Skip to main content

Advertisement

Log in

Molecular Evolution and Phylogeny of Elapid Snake Venom Three-Finger Toxins

  • Published:
Journal of Molecular Evolution Aims and scope Submit manuscript

Abstract

Animal venom components are of considerable interest to researchers across a wide variety of disciplines, including molecular biology, biochemistry, medicine, and evolutionary genetics. The three-finger family of snake venom peptides is a particularly interesting and biochemically complex group of venom peptides, because they are encoded by a large multigene family and display a diverse array of functional activities. In addition, understanding how this complex and highly varied multigene family evolved is an interesting question to researchers investigating the biochemical diversity of these peptides and their impact on human health. Therefore, the purpose of our study was to investigate the long-term evolutionary patterns exhibited by these snake venom toxins to understand the mechanisms by which they diversified into a large, biochemically diverse, multigene family. Our results show a much greater diversity of family members than was previously known, including a number of subfamilies that did not fall within any previously identified groups with characterized activities. In addition, we found that the long-term evolutionary processes that gave rise to the diversity of three-finger toxins are consistent with the birth-and-death model of multigene family evolution. It is anticipated that this “three-finger toxin toolkit” will prove to be useful in providing a clearer picture of the diversity of investigational ligands or potential therapeutics available within this important family.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9

Similar content being viewed by others

References

  1. F Afifiyan A Armugam CH Tan P Gopalakrishnakone K Jeyaseelan (1999) ArticleTitlePostsynaptic alpha-neurotoxin gene of the spitting cobra. Naja nafa sputatrix: Structure, organization, and phylogenetic analysis. Genome Res 9 IssueID3 259–266 Occurrence Handle1:CAS:528:DyaK1MXitVSitbo%3D Occurrence Handle10077532

    CAS  PubMed  Google Scholar 

  2. SD Aird GC Womble JR Yates 3rd PR Griffin (1999) ArticleTitlePrimary structure of γ-bungarotoxin, a new postsynaptic neurotoxin from venom of Bungarus multicinctus. Toxicon 37 IssueID4 609–625 Occurrence Handle10.1016/S0041-0101(98)00199-8 Occurrence Handle1:CAS:528:DyaK1MXht1ejsbk%3D Occurrence Handle10082161

    Article  CAS  PubMed  Google Scholar 

  3. S Antil D Servent A Ménez (1999) ArticleTitleVariability among the sites by which curaremimetic toxins bind to Torpedo acetylcholine receptor, as revealed by identification of the funcation residues of α-cobratoxin. J. Biol Chem 274 IssueID49 34851–34858 Occurrence Handle10.1074/jbc.274.49.34851 Occurrence Handle1:CAS:528:DyaK1MXnvFyrsbk%3D Occurrence Handle10574958

    Article  CAS  PubMed  Google Scholar 

  4. S Antil-Delbeke C Gaillard T Tamiya P-J Corringer J-P Changeux D Servent A Ménez (2000) ArticleTitleMolecular determinants by which a long chain toxin from snake venom interacts with the neuronal a7-nicotinic acetylcholine receptor. J Biol Chem 275 IssueID38 29594–29601 Occurrence Handle10.1074/jbc.M909746199 Occurrence Handle1:CAS:528:DC%2BD3cXmvFKjsbk%3D Occurrence Handle10852927

    Article  CAS  PubMed  Google Scholar 

  5. MT Assakura MFD Furtado FR Mandelbaum (1992) ArticleTitleBiochemical and biological differentiation of the venoms of the Lancehead vipers (Bothrops atrox, Bothrops asper, Bothrops marajoensis and Bothrops moojeni). Comp Biochem Physiol 102B 727–732 Occurrence Handle1:CAS:528:DyaK38XmtVKku7w%3D

    CAS  Google Scholar 

  6. WR Branch GV Haagner R Shine (1995) ArticleTitleIs there an ontogenetic shift in mamba diet? Taxonomic confusion and dietary records for black and green mambas (Dendroaspis: Elapidae). Herpetol Nat Hist 3 171–178

    Google Scholar 

  7. JM Carsi LT Potter (2000) ArticleTitlem1-toxin isoforms from the green mamba (Dendroaspis angusticeps) that selectively block m1 muscarinic receptors. Toxicon 38 187–198 Occurrence Handle10.1016/S0041-0101(99)00141-5 Occurrence Handle1:CAS:528:DyaK1MXns1Gqt70%3D Occurrence Handle10665800

