Journal of Molecular Evolution

, Volume 68, Issue 4, pp 311–321 | Cite as

Tentacles of Venom: Toxic Protein Convergence in the Kingdom Animalia

  • B. G. FryEmail author
  • K. Roelants
  • J. A. Norman


The origin and evolution of venom in many animal orders remain controversial or almost entirely uninvestigated. Here we use cDNA studies of cephalopod posterior and anterior glands to reveal a single early origin of the associated secreted proteins. Protein types recoverd were CAP (CRISP, Antigen 5 [Ag5] and Pathogenesis-related [PR-1]), chitinase, peptidase S1, PLA2 (phospholipase A2), and six novel peptide types. CAP, chitinase, and PLA2 were each recovered from a single species (Hapalochlaena maculosa, Octopus kaurna, and Sepia latimanus, respectively), while peptidase S1 transcripts were found in large numbers in all three posterior gland libraries. In addition, peptidase S1 transcripts were recovered from the anterior gland of H. maculata. We compare their molecular evolution to that of related proteins found in invertebrate and vertebrate venoms, revealing striking similarities in the types of proteins selected for toxic mutation and thus shedding light on what makes a protein amenable for use as a toxin.


Venom Protein Phylogeny Cephalopod Convergence 



This work was funded by grants to B.G.F. from the Australian Academy of Science, Australian French Association for Science & Technology, Australia & Pacific Science Foundation, Australian Research Council (DP0665971 and DP0772814, to W.C.H. and J.A.N.), CASS Foundation, Ian Potter Foundation, International Human Frontiers Science Program Organisation, and the Netherlands Organisation for Scientific Research, University of Melbourne (Faculty of Medicine and Department of Biochemistry & Molecular Biology) and a Department of Innovation, Industry & Regional Development Victoria Fellowship. This work was also funded by an Australian Government Department of Education, Science & Training/EGIDE International Science Linkages grant to B.G.F and J.A.N. Accession numbers: GenBank accession numbers for sequences obtained in this study are EU790590–EU790615.


