High-throughput identification of novel conotoxins from the Chinese tubular cone snail (Conus betulinus) by multi-transcriptome sequencing

Abstract

BackgroundThe venom of predatory marine cone snails mainly contains a diverse array of unique bioactive peptides commonly referred to as conopeptides or conotoxins. These peptides have proven to be valuable pharmacological probes and potential drugs because of their high specificity and affinity to important ion channels, receptors and transporters of the nervous system. Most previous studies have focused specifically on the conopeptides from piscivorous and molluscivorous cone snails, but little attention has been devoted to the dominant vermivorous species.ResultsThe vermivorous Chinese tubular cone snail, Conus betulinus, is the dominant Conus species inhabiting the South China Sea. The transcriptomes of venom ducts and venom bulbs from a variety of specimens of this species were sequenced using both next-generation sequencing and traditional Sanger sequencing technologies, resulting in the identification of a total of 215 distinct conopeptides. Among these, 183 were novel conopeptides, including nine new superfamilies. It appeared that most of the identified conopeptides were synthesized in the venom duct, while a handful of conopeptides were identified only in the venom bulb and at very low levels.ConclusionsWe identified 215 unique putative conopeptide transcripts from the combination of five transcriptomes and one EST sequencing dataset. Variation in conopeptides from different specimens of C. betulinus was observed, which suggested the presence of intraspecific variability in toxin production at the genetic level. These novel conopeptides provide a potentially fertile resource for the development of new pharmaceuticals, and a pathway for the discovery of new conotoxins.Electronic supplementary materialThe online version of this article (doi:10.1186/s13742-016-0122-9) contains supplementary material, which is available to authorized users.

Assessment of Biochemical and Histopathological Effects of Crude Venom of Cone Snail <i>Conus flavidus</i> on <i>albino</i> Mice

“…This is achieved through evolving strategies, including peptide folding and post-translational modifications, to produce powerful peptides that efficiently and rapidly a wide range of ion channels and signal transduction pathways of the envenomed prey nervous systems, causing immediate immobilization [8][9].…”

A Transcriptomic Survey of Ion Channel-Based Conotoxins in the Chinese Tubular Cone Snail (Conus betulinus)

“…Despite the relatively young age of the genus Conus , the slow-moving cone snails have developed successful strategies to subdue prey and defence against foes [ 5 , 9 ], including a highly complex cocktail of potent venom components with a great specificity towards a wide range of physiological targets [ 10 , 11 ]. The sophisticated venom apparatus consists of venom bulb, venom duct, and the hollow harpoon-like radula [ 12 , 13 ].…”

“…The major bioactive components of Conus venoms are a vast array of unique neurotoxic peptides, commonly referred to as conotoxins [ 13 ]. Each Conus species contains an average of over 100 unique conotoxin transcripts and 1000–2000 various conotoxin peptides [ 9 , 13 , 15 , 16 , 17 , 18 ]; therefore, up to 70,000 transcripts and 1,000,000 natural conotoxin peptides may exist in the world, which constitute a great potential resource for pharmacological research and development.…”

“…With multiple disulfide bonds, the disulfide-rich conotoxins are classified based on three criteria, including the signal region for defining superfamilies (capitalized letters with Arabic numerals), the cysteine pattern (number and connectivity) for defining cysteine frameworks (Roman numerals), and the receptor targets and types of interaction for defining pharmacology families (using lower-case Greek letters) [ 25 , 26 ]. Conotoxins are currently classified into a total of 27 gene superfamilies [ 13 , 23 , 27 , 28 ] and 13 temporary gene superfamilies for those identified in the early divergent species [ 28 , 29 , 30 ]. Conotoxins with a similar cysteine network usually carry a similar signal sequence.…”

“…In our previous report [ 13 ], a total of 215 distinct conotoxin transcripts were identified from the vermivorous C. betulinus , using both next-generation sequencing (RNA-seq) and traditional Sanger sequencing technologies. In the current study, based on the reported four transcriptomes from the venom duct and the venom bulb, we are interested in exploring ion channel active conotoxins since they play important roles inhibiting or activating ion channel receptors, we also investigated related ion channel proteins and receptors in the transcription datasets.…”