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. 2005 Mar;15(3):403-20.
doi: 10.1101/gr.3228405.

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

Affiliations

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

Bryan G Fry. Genome Res. 2005 Mar.

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/beta defensin, cystatin, endothelin, factor V, factor X, kallikrein, kunitz-type proteinase inhibitor, LYNX/SLUR, L-amino oxidase, lectin, natriuretic peptide, betanerve growth factor, phospholipase A(2), 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.

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Figures

Figure 1.
Figure 1.
Bayesian analysis of representative (A) acetylcholinesterase and (B) natriuretic related sequences. In order to minimize confusion, all sequences are referred to by their SWISS-PROT accession numbers (http://www.expasy.org/cgi-bin/sprot-search-ful). Snake venom sequences are in bold. Snake body proteins are underlined.
Figure 1.
Figure 1.
Bayesian analysis of representative (A) acetylcholinesterase and (B) natriuretic related sequences. In order to minimize confusion, all sequences are referred to by their SWISS-PROT accession numbers (http://www.expasy.org/cgi-bin/sprot-search-ful). Snake venom sequences are in bold. Snake body proteins are underlined.
Figure 2.
Figure 2.
Bayesian analysis of representative (A) CRISP and (B) complement-related sequences. In order to minimize confusion, all sequences are referred to by their SWISS-PROT accession numbers (http://www.expasy.org/cgi-bin/sprot-search-ful). Snake venom sequences are in bold. Snake body proteins are underlined.
Figure 2.
Figure 2.
Bayesian analysis of representative (A) CRISP and (B) complement-related sequences. In order to minimize confusion, all sequences are referred to by their SWISS-PROT accession numbers (http://www.expasy.org/cgi-bin/sprot-search-ful). Snake venom sequences are in bold. Snake body proteins are underlined.
Figure 3.
Figure 3.
Bayesian analysis of representative (A) crotamine/crotasin/β defensin and (B) factor V related sequences. In order to minimize confusion, all sequences are referred to by their SWISS-PROT accession numbers (http://www.expasy.org/cgi-bin/sprot-search-ful). Snake venom sequences are in bold. Snake body proteins are underlined.
Figure 3.
Figure 3.
Bayesian analysis of representative (A) crotamine/crotasin/β defensin and (B) factor V related sequences. In order to minimize confusion, all sequences are referred to by their SWISS-PROT accession numbers (http://www.expasy.org/cgi-bin/sprot-search-ful). Snake venom sequences are in bold. Snake body proteins are underlined.
Figure 4.
Figure 4.
Bayesian analysis of representative (A) factor X and (B) L-amino oxidase-related sequences. In order to minimize confusion, all sequences are referred to by their SWISS-PROT accession numbers (http://www.expasy.org/cgi-bin/sprot-search-ful). Snake venom sequences are in bold.
Figure 4.
Figure 4.
Bayesian analysis of representative (A) factor X and (B) L-amino oxidase-related sequences. In order to minimize confusion, all sequences are referred to by their SWISS-PROT accession numbers (http://www.expasy.org/cgi-bin/sprot-search-ful). Snake venom sequences are in bold.
Figure 5.
Figure 5.
Bayesian analysis of representative (A) nerve growth factor and (B) phospholipase A2-related sequences. In order to minimize confusion, all sequences are referred to by their SWISS-PROT accession numbers (http://www.expasy.org/cgi-bin/sprot-search-ful). Snake venom sequences are in bold. Snake body proteins are underlined.
Figure 5.
Figure 5.
Bayesian analysis of representative (A) nerve growth factor and (B) phospholipase A2-related sequences. In order to minimize confusion, all sequences are referred to by their SWISS-PROT accession numbers (http://www.expasy.org/cgi-bin/sprot-search-ful). Snake venom sequences are in bold. Snake body proteins are underlined.
Figure 6.
Figure 6.