    Article  CAS  PubMed  Google Scholar 

  8. JM Carsi HH Valentine LT Potter (1999) ArticleTitlem2-toxin: A selective ligand for m2 muscarinic receptors. Mol Pharmacol 56 933–937 Occurrence Handle1:CAS:528:DyaK1MXntV2mu70%3D Occurrence Handle10531397

    CAS  PubMed  Google Scholar 

  9. L Chang S Lin H Huang M Hsiao (1999) ArticleTitleGenetic organization of alpha-bungarotoxins from Bungarus multicinctus (Taiwan banded krait): Evidence showing that the production of α-bungarotoxin isotoxins is not derived from edited mRNAs. Nucleic Acids Res 27 IssueID20 3970–3975 Occurrence Handle10.1093/nar/27.20.3970 Occurrence Handle1:CAS:528:DyaK1MXnt1Ggtrw%3D Occurrence Handle10497260

    Article  CAS  PubMed  Google Scholar 

  10. JC Daltry W Wüster RS Thorpe (1996) ArticleTitleDiet and snake venom evolution. Nature 379 537–540 Occurrence Handle10.1038/379537a0 Occurrence Handle1:CAS:528:DyaK28XhtVWhsbo%3D Occurrence Handle8596631

    Article  CAS  PubMed  Google Scholar 

  11. MJ Dufton RC Hider (1991) The structure and pharmacology of elapid cytotoxins. AL Harvey (Eds) Snake toxins. Pergamon Press New York

    Google Scholar 

  12. T Endo N Tamiya (1987) ArticleTitleCurrent view on the structure-function relationship of postsynaptic neurotoxins from snake venoms. Pharmacol Ther 34 IssueID3 403–451 Occurrence Handle10.1016/0163-7258(87)90002-7 Occurrence Handle1:CAS:528:DyaL1cXhsleitg%3D%3D Occurrence Handle3324114

    Article  CAS  PubMed  Google Scholar 

  13. J Felsenstein (2001) PHYLIP (phylogeny inference package) version 36. Department of Genetics, University of Washington Seattle Occurrence Handle10.1080/106351501750435022 Occurrence Handle1:STN:280:DC%2BD38zntVOnuw%3D%3D Occurrence Handle12116645

    Book  CAS  PubMed  Google Scholar 

  14. TJ Fleming C Ohigin TR Malek (1993) ArticleTitleCharacterization of two novel Ly-6 genes. Protein sequence and potential structural similarity to a-bungarotoxin and other neurotoxins. J Immunol 150 5379–5390 Occurrence Handle1:CAS:528:DyaK3sXmt1eltro%3D Occurrence Handle8515066

    CAS  PubMed  Google Scholar 

  15. BG Fry JC Wickramaratna WC Hodgson PF Alewood RM Kini H Ho W Wüster (2002) ArticleTitleElectrospray liquid chromatography/mass spectrometry fingerprinting of Acanthophis (death adder) venoms: Taxonomic and toxinological implications. Rapid Commun Mass Spectrom 16 IssueID6 600–680 Occurrence Handle10.1002/rcm.613.abs Occurrence Handle1:CAS:528:DC%2BD38Xit1GjsLc%3D Occurrence Handle11870898

    Article  CAS  PubMed  Google Scholar 

  16. JL Glenn RC Straight MC Wolfe DL Hardy (1983) ArticleTitleGeographical variation in Crotalus scutulatus scutulatus (Mojave rattlesnake) venom properties. Toxicon 21 119–130 Occurrence Handle10.1016/0041-0101(83)90055-7 Occurrence Handle1:CAS:528:DyaL3sXhtlyksLY%3D Occurrence Handle6342208

    Article  CAS  PubMed  Google Scholar 

  17. N Gong A Armugam K Jeyaseelan (1999) ArticleTitlePostsynaptic short-chain neurotoxins from Pseudonaja textilis. cDNA cloning, expression and protein characterization. Eur J Biochem 265 IssueID3 982–989 Occurrence Handle10.1046/j.1432-1327.1999.00800.x Occurrence Handle1:CAS:528:DyaK1MXntFKrsrg%3D Occurrence Handle10518793

    Article  CAS  PubMed  Google Scholar 

  18. TP Gumley IFC McKenzie MS Sandrin (1995) ArticleTitleTissue expression, structure and function of the murine Ly-6 family of mole-cules. Immunol Cell Biol 73 277–296 Occurrence Handle1:CAS:528:DyaK2MXoslShsLo%3D Occurrence Handle7493764

