Oral Presentation 10th Australian Peptide Conference 2013

Conotoxin evolution gets messy (#16)

Aihua JIN 1 , Sebastien Dutertre 1 , Quentin Kaas 1 , Vincent Lavergne 1 , Petra Kubala 1 , Alun Jones 1 , Richard J Lewis 1 , Paul F Alewood 1
  1. Institute for Molecular Bioscience, St Lucia, QLD, Australia
Cone snail venom comprises many 1000s of venom peptides that have evolved for prey capture and defence from a smaller set of transcriptomic sequences. Deep venomics has revealed surprising messiness in the venom at the proteomic level that arises from variable peptide processing by endoproteases. This “messy” processing generates ragged N- and C-terminal processing underlying much of the peptide diversity found at low levels using high sensitivity LC/MS techniques, in addition to a smaller number of predicted major cleavage products. Recently, we have uncovered another layer of venom peptide messiness seen at the transcriptomic level in cone snails. A surprisingly large number of conopeptide gene sequences were found to be expressed at low-levels, including a series of single amino acid variants, as well as sequences containing deletions and frame and stop codon shifts. Some of the toxin variants generated alternative cleavage sites, interrupted or elongated cysteine frameworks, and highly variable isoforms within families that could be identified at the peptide level. Together with variable peptide processing, this background biological messiness explains the hypervariability of venom peptides. Variable processing and transcriptomic messiness likely contributes to the rapidly evolution of venoms with new or altered function and might be exploited in non-venomous species and prove useful in expanding structure-function studies.