ArticleProceedings of the National Academy of Sciences of the United States of America2012
Constraint shapes convergence in tetrodotoxin-resistant sodium channels of snakes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 1 of them a synthesis that pooled it.
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Who cites it
68 citing papers in PubMed, 1 synthesis or guideline pooled it, 183 citations in OpenAlex.
- The probability of genetic parallelism and convergence in natural populations.Proceedings. Biological sciences · 2012Pooled it
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- A designer saxitoxin-engineered sodium channel pair as a general tool for subtype-selective inhibition.Cell chemical biology · 2026Article
- The genetic foundations of convergent traits.Nature reviews. Genetics · 2026Review
- Ingestion of the potent neurotoxin epibatidine does not compromise locomotion or behavior in the poison frogbioRxiv : the preprint server for biology · 2026Article
- Snakes (Colubridae: Erythrolamprus) With a Complex Toxic Diet Show Convergent yet Highly Heterogeneous Voltage-gated Sodium Channel Evolution.Genome biology and evolution · 2026Article
- Phenotypic complexity determines the predictability of molecular convergence.bioRxiv : the preprint server for biology · 2026Article
- Structural and evolutionary constraints of organophosphate resistance in dipteran carboxylesterases.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- RECUR: identifying recurrent amino acid substitutions from multiple sequence alignments.Molecular biology and evolution · 2026Article
- Voltage-Gated Sodium Channel Substitutions Underlying Tetrodotoxin Resistance in Nemerteans: Ecological and Evolutionary Implications.International journal of molecular sciences · 2025Article
- A chemogenetic ligand-receptor pair for voltage-gated sodium channel subtype-selective inhibition.bioRxiv : the preprint server for biology · 2025Article
- Convergent evolution of noncoding elements associated with short tarsus length in birds.BMC biology · 2025Article
- Genetic Architecture, Spatial Heterogeneity, and the Arms Race between Newts and Snakes: Exploring Coevolution with Simulations.The American naturalist · 2025Article
- Where Does All the Poison Go? Investigating Toxicokinetics of Newt (Taricha) Tetrodotoxin (TTX) in Garter Snakes (Thamnophis).Journal of chemical ecology · 2024Article
- Sodium Channel β Subunits-An Additional Element in Animal Tetrodotoxin Resistance?International journal of molecular sciences · 2024Article
- Independently evolved pollution resistance in four killifish populations is largely explained by few variants of large effect.Evolutionary applications · 2024Article
- Coevolution with toxic prey produces functional trade-offs in sodium channels of predatory snakes.bioRxiv : the preprint server for biology · 2023Article
- Selection-driven trait loss in independently evolved cavefish populations.Nature communications · 2023Article
- Genomic, transcriptomic, and epigenomic analysis of a medicinal snake,Acta pharmaceutica Sinica. B · 2023Article
- Genomic signatures of recent convergent transitions to social life in spiders.Nature communications · 2022Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Natural selection often produces convergent changes in unrelated lineages, but the degree to which such adaptations occur via predictable genetic paths is unknown. If only a limited subset of possible mutations is fixed in independent lineages, then it is clear that constraint in the production or function of molecular variants is an important determinant of adaptation. We demonstrate remarkably constrained convergence during the evolution of resistance to the lethal poison, tetrodotoxin, in six snake species representing three distinct lineages from around the globe. Resistance-conferring amino acid substitutions in a voltage-gated sodium channel, Na(v)1.4, are clustered in only two regions of the protein, and a majority of the replacements are confined to the same three positions. The observed changes represent only a small fraction of the experimentally validated mutations known to increase Na(v)1.4 resistance to tetrodotoxin. These results suggest that constraints resulting from functional tradeoffs between ion channel function and toxin resistance led to predictable patterns of evolutionary convergence at the molecular level. Our data are consistent with theoretical predictions and recent microcosm work that suggest a predictable path is followed during an adaptive walk along a mutational landscape, and that natural selection may be frequently constrained to produce similar genetic outcomes even when operating on independent lineages.
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