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. 2014 Feb 5;9(2):e87648.
doi: 10.1371/journal.pone.0087648. eCollection 2014.

Diversity of conotoxin gene superfamilies in the venomous snail, Conus victoriae

Samuel D Robinson  1 , Helena Safavi-Hemami  2 , Lachlan D McIntosh  3 , Anthony W Purcell  2 , Raymond S Norton  1 , Anthony T Papenfuss  3
Affiliations

Diversity of conotoxin gene superfamilies in the venomous snail, Conus victoriae

Samuel D Robinson et al. PLoS One. .

Abstract

Animal venoms represent a vast library of bioactive peptides and proteins with proven potential, not only as research tools but also as drug leads and therapeutics. This is illustrated clearly by marine cone snails (genus Conus), whose venoms consist of mixtures of hundreds of peptides (conotoxins) with a diverse array of molecular targets, including voltage- and ligand-gated ion channels, G-protein coupled receptors and neurotransmitter transporters. Several conotoxins have found applications as research tools, with some being used or developed as therapeutics. The primary objective of this study was the large-scale discovery of conotoxin sequences from the venom gland of an Australian cone snail species, Conus victoriae. Using cDNA library normalization, high-throughput 454 sequencing, de novo transcriptome assembly and annotation with BLASTX and profile hidden Markov models, we discovered over 100 unique conotoxin sequences from 20 gene superfamilies, the highest diversity of conotoxins so far reported in a single study. Many of the sequences identified are new members of known conotoxin superfamilies, some help to redefine these superfamilies and others represent altogether new classes of conotoxins. In addition, we have demonstrated an efficient combination of methods to mine an animal venom gland and generate a library of sequences encoding bioactive peptides.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Translated C. victoriae A-superfamily precursor sequences.
*, Vc1.2 precursor shown for comparison is in grey; Cys, yellow; Predicted signal peptides are underlined in purple and the predicted mature peptides are underlined in black, while that of Vc1.2 is underlined in grey. This color scheme is used in all subsequent figures.
Figure 2
Figure 2. Translated C. victoriae I1-superfamily (A), I2-superfamily (B) and I4-superfamily (C) precursor sequences.
*, M11.2 mature peptide , Ep11.1 precursor, ViTx precursor , Gla-TxX precursor and the I3-superfamily (D) precursor Ca11a shown for comparison.
Figure 3
Figure 3. Translated C. victoriae J-superfamily (A), M-superfamily (B), M-conomarphin (C) precursor sequences.
*, pl14a , Tx3.2 (tx3a) , TxMMSK-05 , LtIIIA , conomarphin , Mr038 precursors shown for comparison.
Figure 4
Figure 4. Translated C. victoriae O1-superfamily precursor sequences.
*, Vc6.1, Vc6.3, Vc6.4, Vc6.6 and MrVIB shown for comparison.
Figure 5
Figure 5. Translated C. victoriae O2-superfamily (A) and contryphan (B) precursor sequences.
*, TxVIIA , and contryphan-R/Tx precursors shown for comparison.
Figure 6
Figure 6. Translated C. victoriae O3-superfamily (A), P-superfamily (B) and S-superfamily (C) precursor sequences.
*, Bromosleeper peptide (GenBank: GQ981406.1) , Gm9.1 (GmIXA) , Tx8.1 , GVIIIA and RVIIIA precursors shown for comparison.
Figure 7
Figure 7. Translated C. victoriae T-superfamily precursor sequences.
*, Vc5.4 , TxVA , TxXIIIA , and χ-MrIA precursors shown for comparison.
Figure 8
Figure 8. Translated C. victoriae conantokin (A), con-ikot-ikot (B), conodipine (C) and B2-superfamily (D) precursor sequences.
*, Con-Gm , G56 , con-ikot-ikot , p21a , Conodipine-M and B2-superfamily sequences from C. literratus and C. consors are shown for comparison. The conodipine catalytic His-Asp dyad is boxed in red.
Figure 9
Figure 9. Translated C. victoriae E-superfamily (A), F-superfamily (B), H-superfamily (C) and U-superfamily (D) precursor sequences.
*, Mr104 , Mr105 , other H-superfamily precursors (Mr097, Mr098, Mr099 and Mr100) and the textile convulsant peptide are shown for comparison.
Figure 10
Figure 10. C. victoriae Hhe53-like open reading frame displaying translation of forward frames 1 and 2.
Possible initiator codon in frame 2 is underlined in purple and the sequence encoding the predicted mature peptide in frame 1 is underlined in black.
Figure 11
Figure 11. Relative abundance of conotoxin superfamilies (total reads assembled for conotoxin precursors of each superfamily).
High abundance reads may be under-represented as a result of cDNA library normalization.
See this image and copyright information in PMC

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