Molecular Phylogeny, Classification and Evolution of Conopeptides
- 670 Downloads
Conopeptides are toxins expressed in the venom duct of cone snails (Conoidea, Conus). These are mostly well-structured peptides and mini-proteins with high potency and selectivity for a broad range of cellular targets. In view of these properties, they are widely used as pharmacological tools and many are candidates for innovative drugs. The conopeptides are primarily classified into superfamilies according to their peptide signal sequence, a classification that is thought to reflect the evolution of the multigenic system. However, this hypothesis has never been thoroughly tested. Here we present a phylogenetic analysis of 1,364 conopeptide signal sequences extracted from GenBank. The results validate the current conopeptide superfamily classification, but also reveal several important new features. The so-called “cysteine-poor” conopeptides are revealed to be closely related to “cysteine-rich” conopeptides; with some of them sharing very similar signal sequences, suggesting that a distinction based on cysteine content and configuration is not phylogenetically relevant and does not reflect the evolutionary history of conopeptides. A given cysteine pattern or pharmacological activity can be found across different superfamilies. Furthermore, a few conopeptides from GenBank do not cluster in any of the known superfamilies, and could represent yet-undefined superfamilies. A clear phylogenetically based classification should help to disentangle the diversity of conopeptides, and could also serve as a rationale to understand the evolution of the toxins in the numerous other species of conoideans and venomous animals at large.
KeywordsCone snails Conus Conoidea Cys-pattern Venom Molecular evolution
We are grateful to the European Commission for financial support. This study has been performed as a part of the CONCO cone snail genome project for health (www.conco.eu) within the 6th Framework Program (LIFESCIHEALTH-6 Integrated Project LSHB-CT-2007, contract number 037592). We are also grateful to Frédérique Lisacek from the Swiss Institute of Bioinformatics for ongoing help. We would like to thank Dr Ron Hogg of OmniScience SA for editorial support.
Conflict of interest
The authors declare that they have no conflict of interest.
- Aguilar MB, Chan de la Rosa RA, Falcon A, Olivera BM, de la Heimer Cotera EP (2009) Peptide pal9a from the venom of the turrid snail Polystira albida from the Gulf of Mexico: purification, characterization, and comparison with P-conotoxin-like (framework IX) conoidean peptides. Peptides 30:467–476PubMedCrossRefGoogle Scholar
- Chang C, Duda TF (2012) Extensive and continuous duplication facilitates rapid evolution and diversification of gene families. Mol Biol Evol. Advance accessGoogle Scholar
- Favreau P, Benoit E, Hocking E, Carlier L, D’hoedt D, Leipold E, Markgraf D, Schlumberger S, Cordova M, Gaertner H, Paolini-Bertrand M, Hartley O, Tytgat J, Heinemann S, Bertrand D, Boelens R, Stöcklin R, Molgo J (2012) A novel mu-conopeptide, CnIIIC, exerts potent and preferential inhibition of NaV1.2/1.4 channels and blocks neuronal nicotinic acetylcholine receptors. Br J Pharmacol (in press)Google Scholar
- Fedosov AE (2007) Anatomy of accessory rhynchodeal organs of Veprecula vepratica and Tritonoturris subrissoides: new types of foregut morphology in Raphitominae (Conoidea). Ruthenica 17:33–41Google Scholar
- Hall TA (1999) BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucleic Acids Symp Ser 41:95–98Google Scholar
- Imperial JS, Kantor Y, Watkins M, Heralde FM, Stevenson B, Chen P, Hansson K, Stenflo J, Ownby J-P, Bouchet P, Olivera BM (2007) Venomous auger snail Hastula (Impages) hectica (Linnaeus 1758): molecular phylogeny, foregut anatomy and comparative toxinology. J Exp Zool 308B:744–756CrossRefGoogle Scholar
- Koua D, Brauer A, Laht S, Kaplinski L, Favreau P, Remm M, Lisacek F, Stöcklin R (2012) ConoDictor: a tool for prediction of conopeptide superfamilies. Nucleic Acids Res (in press)Google Scholar
- Medinskaya AI, Sysoev A (2003) The anatomy of Zemacies excelsa, with a description of a new subfamily of Turridae (Gastropoda, Conoidea). Ruthenica 13:81–87Google Scholar
- Olivera BM, Walker C, Cartier GE, Hooper D, Santos AD, Schoenfeld R, Shetty R, Watkins M, Bandyopadhyay PK, Hillyard DR (1999) Speciation of cone snails and interspecific hyperdivergence of their venom peptides. Potential evolutionary significance of introns. Ann NY Acad Sci 870:223–237PubMedCrossRefGoogle Scholar
- Rambaut A, Drummond AJ (2007) Tracer v1.4. Available from http://beast.bio.ed.ac.uk/Tracer
- Violette A, Leonardi A, Piquemal D, Terrat Y, Biass D, Dutertre S, Noguier F, Ducancel F, Stöcklin R, Križaj I, Favreau P (2012) Recruitment of glycosyl hydrolase proteins in a cone snail venomous arsenal: further insights into biomolecular features of Conus venoms. Mar Drugs 10:258–280PubMedCrossRefGoogle Scholar