Targeted sequencing of venom genes from cone snail genomes reveals coupling between dietary breadth and conotoxin diversity

Abstract

Although venomous taxa provide an attractive system to study the genetic basis of adaptation and speciation, the slow pace of toxin gene discovery through traditional laboratory techniques (e.g., cDNA cloning) have limited their utility in the study of ecology and evolution. Here, we applied targeted sequencing techniques to selectively recover venom gene superfamilies and non-toxin loci from the genomes of 32 species of cone snails (family, Conidae), a hyper diverse group of carnivorous marine gastropods that capture their prey using a cocktail of neurotoxic proteins (conotoxins). We were able to successfully recover conotoxin gene superfamilies across all species sequenced in this study with high confidence (> 100X coverage). We found that conotoxin gene superfamilies are composed of 1-6 exons and adjacent noncoding regions are not enriched for simple repetitive elements. Additionally, we provided further evidence for several genetic factors shaping venom composition in cone snails, including positive selection, extensive gene turnover, expression regulation, and potentially, presence-absence variation. Using comparative phylogenetic methods, we found that while diet specificity did not predict patterns of conotoxin gene superfamily size evolution, dietary breadth was positively correlated with total conotoxin gene diversity. These results continue to emphasize the importance of dietary breadth in shaping venom evolution, an underappreciated ecological correlate in venom biology. Finally, the targeted sequencing technique demonstrated here has the potential to radically increase the pace at which venom gene families are sequenced and studied, reshaping our ability to understand the impact of genetic changes on ecologically relevant phenotypes and subsequent diversification.