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

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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.

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Acknowledgements

We would like to thank Dr. Paolo Martelli, Sheik Fadil Ryan Ramjan, and Timothy Jackson for all their help. We would also like to thank the Singapore Zoo for the provision of space and facilities for our snake collection. We are grateful for the financial assistance of the Australia and Pacific Science Foundation, Biomedical Medical Research Council (Singapore), and the Monash University Small Grant Scheme.

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Authors and Affiliations

  1. Department of Biological Sciences, Faculty of Science, National University of Singapore, 119260 , Singapore

    Bryan G. Fry & R. Manjunatha Kini

  2. Australian Venom Research Unit, Department of Pharmacology, University of Melbourne, Parkville, Victoria 3010, Australia

    Bryan G. Fry

  3. Monash Venom Group, Department of Pharmacology, Monash University, Victoria 3800, Australia

    Natalie G. Lumsden, Janith C. Wickramaratna & Wayne C. Hodgson

  4. School of Biological Sciences, University of Wales, Bangor, LL57 2UW, Wales, United Kingdom

    Wolfgang Wüster

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  1. Bryan G. Fry
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  2. Natalie G. Lumsden
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  3. Wolfgang Wüster
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  4. Janith C. Wickramaratna
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  5. Wayne C. Hodgson
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  6. R. Manjunatha Kini
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Correspondence to Bryan G. Fry.

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Fry, B.G., Lumsden, N.G., Wüster, W. et al. Isolation of a Neurotoxin (α-colubritoxin) from a Nonvenomous Colubrid: Evidence for Early Origin of Venom in Snakes . J Mol Evol 57, 446–452 (2003). https://doi.org/10.1007/s00239-003-2497-3

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  • DOI: https://doi.org/10.1007/s00239-003-2497-3

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