Toxins 2013, 5(12), 2456-2487; doi:10.3390/toxins5122456
Article

Evolution Stings: The Origin and Diversification of Scorpion Toxin Peptide Scaffolds

1 CIMAR/CIIMAR, Centro Interdisciplinar de Investigação Marinha e Ambiental, Universidade do Porto, Rua dos Bragas, 177, 4050-123 Porto, Portugal 2 Departamento de Biologia, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre, 4169-007, Porto, Portugal 3 Venom Evolution Lab, School of Biological Sciences, The University of Queensland, St. Lucia, Queensland 4072, Australia 4 Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Queensland 4072, Australia 5 Department of Biochemistry and Molecular Biology, Centre for Comparative Genomics and Evolutionary Bioinformatics, Dalhousie University, Halifax, Nova Scotia, Canada These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 21 November 2013; in revised form: 9 December 2013 / Accepted: 9 December 2013 / Published: 13 December 2013
(This article belongs to the collection Evolution of Venom Systems)
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Abstract: The episodic nature of natural selection and the accumulation of extreme sequence divergence in venom-encoding genes over long periods of evolutionary time can obscure the signature of positive Darwinian selection. Recognition of the true biocomplexity is further hampered by the limited taxon selection, with easy to obtain or medically important species typically being the subject of intense venom research, relative to the actual taxonomical diversity in nature. This holds true for scorpions, which are one of the most ancient terrestrial venomous animal lineages. The family Buthidae that includes all the medically significant species has been intensely investigated around the globe, while almost completely ignoring the remaining non-buthid families. Australian scorpion lineages, for instance, have been completely neglected, with only a single scorpion species (Urodacus yaschenkoi) having its venom transcriptome sequenced. Hence, the lack of venom composition and toxin sequence information from an entire continent’s worth of scorpions has impeded our understanding of the molecular evolution of scorpion venom. The molecular origin, phylogenetic relationships and evolutionary histories of most scorpion toxin scaffolds remain enigmatic. In this study, we have sequenced venom gland transcriptomes of a wide taxonomical diversity of scorpions from Australia, including buthid and non-buthid representatives. Using state-of-art molecular evolutionary analyses, we show that a majority of CSα/β toxin scaffolds have experienced episodic influence of positive selection, while most non-CSα/β linear toxins evolve under the extreme influence of negative selection. For the first time, we have unraveled the molecular origin of the major scorpion toxin scaffolds, such as scorpion venom single von Willebrand factor C-domain peptides (SV-SVC), inhibitor cystine knot (ICK), disulphide-directed beta-hairpin (DDH), bradykinin potentiating peptides (BPP), linear non-disulphide bridged peptides and antimicrobial peptides (AMP). We have thus demonstrated that even neglected lineages of scorpions are a rich pool of novel biochemical components, which have evolved over millions of years to target specific ion channels in prey animals, and as a result, possess tremendous implications in therapeutics.
Keywords: adaptive evolution; scorpion venom arsenal; scorpion toxin scaffolds

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MDPI and ACS Style

Sunagar, K.; Undheim, E.A.B.; Chan, A.H.C.; Koludarov, I.; Muñoz-Gómez, S.A.; Antunes, A.; Fry, B.G. Evolution Stings: The Origin and Diversification of Scorpion Toxin Peptide Scaffolds. Toxins 2013, 5, 2456-2487.

AMA Style

Sunagar K, Undheim EAB, Chan AHC, Koludarov I, Muñoz-Gómez SA, Antunes A, Fry BG. Evolution Stings: The Origin and Diversification of Scorpion Toxin Peptide Scaffolds. Toxins. 2013; 5(12):2456-2487.

Chicago/Turabian Style

Sunagar, Kartik; Undheim, Eivind A.B.; Chan, Angelo H.C.; Koludarov, Ivan; Muñoz-Gómez, Sergio A.; Antunes, Agostinho; Fry, Bryan G. 2013. "Evolution Stings: The Origin and Diversification of Scorpion Toxin Peptide Scaffolds." Toxins 5, no. 12: 2456-2487.

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