Diversity of conotoxin types from Conus californicus reflects a diversity of prey types and a novel evolutionary history

Abstract

Most species within the genus Conus are considered to be specialists in their consumption of prey, typically feeding on molluscs, vermiform invertebrates or fish, and employ peptide toxins to immobilize prey. Conus californicus Hinds 1844 atypically utilizes a wide range of food sources from all three groups. Using DNA- and protein-based methods, we analyzed the molecular diversity of C. californicus toxins and detected a correspondingly large number of conotoxin types. We identified cDNAs corresponding to seven known cysteine-frameworks containing over 40 individual inferred peptides. Additionally, we found a new framework (22) with six predicted peptide examples, along with two forms of a new peptide type of unusual length. Analysis of leader sequences allowed assignment to known superfamilies in only half of the cases, and several of these showed a framework that was not in congruence with the identified superfamily. Mass spectrometric examination of chromatographic fractions from whole venom served to identify peptides corresponding to a number of cDNAs, in several cases differing in their degree of posttranslational modification. This suggests differential or incomplete biochemical processing of these peptides. In general, it is difficult to fit conotoxins from C. californicus into established toxin classification schemes. We hypothesize that the novel structural modifications of individual peptides and their encoding genes reflect evolutionary adaptation to prey species of an unusually wide range as well as the large phylogenetic distance between C. californicus and Indo-Pacific species.

High Conopeptide Diversity in Conus tribblei Revealed Through Analysis of Venom Duct Transcriptome Using Two High-Throughput Sequencing Platforms

“…Two conopeptides showing 41–44% sequence identity to the signal region of V-superfamily were classified as V-like group. These conopeptides contained cysteine patterns VI/VII (C-C-CC-C-C) (Olivera et al 1984) and XXII (C-C-C-C-C-C-C-C) (Elliger et al 2011). Also, two sequences showing similarity at the mature region to the conopeptide recently classified as Y2 superfamily (Lavergne et al 2013) were also identified.…”

“…It is believed that the generalist feeding behaviour of C. californicus has promoted the expression of extremely diverse conopeptides in this species that could not be classified according to the typical established gene superfamilies (Elliger et al 2011), while the specialized diet of Conus leopardus has significantly decreased the diversity of the expressed conopeptides (Remigio and Duda 2008). Therefore, the presence of diverse conopeptides in the venom duct of C. tribblei may reflect its wide range of prey preferences.…”

“…High-throughput sequencing can achieve higher sequencing depth and greater coverage of transcriptome so that even rare transcripts with low expression levels can be identified, providing a more accurate resolution of the conopeptide diversity in cone snails. In fact, identification of diverse conopeptides is not limited to the species in the major clade of Conus ; the survey of the Conus californicus venom duct showed significant conopeptide diversity in this phylogenetically distant species (Biggs et al 2010; Elliger et al 2011). Thus, identification of conopeptides in distinct clades of Conus will facilitate understanding the evolution and diversification mechanisms of the conopeptide genes.…”

A Conus regularis Conotoxin with a Novel Eight-Cysteine Framework Inhibits CaV2.2 Channels and Displays an Anti-Nociceptive Activity

“…In fact, with the identification of RsXXIVA, only seven different peptides with four disulfide bonds have been reported [25,26,27,28,29,30]. The most extensively studied four disulfide bond conotoxin group is the I-superfamily group [31].…”

Characterization of a T-superfamily conotoxin TxVC from Conus textile that selectively targets neuronal nAChR subtypes

“…They selectively interact with Na + channels, presynaptic Ca 2+ channels or G protein-coupled presynaptic receptors in general [4,5]. However, we isolated a T-superfamily conotoxin TxVC (KPCCSIHDNSCCGL-NH 2 ) from C. textile years ago, determined its peptide sequence by Edman method [6], investigated its disulfide bond configuration using the synthesized peptide, and then surprisingly found that this TxVC selectively interacted with neuronal nicotinic acetylcholine receptor (nAChR) subtype a4b2 and a3b2 without obvious pharmacological effects on voltage-gated K + , Na + and Ca 2+ ion channels in DRG cells.…”