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

Casewell, Nicholas ORCID: https://orcid.org/0000-0002-8035-4719, Wagstaff, Simon ORCID: https://orcid.org/0000-0003-0577-5537, Wuster, W., Cook, Darren, Bolton, Fiona, King, Sarah, Pla, D., Sanz, L., Calvete, J. J. and Harrison, Robert (2014) 'Medically important differences in snake venom composition are dictated by distinct postgenomic mechanisms'. Proceedings of the National Academy of Sciences, Vol 111, Issue 25, pp. 9205-9210.

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Abstract

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:	QU Biochemistry > Genetics > QU 460 Genomics. Proteomics QW Microbiology and Immunology > Antigens and Antibodies. Toxins and Antitoxins > QW 630 Toxins. Antitoxins WD Disorders of Systemic, Metabolic or Environmental Origin, etc > Animal Poisons > WD 410 Reptiles
Faculty: Department:	Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI):	https://doi.org/10.1073/pnas.1405484111
Depositing User:	Lynn Roberts-Maloney
Date Deposited:	07 Apr 2015 13:29
Last Modified:	17 Sep 2019 13:33
URI:	https://archive.lstmed.ac.uk/id/eprint/5062

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