  1. Alape-Girón A, Persson B, Cederlund E, Flores-Díaz M, Gutiérrez JM, Thelestam M, Bergman T, Jörnvall H (1999) Elapid venom toxins: multiple recruitments of ancient scaffolds. Eur J Biochem 259(1–2):225–234PubMedCrossRefGoogle Scholar
  2. Amarant T, Burkhart W, LeVine H 3rd, Arocha-Pinango CL, Parikh I (1991) Isolation and complete amino acid sequence of two fibrinolytic proteinases from the toxic Saturnid caterpillar Lonomia achelous. Biochim Biophys Acta 1079(2):214–221PubMedGoogle Scholar
  3. Asgari S, Zhang G, Zareie R, Schmidt O (2003) A serine proteinase homolog venom protein from an endoparasitoid wasp inhibits melanization of the host hemolymph. Insect Biochem Mol Biol 33(10):1017–1024PubMedCrossRefGoogle Scholar
  4. Brown RL, Lynch LL, Haley TL, Arsanjani R (2003) Pseudechetoxin binds to the pore turret of cyclic nucleotide-gated ion channels. J Gen Physiol 122(6):749–760PubMedCrossRefGoogle Scholar
  5. Fang KS, Vitale M, Fehlner P, King TP (1998) cDNA cloning and primary structure of a white-face hornet venom allergen, antigen 5. Proc Natl Acad Sci USA 85(3):895–899CrossRefGoogle Scholar
  6. Froy O, Sagiv T, Poreh M, Urbach D, Zilberberg N, Gurevitz M (1999) Dynamic diversification from a putative common ancestor of scorpion toxins affecting sodium, potassium, and chloride channels. J Mol Evol 48(2):187–196PubMedCrossRefGoogle Scholar
  7. 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 15:403–420PubMedCrossRefGoogle Scholar
  8. Fry BG, Wuster W, Kini RM, Brusic V, Khan A, Venkataraman D, Rooney AP (2003) Molecular evolution of elapid snake venom three finger toxins. J Mol Evol 57(1):110–129PubMedCrossRefGoogle Scholar
  9. 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 Proteom 7(2):215–246CrossRefGoogle Scholar
  10. Fry BG, Roelants K, Champagne DE, Scheib H, Tyndall JDA, King GF, Nevalainen TJ, Norman JA, Lewis RJ, Norton RS, Renjifo C, de la Vega RCR (2009) The toxicogenomic multiverse: convergent recruitment of proteins into animal venoms. Annu Rev Genom Hum Genet (in press)Google Scholar
  11. Gennaro JF Jr, Lorincz AE, Brewster HB (1965) The anterior salivary gland of the octopus (Octopus vulgaris) and its mucous secretion. Ann NY Acad Sci 118(24):1021–1025PubMedCrossRefGoogle Scholar
  12. Kanda A, Iwakoshi-Ukena E, Takuwa-Kuroda K, Minakata H (2003) Isolation and characterization of novel tachykinins from the posterior salivary gland of the common octopus Octopus vulgaris. Peptides 24(1):35–43PubMedCrossRefGoogle Scholar
  13. Kanda A, Takuwa-Kuroda K, Aoyama M, Satake H (2007) A novel tachykinin-related peptide receptor of Octopus vulgaris–evolutionary aspects of invertebrate tachykinin and tachykinin-related peptide. FEBS J 274(9):2229–2239PubMedCrossRefGoogle Scholar
  14. Kita M, Nakamura Y, Okumura Y, Ohdachi SD, Oba Y, Yoshikuni M, Kido H, Uemura D (2004) Blarina toxin, a mammalian lethal venom from the short-tailed shrew Blarina brevicauda: isolation and characterization. Proc Natl Acad Sci USA 101(20):7542–7547PubMedCrossRefGoogle Scholar
  15. Krishnan A, Nair PN, Jones D (1994) Isolation, cloning, and characterization of new chitinase stored in active form in chitin-lined venom reservoir. J Biol Chem 269(33):20971–20976PubMedGoogle Scholar
  16. Milne TJ, Abbenante G, Tyndall JD, Halliday J, Lewis RJ (2003) Isolation and characterization of a cone snail protease with homology to CRISP proteins of the pathogenesis-related protein superfamily. J Biol Chem 278(33):31105–31110PubMedCrossRefGoogle Scholar
  17. Nevalainen TJ, Peuravuori HJ, Quinn RJ, Llewellyn LE, Benzie JA, Fenner PJ, Winkel KD (2004) Phospholipase A2 in cnidaria. Comp Biochem Physiol B Biochem Mol Biol 139(4):731–735PubMedCrossRefGoogle Scholar
  18. Nobile M, Magnelli V, Lagostena L, Mochca-Morales J, Possani LD, Prestipino G (1994) The toxin helothermine affects potassium currents in newborn rat cerebellar granule cells. J Membr Biol 139(1):49–55PubMedGoogle Scholar
  19. Norman N, Reid A (2000) A guide to squid, cuttlefish and octopuses of Australia. CSIRO Publishing, AustraliaGoogle Scholar
  20. Robertson A, Stirling D, Robillot C, Llewellyn L, Negri A (2004) First report of saxitoxin in octopi. Toxicon 44:765–771PubMedCrossRefGoogle Scholar
  21. Rodríguez de la Vega RC, Merino E, Becerril B, Possani LD (2003) Novel interactions between K+ channels and scorpion toxins. Trends Pharmacol Sci 24(5):222–227PubMedGoogle Scholar
  22. Strugnell J, Norman M, Jackson J, Drummond AJ, Cooper A (2005) Molecular phylogeny of coleoid cephalopods (Mollusca: Cephalopoda) using a multigene approach; the effect of data partitioning on resolving phylogenies in a Bayesian framework. Mol Phylogenet Evol 37(2):426–441PubMedCrossRefGoogle Scholar
  23. Sutherland SK, Lane WR (1969) Toxins and mode of envenomation of the common ringed or blue-banded octopus. Med J Aust 1(18):893–898PubMedGoogle Scholar
  24. Yotsu-Yamashita M, Mebs D, Flachsenberger W (2007) Distribution of tetrodotoxin in the body of the blue-ringed octopus (Hapalochlaena maculosa). Toxicon 49(3):410–412PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Department of Biochemistry and Molecular Biology, Venomics Research Laboratory, Bio21 Molecular Science and Biotechnology InstituteUniversity of MelbourneParkvilleAustralia
  2. 2.Biology DepartmentVrije Universiteit Brussel (VUB)BrusselsBelgium
  3. 3.Sciences DepartmentMuseum VictoriaMelbourneAustralia

Personalised recommendations