title: Predictably Convergent Evolution of Sodium Channels in the Arms Race between Predators and Prey.
abstract: Evolution typically arrives at convergent phenotypic solutions to common challenges of natural selection. However, diverse molecular and physiological mechanisms may generate phenotypes that appear similar at the organismal level. How predictable are the molecular mechanisms of adaptation that underlie adaptive convergence? Interactions between toxic prey and their predators provide an excellent avenue to investigate the question of predictability because both taxa must adapt to the presence of defensive poisons. The evolution of resistance to tetrodotoxin (TTX), which binds to and blocks voltage-gated sodium channels (NaV1) in nerves and muscle, has been remarkably parallel across deep phylogenetic divides. In both predators and prey, representing three major vertebrate groups, TTX resistance has arisen through structural changes in NaV1 proteins. Fish, amphibians and reptiles, though they differ in the total number of NaV1 paralogs in their genomes, have each evolved common amino acid substitutions in the orthologous skeletal muscle NaV1.4. Many of these substitutions involve not only the same positions in the protein, but also the identical amino acid residues. Similarly, predictable convergence is observed across the family of sodium channel genes expressed in different tissues in puffer fish and in garter snakes. Trade-offs between the fundamental role of NaV1 proteins in selective permeability of Na+ and their ability to resist binding by TTX generate a highly constrained adaptive landscape at the level of the protein.
authors.affiliation: Department of Biology and Mountain Lake Biological Station, University of Virginia, Charlottesville, Va., USA.
authors.forename: Edmund D
authors.initials: ED
authors.lastname: Brodie
authors.forename: Edmund D
authors.initials: ED
authors.lastname: Brodie
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D005075:Biological Evolution; D008958:Models, Molecular; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D011235:Predatory Behavior / Q000502:physiology*; D012641:Selection, Genetic; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000235:genetics / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D026941:Sodium Channel Blockers; D015222:Sodium Channels; D013779:Tetrodotoxin