    CAS  PubMed  Google Scholar 

  19. H Heatwole NS Poran (1995) ArticleTitleResistances of sympatric and allopatric eels to sea snake venoms. Copeia 1 136–147

    Google Scholar 

  20. JM Jiménez-Porras (1964) ArticleTitleIntraspecific variations in composition of venom of the jumping viper, Bothrops nummifera. Toxicon 2 187–195 Occurrence Handle10.1016/0041-0101(64)90021-2

    Article  Google Scholar 

  21. Jolkkonen M (1996) Muscarinic toxins from Dendroaspis (mamba) venoms. Peptides selective for subtypes of muscarinic acetylcholine receptors. Acta Universitatis Upsaliensis. Comprehensive summaries of Uppsala dissertations from the Faculty of Science and Techonology 183

  22. FJ Joubert N Taljaard (1978) ArticleTitleThe complete primary structure of toxin C from Dendroaspis polylepis polylepis (black mamba) venom. S Afr J Chem 31 107–110 Occurrence Handle1:CAS:528:DyaE1MXot1CisA%3D%3D

    CAS  Google Scholar 

  23. FJ Joubert N Taljaard (1979) ArticleTitleComplete primary structure of toxin CM-1C from Hemachatus haemachatus (Ringhals) venom. S Afr J Chem 32 73–77 Occurrence Handle1:CAS:528:DyaL3cXhslChtg%3D%3D

    CAS  Google Scholar 

  24. E Karlsson M Jokkonen E Mulugeta P Onali A Adem (2000) ArticleTitleSnake toxins with high selectivity for subtypes of muscarinic acetylcholine receptors. Biochimie 82 793–806 Occurrence Handle10.1016/S0300-9084(00)01176-7 Occurrence Handle1:CAS:528:DC%2BD3cXovFahsbs%3D Occurrence Handle11086210

    Article  CAS  PubMed  Google Scholar 

  25. JS Keogh (1998) ArticleTitleMolecular phylogeny of elapid snakes and a consideration of their biogeographic history. Biol J Linn Soc 63 177–203 Occurrence Handle10.1006/bijl.1997.0178

    Article  Google Scholar 

  26. JS Keogh R Shine S Donnellan (1998) ArticleTitlePhylogenetic relationships of terrestrial Australo-Papuan elapid snakes (Subfamily Hydrophiinae) based on cytochrome b and 16SrRNA sequences. Mol Phylogenet Evol 10 67–81 Occurrence Handle10.1006/mpev.1997.0471 Occurrence Handle1:CAS:528:DyaK1cXmtlOmtL0%3D Occurrence Handle9751918

    Article  CAS  PubMed  Google Scholar 

  27. RM Kini YM Chan (1999) ArticleTitleAccelerated evolution and molecular surface of venom phospholipase A(2) enzymes. J Mol Evol 48 125–132 Occurrence Handle1:CAS:528:DyaK1MXotVyrsw%3D%3D Occurrence Handle9929380

    CAS  PubMed  Google Scholar 

  28. D Kordis F Gubensek (2000) ArticleTitleAdaptive evolution of animal toxin multigene families. Gene 261 43–52 Occurrence Handle10.1016/S0378-1119(00)00490-X Occurrence Handle1:CAS:528:DC%2BD3MXmvF2msA%3D%3D Occurrence Handle11164036

    Article  CAS  PubMed  Google Scholar 

  29. TKS Kumar STK Pandian G Jayaraman HJ Peng C Yu (1999) ArticleTitleUnderstanding the structure, function and folding of cobra toxins. Proc Natl Sci Counc ROC(A) 23 IssueID1 1–19 Occurrence Handle1:CAS:528:DyaK1MXosVGqsg%3D%3D Occurrence Handle10551281

    CAS  PubMed  Google Scholar 

  30. A Ménez (1998) ArticleTitleFunctional architectures of animal toxins: A clue to drug design? Toxicon 36 IssueID11 1557–1572 Occurrence Handle10.1016/S0041-0101(98)00148-2 Occurrence Handle9792172

    Article  PubMed  Google Scholar 

  31. AM Moura-da-Silva MJ Paine MR Diniz RD Theakston JM Crampton (1995) ArticleTitleThe molecular cloning of a phospholipase A2 from Bothrops jararacussu snake venom: Evolution of venom group II phospholipase A2's may imply gene duplications. J Mol Evol 41 IssueID2 174–179 Occurrence Handle1:CAS:528:DyaK2MXntVSlt78%3D Occurrence Handle7666446

