Three-fingered RAVERs: Rapid Accumulation of Variations in Exposed Residues of snake venom toxins

Sunagar, Kartik, Jackson, Timothy N. W., Undheim, Elvind A. B., Ali, Syed A., Antunes, Agostinho and Fry, Bryan G. (2013) Three-fingered RAVERs: Rapid Accumulation of Variations in Exposed Residues of snake venom toxins. Toxins, 5 11: 2172-2208. doi:10.3390/toxins5112172


Author Sunagar, Kartik
Jackson, Timothy N. W.
Undheim, Elvind A. B.
Ali, Syed A.
Antunes, Agostinho
Fry, Bryan G.
Title Three-fingered RAVERs: Rapid Accumulation of Variations in Exposed Residues of snake venom toxins
Journal name Toxins   Check publisher's open access policy
ISSN 2072-6651
Publication date 2013-01-01
Year available 2013
Sub-type Article (original research)
DOI 10.3390/toxins5112172
Open Access Status DOI
Volume 5
Issue 11
Start page 2172
End page 2208
Total pages 37
Place of publication Basel, Switzerland
Publisher M D P I AG
Language eng
Subject 3005 Toxicology
2307 Health, Toxicology and Mutagenesis
Abstract Three-finger toxins (3FTx) represent one of the most abundantly secreted and potently toxic components of colubrid (Colubridae), elapid (Elapidae) and psammophid (Psammophiinae subfamily of the Lamprophidae) snake venom arsenal. Despite their conserved structural similarity, they perform a diversity of biological functions. Although they are theorised to undergo adaptive evolution, the underlying diversification mechanisms remain elusive. Here, we report the molecular evolution of different 3FTx functional forms and show that positively selected point mutations have driven the rapid evolution and diversification of 3FTx. These diversification events not only correlate with the evolution of advanced venom delivery systems (VDS) in Caenophidia, but in particular the explosive diversification of the clade subsequent to the evolution of a high pressure, hollow-fanged VDS in elapids, highlighting the significant role of these toxins in the evolution of advanced snakes. We show that Type I, II and III a-neurotoxins have evolved with extreme rapidity under the influence of positive selection. We also show that novel Oxyuranus/Pseudonaja Type II forms lacking the apotypic loop-2 stabilising cysteine doublet characteristic of Type II forms are not phylogenetically basal in relation to other Type IIs as previously thought, but are the result of secondary loss of these apotypic cysteines on at least three separate occasions. Not all 3FTxs have evolved rapidly: κ-neurotoxins, which form non-covalently associated heterodimers, have experienced a relatively weaker influence of diversifying selection; while cytotoxic 3FTx, with their functional sites, dispersed over 40% of the molecular surface, have been extremely constrained by negative selection. We show that the a previous theory of 3FTx molecular evolution (termed ASSET) is evolutionarily implausible and cannot account for the considerable variation observed in very short segments of 3FTx. Instead, we propose a theory of Rapid Accumulation of Variations in Exposed Residues (RAVER) to illustrate the significance of point mutations, guided by focal mutagenesis and positive selection in the evolution and diversification of 3FTx.
Keyword Focal mutagenesis
Positive selection
RAVER
Three finger toxins
Venom evolution
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Biological Sciences Publications
Institute for Molecular Bioscience - Publications
 
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