ArticleMolecular biology and evolution2014
Parallel evolution of tetrodotoxin resistance in three voltage-gated sodium channel genes in the garter snake Thamnophis sirtalis.
Article in Molecular biology and evolution, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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31 citing papers in PubMed, 72 citations in OpenAlex.
- Snakes (Colubridae: Erythrolamprus) With a Complex Toxic Diet Show Convergent yet Highly Heterogeneous Voltage-gated Sodium Channel Evolution.Genome biology and evolution · 2026Article
- Voltage-Gated Sodium Channel Substitutions Underlying Tetrodotoxin Resistance in Nemerteans: Ecological and Evolutionary Implications.International journal of molecular sciences · 2025Article
- The Chemistry and Biology of the Tetrodotoxin Natural Product Family.Angewandte Chemie (International ed. in English) · 2025Review
- 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
- Coevolution with toxic prey produces functional trade-offs in sodium channels of predatory snakes.bioRxiv : the preprint server for biology · 2023Article
- Genomic, transcriptomic, and epigenomic analysis of a medicinal snake,Acta pharmaceutica Sinica. B · 2023Article
- Identification of the NAJournal of chemical ecology · 2023Article
- Convergent evolution of toxin resistance in animals.Biological reviews of the Cambridge Philosophical Society · 2022Review
- Identification of Daboia siamensis venome using integrated multi-omics data.Scientific reports · 2022Article
- The rise of genomics in snake venom research: recent advances and future perspectives.GigaScience · 2022Article
- Form and Function of the Vertebrate and Invertebrate Blood-Brain Barriers.International journal of molecular sciences · 2021Review
- BoaγPLI from Boa constrictor Blood is a Broad-Spectrum Inhibitor of Venom PLAJournal of chemical ecology · 2021Article
- Gene Conversion Facilitates the Adaptive Evolution of Self-Resistance in Highly Toxic Newts.Molecular biology and evolution · 2021Article
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- Adaptive venom evolution and toxicity in octopods is driven by extensive novel gene formation, expansion, and loss.GigaScience · 2020Article
- Parallel Evolution of Two dmrt1-Derived Genes, dmy and dm-W, for Vertebrate Sex Determination.iScience · 2020Article
- The Indian cobra reference genome and transcriptome enables comprehensive identification of venom toxins.Nature genetics · 2020Article
- Genomic Basis of Convergent Island Phenotypes in Boa Constrictors.Genome biology and evolution · 2019Article
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Authors and funding
8 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Members of a gene family expressed in a single species often experience common selection pressures. Consequently, the molecular basis of complex adaptations may be expected to involve parallel evolutionary changes in multiple paralogs. Here, we use bacterial artificial chromosome library scans to investigate the evolution of the voltage-gated sodium channel (Nav) family in the garter snake Thamnophis sirtalis, a predator of highly toxic Taricha newts. Newts possess tetrodotoxin (TTX), which blocks Nav's, arresting action potentials in nerves and muscle. Some Thamnophis populations have evolved resistance to extremely high levels of TTX. Previous work has identified amino acid sites in the skeletal muscle sodium channel Nav1.4 that confer resistance to TTX and vary across populations. We identify parallel evolution of TTX resistance in two additional Nav paralogs, Nav1.6 and 1.7, which are known to be expressed in the peripheral nervous system and should thus be exposed to ingested TTX. Each paralog contains at least one TTX-resistant substitution identical to a substitution previously identified in Nav1.4. These sites are fixed across populations, suggesting that the resistant peripheral nerves antedate resistant muscle. In contrast, three sodium channels expressed solely in the central nervous system (Nav1.1-1.3) showed no evidence of TTX resistance, consistent with protection from toxins by the blood-brain barrier. We also report the exon-intron structure of six Nav paralogs, the first such analysis for snake genes. Our results demonstrate that the molecular basis of adaptation may be both repeatable across members of a gene family and predictable based on functional considerations.
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