Deconstructing a complex molecular phenotype: population-level variation in individual venom proteins in Eastern Massasauga Rattlesnakes (Sistrurus c. catenatus)

J Mol Evol. 2011 Apr;72(4):383-97. doi: 10.1007/s00239-011-9437-4. Epub 2011 Mar 11.


Identifying the molecular basis for complex adaptations such as the toxic proteins used by venomous snakes to subdue and digest prey is an important step in understanding the evolutionary and functional basis for such traits. Recent proteomics-based analyses have made possible the identification of all constituent proteins in whole venom samples. Here we exploit this advance to study patterns of population-level variation in venom proteins from 254 adult eastern massasauga rattlesnakes (Sistrurus c. catenatus) collected from 10 populations. Analysis of presence-absence variation in specific proteins from 1D PAGE gels shows that: (1) The frequency spectra for individual protein bands is U-shaped with a large number of specific proteins either being consistently "common" or "rare" across populations possibly reflecting functional differences. (2) Multivariate axes which summarize whole venom variation consist of bands from all major types of proteins implying the integration of functionally distinct components within the overall venom phenotype. (3) There is significant differentiation in venom proteins across populations and the specific classes of proteins contributing to this differentiation have been identified. (4) Levels of population differentiation in venom proteins are not correlated with levels of neutral genetic differentiation, or genetically effective population sizes which argues that patterns of venom variation are not simply a consequence of population structure but leaves open the role of selection in generating population differences in venom. Our results identify particular classes of venom proteins and their associated genes as being fruitful targets for future studies of the molecular and functional basis for this complex adaptive phenotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Appalachian Region
  • Crotalid Venoms / chemistry*
  • Crotalid Venoms / classification
  • Crotalid Venoms / genetics
  • Crotalid Venoms / metabolism
  • Crotalus / classification
  • Crotalus / genetics
  • Crotalus / metabolism*
  • Electrophoresis, Polyacrylamide Gel
  • Genetic Variation
  • Genetics, Population
  • Illinois
  • Ontario
  • Phenotype
  • Proteins / chemistry*
  • Proteins / classification
  • Proteins / genetics
  • Proteomics / methods
  • Statistics, Nonparametric


  • Crotalid Venoms
  • Proteins