The transcriptomic and proteomic basis for the evolution of a novel venom phenotype within the Timber Rattlesnake (Crotalus horridus)

Toxicon. 2015 May;98:34-48. doi: 10.1016/j.toxicon.2015.02.015. Epub 2015 Feb 26.


The genetics underlying adaptive trait evolution describes the intersection between the probability that particular types of mutation are beneficial and the rates they arise. Snake venoms can vary in a directly meaningful manner through coding mutations and regulatory mutations. The amounts of different components determine venom efficacy, but point mutations in coding sequences can also change efficacy and function. The Timber Rattlesnake (Crotalus horridus) has populations that have evolved neurotoxic venom from the typical hemorrhagic rattlesnake venom present throughout most of its range. We identified only a handful of nonsynonymous differences in just five loci between animals with each venom type, and these differences affected lower-abundance toxins. Expression of at least 18 loci encoding hemorrhagic toxins was severely reduced in the production of neurotoxic venom. The entire phospholipase A2 toxin family was completely replaced in the neurotoxic venom, possibly through intergeneric hybridization. Venom paedomorphosis could, at best, explain only some of the loss of expression of hemorrhagic toxins. The number of potential mechanisms for altering venom composition and the patterns observed for C. horridus suggest that rapid venom evolution should occur primarily through changes in venom composition, rather than point mutations affecting coding sequences.

Keywords: Gene expression; Genetics of adaptation; Hybridization; Snake venom; Venom evolution.

Publication types

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

MeSH terms

  • Animals
  • Crotalid Venoms / chemistry*
  • Crotalid Venoms / genetics
  • Crotalus / genetics*
  • Evolution, Molecular*
  • Gene Expression Profiling
  • Gene Library
  • Genetic Loci
  • Phenotype
  • Phospholipases A2 / chemistry
  • Phospholipases A2 / genetics
  • Proteome / metabolism*
  • Sequence Analysis, DNA
  • Toxins, Biological / chemistry*
  • Toxins, Biological / genetics
  • Transcriptome*


  • Crotalid Venoms
  • Proteome
  • Toxins, Biological
  • Phospholipases A2