From genome to “venome”: Molecular origin and evolution of the snake venom proteome inferred from phylogenetic analysis of toxin sequences and related body proteins
Open accessAbstract
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 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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Duplications in beta-defensin, C-type natriuretic peptide and nerve growth factor gene families have also occurred independently in reptiles during evolution of their venom.
“Notably, duplications in each of the b -defensin, C-type natriuretic peptide and nerve growth factor gene families have also occurred independently in reptiles during the evolution of their venom 47 .”
From Genome analysis of the platypus reveals unique signatures of evolution (2008) · cites this paper as [47]
The paper’s opening summary identifies β-defensin/crotasin, natriuretic peptide, and nerve growth factor among the protein families recruited into snake venom. The Molecular scaffold characteristics section discusses toxin multigene families, but the passages do not establish that each of these three families underwent an independent gene duplication in reptiles during venom evolution. (LLM, conf=0.82)
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- Authors
- Fry, B. G.
- Affiliations
- European Bioinformatics Institute (GB)
- Corresponding author
- Fry, Bryan G.
- ORCID
- Fry, Bryan G.
- Venue
- Genome Research
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2005-03
- Volume
- 15
- Issue
- 3
- Pages
- 403-420
- ISSN
- 1088-9051 (ISSN-L)
- PMC
- PMC551567
- OpenAlex
- W2073555092
- Cited by
- 486
- References
- 45
- Citations by year
- 2026: 9 · 2025: 19 · 2024: 14 · 2023: 9 · 2022: 20 · 2021: 20 · 2020: 27 · 2019: 23 · 2018: 14 · 2017: 30 · 2016: 29 · 2015: 23 · 2014: 40 · 2013: 30 · 2012: 21
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genome Research (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- European Bioinformatics Institute
- Australian Academy of Science
- University of Melbourne
- Australian Research Council (DP0451663)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Venomous Animal Envenomation and Studies
- Physical Sciences › Environmental Science › Global and Planetary Change › Amphibian and Reptile Biology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Keywords
- snake venom proteome, gene recruitment, acetylcholinesterase, Adam, kallikrein, phospholipase A2, cysteine cross-linking, salivary proteins
- MeSH terms
- Animals, Phylogeny, Snake Venoms, Snakes, Tissue Distribution, Evolution, Molecular, Proteome
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