striolatus was dominated by peptides from gene superfamilies M, O1, O2, A, and conkunitzins, suggesting the predatory venom of C. striolatus may arise at multiple sites along the venom duct.