Abstract
The piscivorous cone snail Conus tulipa has evolved a net-hunting strategy, akin to the deadly Conus geographus, and is considered the second most dangerous cone snail to humans. Here, we present the first venomics study of C. tulipa venom using integrated transcriptomic and proteomic approaches. Parallel transcriptomic analysis of two C. tulipa specimens revealed striking differences in conopeptide expression levels (2.5-fold) between individuals, identifying 522 and 328 conotoxin precursors from 18 known gene superfamilies. Despite broad overlap at the superfamily level, only 86 precursors (11%) were common to both specimens. Conantokins (NMDA antagonists) from the superfamily B1 dominated the transcriptome and proteome of C. tulipa venom, along with superfamilies B2, A, O1, O3, con-ikot-ikot and conopressins, plus novel putative conotoxins precursors T1.3, T6.2, T6.3, T6.4 and T8.1. Thus, C. tulipa venom comprised both paralytic (putative ion channel modulating α-, ω-, μ-, δ-) and non-paralytic (conantokins, con-ikot-ikots, conopressins) conotoxins. This venomic study confirms the potential for non-paralytic conotoxins to contribute to the net-hunting strategy of C. tulipa.
Highlights
Venomous animals have long been regarded as a valuable source of bioactive peptides that can have therapeutic potential, with several currently used clinically [1,2,3,4]
The Specimen 1 (S1) intact venom duct yielded 522 conotoxin precursors that clustered into 16 known gene superfamilies (Table S1), while stripped venom duct of Specimen 2 (S2) yielded fewer (328) conotoxin precursors that clustered into 18 known gene superfamilies (Table 1 and Table S1)
16 gene superfamilies were common to both specimens (Table 1, Figure 1), with superfamily B1 encoding conantokins dominating the venom gland transcriptome of both specimens
Summary
Venomous animals have long been regarded as a valuable source of bioactive peptides that can have therapeutic potential, with several currently used clinically [1,2,3,4]. Marine cone snails produce relatively short cysteine-rich bioactive peptides called conotoxins that target various ion channels and receptors [5]. More than 800 species of snails in the genus Conus have been documented [7] with most species producing in excess of 1000 conotoxins [8]. As these molluscs are sluggish and small, it is clear that their complex venom arsenal has contributed to their success as predators [9,10]. Venomics has contributed to recent breakthrough in our understanding of the ecology and evolution of cone snails, including the role of defence in diet diversification [12] and biological messiness [13,14,15,16] in the accelerated diversification of conopeptides
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