Transcriptomic messiness in the venom duct of Conus miles contributes to conotoxin diversity

Jin, Ai-Hua, Dutertre, Sébastien, Kaas, Quentin, Lavergne, Vincent, Kubala, Petra, Lewis, Richard J. and Alewood, Paul F. (2013) Transcriptomic messiness in the venom duct of Conus miles contributes to conotoxin diversity. Molecular and Cellular Proteomics, 12 12: 3824-3833. doi:10.1074/mcp.M113.030353

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Author Jin, Ai-Hua
Dutertre, Sébastien
Kaas, Quentin
Lavergne, Vincent
Kubala, Petra
Lewis, Richard J.
Alewood, Paul F.
Title Transcriptomic messiness in the venom duct of Conus miles contributes to conotoxin diversity
Formatted title
Transcriptomic messiness in the venom duct of Conus miles contributes to conotoxin diversity
Journal name Molecular and Cellular Proteomics   Check publisher's open access policy
ISSN 1535-9476
Publication date 2013-12-01
Sub-type Article (original research)
DOI 10.1074/mcp.M113.030353
Volume 12
Issue 12
Start page 3824
End page 3833
Total pages 10
Place of publication Bethesda, MD, United States
Publisher American Society for Biochemistry and Molecular Biology
Collection year 2014
Language eng
Formatted abstract
Marine cone snails have developed sophisticated chemical strategies to capture prey and defend against predators. Among the vast array of bioactive molecules in their venom, the peptide components called conotoxins or conopeptides dominate, with many binding with high affinity and selectivity to a broad range of cellular targets, including receptors and transporters of the nervous system. Whereas, the conopeptide gene precursor organisation has a conserved topology, the peptides in the venom duct are highly processed. Indeed, deep sequencing transcriptomics has uncovered on average less than 100 toxin gene precursors per species, while advanced proteomics has revealed > 10-fold greater diversity at the peptide level. In the present study, second generation sequencing technologies coupled to highly sensitive mass spectrometry methods were applied to rapidly uncover the conopeptide diversity in the venom of a worm hunting species, Conus miles. A total of 662 putative conopeptide encoded sequences were retrieved from transcriptomic data, comprising 48 validated conotoxin sequences that clustered into 10 gene superfamilies, including 3 novel superfamilies and a novel cysteine framework (C-C-C-CCC-C-C) identified at both transcript and peptide levels. A surprisingly large number of conopeptide gene sequences were 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 generate alternative cleavage sites, interrupted or elongated cysteine frameworks, and highly variable isoforms within families that could be identified at the peptide level. Together with the variable peptide processing identified previously, background genetic and phenotypic levels of biological messiness in venoms contributes to the hypervariability of venom peptides and their ability to rapidly evolve.
Keyword Conopeptide
Mass spectrometry
Venom transcriptome
454 Sequencing
Cone snail venom
Conus miles
Bioinformatics searching
Mass spectrometry
Molecular evolution
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes First Published on September 16, 2013.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 24 times in Thomson Reuters Web of Science Article | Citations
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Created: Thu, 21 Nov 2013, 10:18:22 EST by Susan Allen on behalf of Institute for Molecular Bioscience