Bayesian analysis of representative (A) ADAM and (B) AVIT-related sequences. In order to minimize confusion, all sequences are referred to by their SWISS-PROT accession numbers (http://www.expasy.org/cgi-bin/sprot-search-ful). Snake venom sequences are in bold.
Figure 6.
Figure 6.
Bayesian analysis of representative (A) ADAM and (B) AVIT-related sequences. In order to minimize confusion, all sequences are referred to by their SWISS-PROT accession numbers (http://www.expasy.org/cgi-bin/sprot-search-ful). Snake venom sequences are in bold.
Figure 7.
Figure 7.
Bayesian analysis of representative (A) cystatin and (B) sarafotoxin/endothelin-related sequences. In order to minimize confusion, all sequences are referred to by their SWISS-PROT accession numbers (http://www.expasy.org/cgi-bin/sprot-search-ful). Snake venom sequences are in bold.
Figure 7.
Figure 7.
Bayesian analysis of representative (A) cystatin and (B) sarafotoxin/endothelin-related sequences. In order to minimize confusion, all sequences are referred to by their SWISS-PROT accession numbers (http://www.expasy.org/cgi-bin/sprot-search-ful). Snake venom sequences are in bold.
Figure 8.
Figure 8.
Bayesian analysis of representative (A) kallikrein and (B) lectin-related sequences. In order to minimize confusion, all sequences are referred to by their SWISS-PROT accession numbers (http://www.expasy.org/cgi-bin/sprot-search-ful). Snake venom sequences are in bold.
Figure 8.
Figure 8.
Bayesian analysis of representative (A) kallikrein and (B) lectin-related sequences. In order to minimize confusion, all sequences are referred to by their SWISS-PROT accession numbers (http://www.expasy.org/cgi-bin/sprot-search-ful). Snake venom sequences are in bold.
Figure 9.
Figure 9.
Bayesian analysis of representative (A) SPRY and (B) kunitz-type proteinase inhibitor-related sequences. In order to minimize confusion, all sequences are referred to by their SWISS-PROT accession numbers (http://www.expasy.org/cgi-bin/sprot-search-ful). Snake venom sequences are in bold.
Figure 9.
Figure 9.
Bayesian analysis of representative (A) SPRY and (B) kunitz-type proteinase inhibitor-related sequences. In order to minimize confusion, all sequences are referred to by their SWISS-PROT accession numbers (http://www.expasy.org/cgi-bin/sprot-search-ful). Snake venom sequences are in bold.
Figure 10.
Figure 10.
Bayesian analysis of representative (A) 3FTx/LYNX/SLUR and (B) VEGF-related sequences. In order to minimize confusion, all sequences are referred to by their SWISS-PROT accession numbers (http://www.expasy.org/cgi-bin/sprot-search-ful). Snake venom sequences are in bold. Snake body proteins are underlined.
Figure 10.
Figure 10.
Bayesian analysis of representative (A) 3FTx/LYNX/SLUR and (B) VEGF-related sequences. In order to minimize confusion, all sequences are referred to by their SWISS-PROT accession numbers (http://www.expasy.org/cgi-bin/sprot-search-ful). Snake venom sequences are in bold. Snake body proteins are underlined.
Figure 11.
Figure 11.
Molecular phylogenetic analysis of whey acidic proteins/secretory leukoproteinase inhibiting peptides-related sequences (A) Unrooted maximum parsimony network and (B) Outgroup rooted Bayesian analysis. Representative toxin and nontoxin sequences are labeled. In order to minimize confusion, all proteins sequences are referred to by their SWISS-PROT accession numbers (http://www.expasy.org/cgi-bin/sprot-search-ful). Snake venom sequences are in bold.
Figure 11.
Figure 11.
Molecular phylogenetic analysis of whey acidic proteins/secretory leukoproteinase inhibiting peptides-related sequences (A) Unrooted maximum parsimony network and (B) Outgroup rooted Bayesian analysis. Representative toxin and nontoxin sequences are labeled. In order to minimize confusion, all proteins sequences are referred to by their SWISS-PROT accession numbers (http://www.expasy.org/cgi-bin/sprot-search-ful). Snake venom sequences are in bold.

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    1. http://www.expasy.org/tools/blast/; BLAST

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