    CAS  PubMed  Google Scholar 

  32. K Nakashima I Nobuhisa M Deshimaru et al. (1995) ArticleTitleAccelerated evolution in the protein-coding regions is universal in crotalinae snake venom gland phospholipase A2 isozyme genes. Proc Natl Acad Sci USA 92 IssueID12 5605–5609 Occurrence Handle1:CAS:528:DyaK2MXmtFOgsbk%3D Occurrence Handle7777556

    CAS  PubMed  Google Scholar 

  33. M Nei X Gu T Sitnikova (1997) ArticleTitleEvolution by the birth-and-death process in multigene families of the vertebrate immune system. Proc Natl Acad Sci USA 94 IssueID15 7799–7806 Occurrence Handle1:CAS:528:DyaK2sXksl2nsbg%3D Occurrence Handle9223266

    CAS  PubMed  Google Scholar 

  34. S Nirthanan E Charpantier P Gopalakrishnakone MCE Gwee H-E Khoo L-S Cheah D Bertrand RM Kini (2002) ArticleTitleCandoxin, a novel toxin from Bungarus candidus, is a reversible antagonist of muscle (alphabetagammadelta) but a poorly reversible antagonist of neuronal alpha 7 nicotinic acetylcholine receptors. J Biol Chem 277 17811–17820 Occurrence Handle10.1074/jbc.M111152200 Occurrence Handle1:CAS:528:DC%2BD38XktVCnsbY%3D Occurrence Handle11884390

    Article  CAS  PubMed  Google Scholar 

  35. RD Page (2001) Gene Tree, version 130. University of Glasgow Glasgow Occurrence Handle11295509

    PubMed  Google Scholar 

  36. L Pillet O Tremeau F Ducancel P Drevet S Zinn-Justin S Pinkasfeld JC Boulain A Ménez (1993) ArticleTitleGenetic engineering of snake toxins. Role of invariant residues in the structural and functional properties of a curaremimetic toxin, as probed by site-directed mutagenesis. J Biol Chem 268 IssueID2 909–916 Occurrence Handle1:CAS:528:DyaK3sXltl2hsA%3D%3D Occurrence Handle8419369

    CAS  PubMed  Google Scholar 

  37. NS Poran RG Coss E Benjamini (1987) ArticleTitleResistance of California ground squirrels (Spermophilus beecheyi) to the venom of the northern Pacific rattlesnake (Crotalus viridis oreganus): A study of adaptive variation. Toxicon 25 IssueID7 767–777 Occurrence Handle10.1016/0041-0101(87)90127-9 Occurrence Handle1:CAS:528:DyaL2sXlslShurY%3D Occurrence Handle3672545

    Article  CAS  PubMed  Google Scholar 

  38. AP Rooney H Piontkivska M Nei (2002) ArticleTitleMolecular evolution of the nontandemly repeated genes of the histone 3 multigene family. Mol Biol Evol 19 IssueID1 68–75 Occurrence Handle1:CAS:528:DC%2BD38XhtFCisQ%3D%3D Occurrence Handle11752191

    CAS  PubMed  Google Scholar 

  39. N Saitou M Nei (1987) ArticleTitleThe neighbor-joining method: A new method for reconstructing phylogenetic trees. Mol Biol Evol 4 IssueID4 406–425 Occurrence Handle1:STN:280:BieC1cbgtVY%3D Occurrence Handle3447015

    CAS  PubMed  Google Scholar 

  40. JB Slowinski (1994) ArticleTitleA phylogenetic analysis of Bungarus (Elapidae) based on morphological characters. J Herpetol 28 440–446

    Google Scholar 

  41. JB Slowinski (1995) ArticleTitleA phylogenetic analysis of the New World coral snakes (Elapidae: Leptomicrurus, Micruroides, and Micrurus) based on allozymic and morphological characters. J Herpetol 29 325–338

    Google Scholar 

  42. JB Slowinski JS Keogh (2000) ArticleTitlePhylogenetic relationships of elapid snakes based on cytochrome b mtDNA sequences. Mol Phylogenet Evol 51 157–164 Occurrence Handle10.1006/mpev.1999.0725

