Abstract
The molecular origin of waglerin peptides has remained enigmatic despite their industrial application in skin cream products to paralyse facial muscles and thus reduce the incidence of wrinkles. Here we show that these neurotoxic peptides are the result of de novo evolution within the prepro region of the C-type natriuretic peptide gene in Tropidolaemus venoms, at a site distinct from the domain encoding for the natriuretic peptide. It is the same region that yielded the azemiopsin peptides from Azemiops feae, indicative of a close relationship of this toxin gene between these two genera. The precursor region for the molecular evolution is a biodiversity hotspot that has yielded other novel bioactive peptides with novel activities. We detail the diversity of components in this and other species in order to explore what characteristics enable it to be such a biodiscovery treasure trove. The unusual function of Tropidolaemus venoms may have been selected for due to evolutionary pressures brought about by a high likelihood of prey escape.
This is a preview of subscription content, log in via an institution to check access.
References
Balaev AN, Okhmanovich KA, Osipov VN (2014) A shortened, protecting group free, synthesis of the anti-wrinkle venom analogue Syn-Ake® exploiting an optimized Hofmann-type rearrangement. Tetrahedron Lett 55:5745
Brust A, Sunagar K, Undheim EA, Vetter I, Yang DC, Casewell NR, Jackson TN, Koludarov I, Alewood PF, Hodgson WC, Lewis RJ, King GF, Antunes A, Hendrikx I, Fry BG (2013) Differential evolution and neofunctionalization of snake venom metalloprotease domains. Mol Cell Proteomics 12:651
Fry BG (2005) From genome to “venome”: molecular origin and evolution of the snake venom proteome inferred from phylogenetic analysis of toxin sequences and related body proteins. Genome Res 15:403
Fry BG, Wuster W, Ramjan SFR, Jackson T, Martelli P, Kini RM (2003) Analysis of Colubroidea snake venoms by liquid chromatography with mass spectrometry: evolutionary and toxinological implications. Rapid Commun Mass Spectrom 17:2047
Fry BG, Scheib H, van der Weerd L, Young B, McNaughtan J, Ramjan SF, Vidal N, Poelmann RE, Norman JA (2008) Evolution of an arsenal: structural and functional diversification of the venom system in the advanced snakes (Caenophidia). Mol Cell Proteomics 7:215
Fry BG, Roelants K, Winter K, Hodgson WC, Griesman L, Kwok HF, Scanlon D, Karas J, Shaw C, Wong L, Norman JA (2010) Novel venom proteins produced by differential domain-expression strategies in beaded lizards and gila monsters (genus Heloderma). Mol Biol Evol 27:395
Fry BG, Richards R, Earl S, Cousin X, Jackson TNW, Weise C, Sunagar K (2015a) Lesser-known or putative reptile toxins. In: Fry BG (ed) Venomous reptiles and their toxins. Oxford University Press, New York, pp 364–407
Fry BG, Jackson TNW, Takacs Z, Reeks T, Sunagar K (2015b) C-type natriuretic peptides. In: Fry BG (ed) Venomous reptiles and their toxins: evolution, pathophysiology and biodiscovery. Oxford University Press, New York, pp 318–326
Fry BG, Sunagar K, Jackson TNW, Reeks T, Kwok HF (2015c) B-type natriuretic peptides. In: Fry BG (ed) Venomous reptiles and their toxins: evolution, pathophysiology and biodiscovery. Oxford University Press, New York
Lin WW, Smith LA, Lee CY (1995) A study on the cause of death due to waglerin-I, a toxin from Trimeresurus wagleri. Toxicon 33:111
McArdle JJ, Lentz TL, Witzemann V, Schwarz H, Weinstein SA, Schmidt JJ (1999) Waglerin-1 selectively blocks the epsilon form of the muscle nicotinic acetylcholine receptor. J Pharmacol Exp Ther 289:543
Schmidt JJ, Weinstein SA (1995) Structure-function studies of waglerin I, a lethal peptide from the venom of Wagler’s pit viper, Trimeresurus wagleri. Toxicon 33:1043
Schmidt JJ, Weinstein SA, Smith LA (1992) Molecular properties and structure-function relationships of lethal peptides from venom of Wagler’s pit viper, Trimeresurus wagleri. Toxicon 30:1027
Trookman NS, Rizer RL, Ford R, Ho E, Gotz V (2009) Immediate and long-term clinical benefits of a topical treatment for facial lines and wrinkles. J Clin Aesthetic Dermatol 2:38
Utkin YN, Weise Ch, Hoang NA, Kasheverov IE, Starkov VG, Tsetlin VI (2012a) The new peptide from the Fea’s viper Azemiops feae venom interacts with nicotinic acetylcholine receptors. Dokl Biochem Biophys 442:33
Utkin YN, Weise C, Kasheverov IE, Andreeva TV, Kryukova EV, Zhmak MN, Starkov VG, Hoang NA, Bertrand D, Ramerstorfer J, Sieghart W, Thompson AJ, Lummis SC, Tsetlin VI (2012b) Azemiopsin from Azemiops feae viper venom, a novel polypeptide ligand of nicotinic acetylcholine receptor. J Biol Chem 287(32):27079
Yang DC, Deuis JR, Dashevsky D, Dobson J, Jackson TNW, Brust A, Xie B, Koludarov I, Debono J, Hendrikx I, Hodgson WC, Josh P, Nouwens A, Baillie GJ, Bruxner JC, Alewood PF, Lim KKP, Frank N, Vetter I, Fry BG (2016) The Snake with the Scorpion’s sting: novel three-finger toxin sodium channel activators from the venom of the long-glanded blue coral snake (Calliophis bivirgatus). Toxins 8:303. doi:10.3390/toxins8100303
Acknowledgements
BGF was funded by an Australian Research Council and by the University of Queensland. JD was funded by an Australian Postgraduate Award.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Debono, J., Xie, B., Violette, A. et al. Viper Venom Botox: The Molecular Origin and Evolution of the Waglerin Peptides Used in Anti-Wrinkle Skin Cream. J Mol Evol 84, 8–11 (2017). https://doi.org/10.1007/s00239-016-9764-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00239-016-9764-6