ArticleMolecular biology and evolution2018
A Single Mutation Unlocks Cascading Exaptations in the Origin of a Potent Pitviper Neurotoxin.
Article in Molecular biology and evolution, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 33 citations in OpenAlex.
- Sexual Dimorphism and Intraspecific Toxin Variation in Crotalus durissus terrificus Venom: Insights from Proteomics, Peptidomics, and Structural Modeling.Journal of proteome research · 2026Article
- Molecular mechanisms underlying early functional divergence in snake venom inferred from the genomes of two pitviper lineages.BMC biology · 2025Article
- Tandem Duplication of Serpin Genes Yields Functional Variation and Snake Venom Inhibitors.Molecular biology and evolution · 2025Article
- Variations in "Functional Site" Residues and Classification of Three-Finger Neurotoxins in Snake Venoms.Toxins · 2025Review
- Snake Venomics of the Arboreal Talamancan Palm-Pitviper,Journal of proteome research · 2025Article
- A Segregating Structural Variant Defines Novel Venom Phenotypes in the Eastern Diamondback Rattlesnake.Molecular biology and evolution · 2025Article
- Sequence Divergence in Venom Genes Within and Between Montane Pitviper (Viperidae: Crotalinae: Cerrophidion) Species is Driven by Mutation-Drift Equilibrium.Journal of molecular evolution · 2023Article
- Genomic, transcriptomic, and epigenomic analysis of a medicinal snake,Acta pharmaceutica Sinica. B · 2023Article
- Venom Gene Sequence Diversity and Expression Jointly Shape Diet Adaptation in Pitvipers.Molecular biology and evolution · 2022Article
- A symphony of destruction: Dynamic differential fibrinogenolytic toxicity by rattlesnake (Crotalus and Sistrurus) venoms.Comparative biochemistry and physiology. Toxicology & pharmacology : CBP · 2021Article
- Article
- Phylogenetically diverse diets favor more complex venoms in North American pitvipers.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- The origin and diversification of a novel protein family in venomous snakes.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Activity of two key toxin groups in Australian elapid venoms show a strong correlation to phylogeny but not to diet.BMC evolutionary biology · 2020Article
- How the Toxin got its Toxicity.Frontiers in pharmacology · 2020Article
- Article
- Comparative venom-gland transcriptomics and venom proteomics of four Sidewinder Rattlesnake (Crotalus cerastes) lineages reveal little differential expression despite individual variation.Scientific reports · 2018Article
- Three-Finger Toxin Diversification in the Venoms of Cat-Eye Snakes (Colubridae: Boiga).Journal of molecular evolution · 2018Article
- Adaptive evolution of distinct prey-specific toxin genes in rear-fanged snake venom.Proceedings. Biological sciences · 2018Article
- Phenotypic Variation in Mojave Rattlesnake (Crotalus scutulatus) Venom Is Driven by Four Toxin Families.Toxins · 2018Article
Corrections and comments
- Erratum issued
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Evolutionary innovations and complex phenotypes seemingly require an improbable amount of genetic change to evolve. Rattlesnakes display two dramatically different venom phenotypes. Type I venoms are hemorrhagic with low systemic toxicity and high expression of tissue-destroying snake venom metalloproteinases. Type II venoms are highly neurotoxic and lack snake venom metalloproteinase expression and associated hemorrhagic activity. This dichotomy hinges on Mojave toxin (MTx), a phospholipase A2 (PLA2) based β-neurotoxin expressed in Type II venoms. MTx is comprised of a nontoxic acidic subunit that undergoes extensive proteolytic processing and allosterically regulates activity of a neurotoxic basic subunit. Evolution of the acidic subunit presents an evolutionary challenge because the need for high expression of a nontoxic venom component and the proteolytic machinery required for processing suggests genetic changes of seemingly little immediate benefit to fitness. We showed that MTx evolved through a cascading series of exaptations unlocked by a single nucleotide change. The evolution of one new cleavage site in the acidic subunit unmasked buried cleavage sites already present in ancestral PLA2s, enabling proteolytic processing. Snake venom serine proteases, already present in the venom to disrupt prey hemostasis, possess the requisite specificities for MTx acidic subunit proteolysis. The dimerization interface between MTx subunits evolved by exploiting a latent, but masked, hydrophobic interaction between ancestral PLA2s. The evolution of MTx through exaptation of existing functional and structural features suggests complex phenotypes that depend on evolutionary innovations can arise from minimal genetic change enabled by prior evolution.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.