From genome to “venome”: Molecular origin and evolution of the snake venom proteome inferred from phylogenetic analysis of toxin sequences and related body proteins

  1. Bryan G. Fry
  1. Australian Venom Research Unit, Level 8, School of Medicine, University of Melbourne, Parkville, Victoria 3010 Australia; SWISS-PROT Group, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD, United Kingdom

Abstract

This study analyzed the origin and evolution of snake venom proteome by means of phylogenetic analysis of the amino acid sequences of the toxins and related nonvenom proteins. The snake toxins were shown to have arisen from recruitment events of genes from within the following protein families: acetylcholinesterase, ADAM (disintegrin/metalloproteinase), AVIT, complement C3, crotasin/β defensin, cystatin, endothelin, factor V, factor X, kallikrein, kunitz-type proteinase inhibitor, LYNX/SLUR, L-amino oxidase, lectin, natriuretic peptide, βnerve growth factor, phospholipase A2, SPla/Ryanodine, vascular endothelial growth factor, and whey acidic protein/secretory leukoproteinase inhibitor. Toxin recruitment events were found to have occurred at least 24 times in the evolution of snake venom. Two of these toxin derivations (CRISP and kallikrein toxins) appear to have been actually the result of modifications of existing salivary proteins rather than gene recruitment events. One snake toxin type, the waglerin peptides from Tropidolaemus wagleri (Wagler's Viper), did not have a match with known proteins and may be derived from a uniquely reptilian peptide. All of the snake toxin types still possess the bioactivity of the ancestral proteins in at least some of the toxin isoforms. However, this study revealed that the toxin types, where the ancestral protein was extensively cysteine cross-linked, were the ones that flourished into functionally diverse, novel toxin multigene families.

Footnotes

  • Article and publication are at http://www.genome.org/cgi/doi/10.1101/gr.3228405.

  • [Supplemental material is available online at www.genome.org.]

  • E-mail bgf{at}unimelb.edu.au; fax 61-3-93482048.

    • Accepted January 4, 2005.
    • Received September 5, 2004.
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