Article

Journal of Molecular Evolution

, Volume 57, Issue 4, pp 446-452

Isolation of a Neurotoxin (α-colubritoxin) from a Nonvenomous Colubrid: Evidence for Early Origin of Venom in Snakes

  • Bryan G. FryAffiliated withDepartment of Biological Sciences, Faculty of Science, National University of Singapore, 119260 Australian Venom Research Unit, Department of Pharmacology, University of Melbourne, Parkville, Victoria 3010 Email author 
  • , Natalie G. LumsdenAffiliated withMonash Venom Group, Department of Pharmacology, Monash University, Victoria 3800
  • , Wolfgang WüsterAffiliated withSchool of Biological Sciences, University of Wales, Bangor, LL57 2UW, Wales
  • , Janith C. WickramaratnaAffiliated withMonash Venom Group, Department of Pharmacology, Monash University, Victoria 3800
  • , Wayne C. HodgsonAffiliated withMonash Venom Group, Department of Pharmacology, Monash University, Victoria 3800
  • , R. Manjunatha KiniAffiliated withDepartment of Biological Sciences, Faculty of Science, National University of Singapore, 119260

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Abstract

The evolution of venom in advanced snakes has been a focus of long-standing interest. Here we provide the first complete amino acid sequence of a colubrid toxin, which we have called α-colubritoxin, isolated from the Asian ratsnake Coelognathus radiatus (formerly known as Elaphe radiata), an archetypal nonvenomous snake as sold in pet stores. This potent postsynaptic neurotoxin displays readily reversible, competitive antagonism at the nicotinic receptor. The toxin is homologous with, and phylogenetically rooted within, the three-finger toxins, previously thought unique to elapids, suggesting that this toxin family was recruited into the chemical arsenal of advanced snakes early in their evolutionary history. LC-MS analysis of venoms from most other advanced snake lineages revealed the widespread presence of components of the same molecular weight class, suggesting the ubiquity of three-finger toxins across advanced snakes, with the exclusion of Viperidae. These results support the role of venom as a key evolutionary innovation in the early diversification of advanced snakes and provide evidence that forces a fundamental rethink of the very concept of nonvenomous snake.

Keywords

Neurotoxin Venom Evolution Multi-gene Three finger Snake