Evolutionary diversification of TTX-resistant sodium channels in a predator-prey interaction

Nature. 2005 Apr 7;434(7034):759-63. doi: 10.1038/nature03444.


Understanding the molecular genetic basis of adaptations provides incomparable insight into the genetic mechanisms by which evolutionary diversification takes place. Whether the evolution of common traits in different lineages proceeds by similar or unique mutations, and the degree to which phenotypic evolution is controlled by changes in gene regulation as opposed to gene function, are fundamental questions in evolutionary biology that require such an understanding of genetic mechanisms. Here we identify novel changes in the molecular structure of a sodium channel expressed in snake skeletal muscle, tsNa(V)1.4, that are responsible for differences in tetrodotoxin (TTX) resistance among garter snake populations coevolving with toxic newts. By the functional expression of tsNa(V)1.4, we show how differences in the amino-acid sequence of the channel affect TTX binding and impart different levels of resistance in four snake populations. These results indicate that the evolution of a physiological trait has occurred through a series of unique functional changes in a gene that is otherwise highly conserved among vertebrates.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptation, Physiological
  • Amino Acid Sequence
  • Animals
  • Biological Evolution*
  • Colubridae / genetics
  • Colubridae / metabolism
  • Colubridae / physiology*
  • Dose-Response Relationship, Drug
  • Drug Resistance*
  • Electric Conductivity
  • Humans
  • Molecular Sequence Data
  • Muscle, Skeletal / metabolism
  • Oocytes / drug effects
  • Oocytes / metabolism
  • Phylogeny
  • Predatory Behavior / physiology*
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Salamandridae / physiology*
  • Sodium / metabolism
  • Sodium Channel Blockers / metabolism
  • Sodium Channel Blockers / pharmacology
  • Sodium Channels / chemistry
  • Sodium Channels / genetics
  • Sodium Channels / metabolism*
  • Tetrodotoxin / metabolism
  • Tetrodotoxin / pharmacology*
  • Xenopus laevis


  • RNA, Messenger
  • Recombinant Fusion Proteins
  • Sodium Channel Blockers
  • Sodium Channels
  • Tetrodotoxin
  • Sodium

Associated data

  • GENBANK/AY851743
  • GENBANK/AY851744
  • GENBANK/AY851745
  • GENBANK/AY851746