High Throughput Identification of Novel Conotoxins from the Vermivorous Oak Cone Snail (Conus quercinus) by Transcriptome Sequencing.

Bingmiao Gao,Qiong Shi,Tian Zhao,Yu Huang,Yabing Zhu,Chao Peng,Yuhui Sun

doi:10.3390/ijms19123901

Abstract

The primary objective of this study was to realize the large-scale discovery of conotoxin sequences from different organs (including the venom duct, venom bulb and salivary gland) of the vermivorous Oak cone snail, Conus quercinus. Using high-throughput transcriptome sequencing, we identified 133 putative conotoxins that belong to 34 known superfamilies, of which nine were previously reported while the remaining 124 were novel conotoxins, with 17 in new and unassigned conotoxin groups. A-, O1-, M-, and I2- superfamilies were the most abundant, and the cysteine frameworks XIII and VIII were observed for the first time in the A- and I2-superfamilies. The transcriptome data from the venom duct, venom bulb and salivary gland showed considerable inter-organizational variations. Each organ had many exclusive conotoxins, and only seven of all the inferred mature peptides were common in the three organs. As expected, most of the identified conotoxins were synthesized in the venom duct at relatively high levels; however, a number of conotoxins were also identified in the venom bulb and the salivary gland with very low transcription levels. Therefore, various organs have different conotoxins with high diversity, suggesting greater contributions from several organs to the high-throughput discovery of new conotoxins for future drug development.

Highlights

Cone snails (Conus spp.) are venomous predators living in tropical marine waters all over the world
65, 55 and 52 putative conotoxin sequences in the VD, SG and VB, respectively, were identified in the worm-hunting species C. quercinus. It appears that most of the identified conotoxins were synthesized in the venom duct at relatively high levels, while many conotoxins were identified in the venom bulb and salivary gland with very low transcription levels
A total of 133 unique conotoxin sequences were identified by using a high-throughput transcriptome sequencing approach

Summary

Introduction

Cone snails (Conus spp.) are venomous predators living in tropical marine waters all over the world They rapidly immobilize their prey using a complex cocktail of small and disulfide-rich peptides, usually 7–46 amino acids (aa) in length and collectively known as conotoxins or conopeptides [1, 2]. Each cone snail is believed to synthesize 50–200 such peptides, and it is estimated that more than 80,000 different conotoxins may exist in approximately 800 species of cone snails around the world [2,3,4] Most of these conotoxins can selectively target certain voltage-gated ion channels, ligand-gated ion channels, G-protein coupled receptors and neurotransmitter transporters in the central and peripheral nervous systems [5,6,7]. The most famous, ω-MVIIA (Ziconotide) is derived from the venom of a fish-hunting species C. magus, and has been approved by the American Food and Drug Administration (FDA)for treatment of chronic pain in patients with cancer or acquired immune deficiency syndrome (AIDS) [8,9]

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