Elucidation of the molecular envenomation strategy of the cone snail Conus geographus through transcriptome sequencing of its venom duct

Hao Hu,Baldomero M Olivera,Pradip K Bandyopadhyay,Mark Yandell

doi:10.1186/1471-2164-13-284

Abstract

BackgroundThe fish-hunting cone snail, Conus geographus, is the deadliest snail on earth. In the absence of medical intervention, 70% of human stinging cases are fatal. Although, its venom is known to consist of a cocktail of small peptides targeting different ion-channels and receptors, the bulk of its venom constituents, their sites of manufacture, relative abundances and how they function collectively in envenomation has remained unknown.ResultsWe have used transcriptome sequencing to systematically elucidate the contents the C. geographus venom duct, dividing it into four segments in order to investigate each segment’s mRNA contents. Three different types of calcium channel (each targeted by unrelated, entirely distinct venom peptides) and at least two different nicotinic receptors appear to be targeted by the venom. Moreover, the most highly expressed venom component is not paralytic, but causes sensory disorientation and is expressed in a different segment of the venom duct from venoms believed to cause sensory disruption. We have also identified several new toxins of interest for pharmaceutical and neuroscience research.ConclusionsConus geographus is believed to prey on fish hiding in reef crevices at night. Our data suggest that disorientation of prey is central to its envenomation strategy. Furthermore, venom expression profiles also suggest a sophisticated layering of venom-expression patterns within the venom duct, with disorientating and paralytic venoms expressed in different regions. Thus, our transcriptome analysis provides a new physiological framework for understanding the molecular envenomation strategy of this deadly snail.

Highlights

The fish-hunting cone snail, Conus geographus, is the deadliest snail on earth
In the absence of medical intervention, 70% of human stinging cases are fatal [11]. The venom of this cone snail species was the first that was comprehensively analyzed; it was the characterization of Conus geographus venom peptides which established that most of the biologically-active components of Conus venoms, were small, disulfide rich peptides [12]
We show that there exists clear transcriptional compartmentalization of the venom duct, with marked region-specific synthesis of conotoxins, and for many other types of genes as well, such as insulin-like growth factors, which are highly expressed

Summary

Introduction

The fish-hunting cone snail, Conus geographus, is the deadliest snail on earth. In the absence of medical intervention, 70% of human stinging cases are fatal. Cone snails are venomous predators that rapidly immobilize their prey using a complex cocktail of short peptides (10–40 AA long) collectively known as conotoxins. Most of these peptides, are targeted with exquisite specificity to receptors, ion channels, and transporters in the nervous system [1,2,3,4]. We have analyzed the venom-duct of Conus geographus using a transcriptomics approach This species, widely known as the geography cone, is well known as the deadliest of all cone snail species, responsible for most of the human fatalities recorded in the medical literature. The venom of this cone snail species was the first that was comprehensively analyzed; it was the characterization of Conus geographus venom peptides which established that most of the biologically-active components of Conus venoms, were small, disulfide rich peptides [12]

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Conclusion