Medically important differences in snake venom composition are dictated by distinct postgenomic mechanisms

Casewell, N.R. and Wagstaff, S.C. and Wüster, W. and Cook, D.A.N. and Bolton, F.M.S. and King, S.I. and Plan, D. and Sanz. L., and Calvete, J.J. and Harrison, R.A. (2014) Medically important differences in snake venom composition are dictated by distinct postgenomic mechanisms. Proceedings of the National Academy of Sciences of the United States of America, 111 (25). pp. 9205-9210. DOI: 10.5061/dryad.1j292

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Variation in venom composition is a ubiquitous phenomenon in snakes and occurs both interspecifically and intraspecifically. Venom variation can have severe outcomes for snakebite victims by rendering the specific antibodies found in antivenoms ineffective against heterologous toxins found in different venoms. The rapid evolutionary expansion of different toxin-encoding gene families in different snake lineages is widely perceived as the main cause of venom variation. However, this view is simplistic and disregards the understudied influence that processes acting on gene transcription and translation may have on the production of the venom proteome. Here, we assess the venom composition of six related viperid snakes and compare interspecific changes in the number of toxin genes, their transcription in the venom gland, and their translation into proteins secreted in venom. Our results reveal that multiple levels of regulation are responsible for generating variation in venom composition between related snake species. We demonstrate that differential levels of toxin transcription, translation, and their posttranslational modification have a substantial impact upon the resulting venom protein mixture. Notably, these processes act to varying extents on different toxin paralogs found in different snakes and are therefore likely to be as important as ancestral gene duplication events for generating compositionally distinct venom proteomes. Our results suggest that these processes may also contribute to altering the toxicity of snake venoms, and we demonstrate how this variability can undermine the treatment of a neglected tropical disease, snakebite.

Item Type: Article
Subjects: Research Publications
Departments: College of Natural Sciences > School of Biological Sciences
Date Deposited: 18 Jul 2015 02:52
Last Modified: 20 Nov 2015 03:32
ISSN: 1091-6490
URI: http://e.bangor.ac.uk/id/eprint/4813
Identification Number: DOI: 10.5061/dryad.1j292
Publisher: Proceedings of the National Academy of Sciences
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