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Catch a tiger snake by its tail: Differential toxicity, co-factor dependence and antivenom efficacy in a procoagulant clade of Australian venomous snakes.

Abstract

A paradigm of venom research is adaptive evolution of toxins as part of a predator-prey chemical arms race. This study examined differential co-factor dependence, variations relative to dietary preference, and the impact upon relative neutralisation by antivenom of the procoagulant toxins in the venoms of a clade of Australian snakes. All genera were characterised by venoms rich in factor Xa which act upon endogenous prothrombin. Examination of toxin sequences revealed an extraordinary level of conservation, which indicates that adaptive evolution is not a feature of this toxin type. Consistent with this, the venoms did not display differences on the plasma of different taxa. Examination of the prothrombin target revealed endogenous blood proteins are under extreme negative selection pressure for diversification, this in turn puts a strong negative selection pressure upon the toxins as sequence diversification could result in a drift away from the target. Thus this study reveals that adaptive evolution is not a consistent feature in toxin evolution in cases where the target is under negative selection pressure for diversification. Consistent with this high level of toxin conservation, the antivenom showed extremely high-levels of cross-reactivity. There was however a strong statistical correlation between relative degree of phospholipid-dependence and clotting time, with the least dependent venoms producing faster clotting times than the other venoms even in the presence of phospholipid. The results of this study are not only of interest to evolutionary and ecological disciplines, but also have implications for clinical toxinology.

Authors+Show Affiliations

Venom Evolution Lab, School of Biological Sciences, University of Queensland, St Lucia, QLD, Australia.Department of Biosciences, College of Science, Swansea University, Swansea SA2, 8PP, UK.Venom Evolution Lab, School of Biological Sciences, University of Queensland, St Lucia, QLD, Australia; Australian Venom Research Unit, Department of Pharmacology and Therapeutics, University of Melbourne, Parkville, VIC 3010, Australia.Venom Evolution Lab, School of Biological Sciences, University of Queensland, St Lucia, QLD, Australia.Venom Evolution Lab, School of Biological Sciences, University of Queensland, St Lucia, QLD, Australia.Venom Evolution Lab, School of Biological Sciences, University of Queensland, St Lucia, QLD, Australia.Venom Supplies, Tanunda, SA, Australia.Venom Supplies, Tanunda, SA, Australia.Venom Evolution Lab, School of Biological Sciences, University of Queensland, St Lucia, QLD, Australia.Snakes Harmful & Harmless, 9 Birch Place, Stoneville, WA 6081, Australia.Fauna Vet Wildlife Veterinary Consultancy, Beerwah, QLD, Australia.Venom Evolution Lab, School of Biological Sciences, University of Queensland, St Lucia, QLD, Australia. Electronic address: bgfry@uq.edu.au.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28757215

Citation

Lister, Callum, et al. "Catch a Tiger Snake By Its Tail: Differential Toxicity, Co-factor Dependence and Antivenom Efficacy in a Procoagulant Clade of Australian Venomous Snakes." Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP, vol. 202, 2017, pp. 39-54.
Lister C, Arbuckle K, Jackson TNW, et al. Catch a tiger snake by its tail: Differential toxicity, co-factor dependence and antivenom efficacy in a procoagulant clade of Australian venomous snakes. Comp Biochem Physiol C Toxicol Pharmacol. 2017;202:39-54.
Lister, C., Arbuckle, K., Jackson, T. N. W., Debono, J., Zdenek, C. N., Dashevsky, D., Dunstan, N., Allen, L., Hay, C., Bush, B., Gillett, A., & Fry, B. G. (2017). Catch a tiger snake by its tail: Differential toxicity, co-factor dependence and antivenom efficacy in a procoagulant clade of Australian venomous snakes. Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP, 202, 39-54. https://doi.org/10.1016/j.cbpc.2017.07.005
Lister C, et al. Catch a Tiger Snake By Its Tail: Differential Toxicity, Co-factor Dependence and Antivenom Efficacy in a Procoagulant Clade of Australian Venomous Snakes. Comp Biochem Physiol C Toxicol Pharmacol. 2017;202:39-54. PubMed PMID: 28757215.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Catch a tiger snake by its tail: Differential toxicity, co-factor dependence and antivenom efficacy in a procoagulant clade of Australian venomous snakes. AU - Lister,Callum, AU - Arbuckle,Kevin, AU - Jackson,Timothy N W, AU - Debono,Jordan, AU - Zdenek,Christina N, AU - Dashevsky,Daniel, AU - Dunstan,Nathan, AU - Allen,Luke, AU - Hay,Chris, AU - Bush,Brian, AU - Gillett,Amber, AU - Fry,Bryan G, Y1 - 2017/07/27/ PY - 2017/06/06/received PY - 2017/07/07/revised PY - 2017/07/25/accepted PY - 2017/8/2/pubmed PY - 2018/1/10/medline PY - 2017/8/1/entrez KW - Adaptive evolution KW - Antivenom KW - Coagulopathy KW - Disseminated intravascular coagulation KW - Elapid KW - Toxin KW - Venom SP - 39 EP - 54 JF - Comparative biochemistry and physiology. Toxicology & pharmacology : CBP JO - Comp. Biochem. Physiol. C Toxicol. Pharmacol. VL - 202 N2 - A paradigm of venom research is adaptive evolution of toxins as part of a predator-prey chemical arms race. This study examined differential co-factor dependence, variations relative to dietary preference, and the impact upon relative neutralisation by antivenom of the procoagulant toxins in the venoms of a clade of Australian snakes. All genera were characterised by venoms rich in factor Xa which act upon endogenous prothrombin. Examination of toxin sequences revealed an extraordinary level of conservation, which indicates that adaptive evolution is not a feature of this toxin type. Consistent with this, the venoms did not display differences on the plasma of different taxa. Examination of the prothrombin target revealed endogenous blood proteins are under extreme negative selection pressure for diversification, this in turn puts a strong negative selection pressure upon the toxins as sequence diversification could result in a drift away from the target. Thus this study reveals that adaptive evolution is not a consistent feature in toxin evolution in cases where the target is under negative selection pressure for diversification. Consistent with this high level of toxin conservation, the antivenom showed extremely high-levels of cross-reactivity. There was however a strong statistical correlation between relative degree of phospholipid-dependence and clotting time, with the least dependent venoms producing faster clotting times than the other venoms even in the presence of phospholipid. The results of this study are not only of interest to evolutionary and ecological disciplines, but also have implications for clinical toxinology. SN - 1532-0456 UR - https://www.unboundmedicine.com/medline/citation/28757215/Catch_a_tiger_snake_by_its_tail:_Differential_toxicity_co_factor_dependence_and_antivenom_efficacy_in_a_procoagulant_clade_of_Australian_venomous_snakes_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1532-0456(17)30136-9 DB - PRIME DP - Unbound Medicine ER -