Skip to main content

Viper Venom Botox: The Molecular Origin and Evolution of the Waglerin Peptides Used in Anti-Wrinkle Skin Cream

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, access via your institution.

Fig. 1
Fig. 2

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

    CAS  Article  Google Scholar 

  • 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

    CAS  Article  PubMed  Google Scholar 

  • 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

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • 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

    CAS  Article  PubMed  Google Scholar 

  • 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

    CAS  Article  PubMed  Google Scholar 

  • 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

    CAS  Article  PubMed  Google Scholar 

  • 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

    Google Scholar 

  • 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

    Google Scholar 

  • 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

    Google Scholar 

  • 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

    CAS  Article  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • 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

    CAS  Article  PubMed  Google Scholar 

  • 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

    CAS  Article  PubMed  Google Scholar 

  • 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

    Google Scholar 

  • 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

    CAS  Article  PubMed  Google Scholar 

  • 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

    Article  PubMed Central  Google Scholar 

Download references

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

Authors

Corresponding author

Correspondence to Bryan G. Fry.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00239-016-9764-6

Keywords

  • Bioactive Peptide
  • Skin Cream
  • Neurotoxic Peptide
  • Bicol
  • Benzylamide