    Article  Google Scholar 

  43. JB Slowinski A Knight AR Rooney (1997) ArticleTitleInferring species trees from gene trees: A phylogenetic analysis of the Elapidae (Serpentes) based on the amino acid sequences of venom proteins. Mol Phylogenet Evol 8 349–362 Occurrence Handle10.1006/mpev.1997.0434 Occurrence Handle1:CAS:528:DyaK1cXjtVeguw%3D%3D Occurrence Handle9417893

    Article  CAS  PubMed  Google Scholar 

  44. JB Slowinski J Boundy R Lawson (2001) ArticleTitleThe phylogenetic relationships of Asian coral snakes (Elapidae: Calliophis and Maticora) based on morphological and molecular characters. Herpetologica 57 233–245

    Google Scholar 

  45. R Stevens-Truss CL Hinman (1996) ArticleTitleChemical modification of methionines in a cobra venom cytotoxin differentiates between lytic and binding domains. Toxicol App Pharmacol 139 234–242 Occurrence Handle10.1006/taap.1996.0162 Occurrence Handle1:CAS:528:DyaK28XltVKns7Y%3D

    Article  CAS  Google Scholar 

  46. DS Swofford (2002) PAUP*: Phylogenetic analysis using parsimony (* and other methods), version 4.0b10 for Macintosh. Sinauer Associates Sunderland, MA

    Google Scholar 

  47. K Takahashi M Nei (2000) ArticleTitleEfficiencies of fast algorithms of phylogenetic inference under the criteria of maximum parsimony, minimum evolution, and maximum likelihood when a large number of sequences are used. Mol Biol Evol 17 1251–1258 Occurrence Handle1:CAS:528:DC%2BD3cXlvFCgs74%3D Occurrence Handle10908645

    CAS  PubMed  Google Scholar 

  48. M Takechi Y Tanaya K Ahayashi (1985) ArticleTitleAmino acid sequence of a cardiotoxin-like basic peptide (CLBP) with low cytotoxicity isolated from the venom of Formsan Cobra (Naja naja atra). Biochem Int 11 795–802 Occurrence Handle1:CAS:528:DyaL28XotlCmtw%3D%3D Occurrence Handle4091854

    CAS  PubMed  Google Scholar 

  49. JD Thompson TJ Gibson F Plewniak F Jeanmougin DG Higgins (1997) ArticleTitleThe CLUSTAL_X windows interface: Flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res 25 IssueID24 4876–4882 Occurrence Handle1:CAS:528:DyaK1cXntFyntQ%3D%3D Occurrence Handle9396791

    CAS  PubMed  Google Scholar 

  50. V Tsetlin (1999) ArticleTitleSnake venom alpha-neurotoxins and other ‘three-finger’ proteins. Eur J Biochem 264 IssueID2 281–286 Occurrence Handle10.1046/j.1432-1327.1999.00623.x Occurrence Handle1:CAS:528:DyaK1MXlvFWkur8%3D Occurrence Handle10491072

    Article  CAS  PubMed  Google Scholar 

  51. CC Viljoen DP Botes (1973) ArticleTitleSnake venom toxins. The purification and amino acid sequence of toxin F-VII from Dendroaspis angusticeps venom. J Biol Chem 248 4915–4919 Occurrence Handle1:CAS:528:DyaE3sXkslGiurw%3D Occurrence Handle4123919

    CAS  PubMed  Google Scholar 

  52. W Wüster CJ McCarthy (1996) Venomous snake systematics: Implications for snakebite treatment and toxinology. C Bon M Goyffon (Eds) Envenomings and their treatments. Fondation Mérieux Lyon 13–23

    Google Scholar 

  53. CC Yang LS Chang FS Wu (1991) ArticleTitleVenom constituents of Notechis scutatus scutatus (Australian tiger snake) from differing geographic regions. Toxicon 29 1337–1344 Occurrence Handle10.1016/0041-0101(91)90120-G Occurrence Handle1:CAS:528:DyaK38XksVahuro%3D Occurrence Handle1814009

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We dedicate this paper to the memory of our friend Dr. Joseph B. Slowinski, who died from snakebite in September of 2001 in Myanmar in the pursuit of new species of cobra. We are grateful for the financial assistance of the Australia and Pacific Science Foundation and the Melbourne Aquarium.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to B. G. Fry.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fry, B., Wüster, W., Kini, R. et al. Molecular Evolution and Phylogeny of Elapid Snake Venom Three-Finger Toxins . J Mol Evol 57, 110–129 (2003). https://doi.org/10.1007/s00239-003-2461-2

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00239-003-2461-2

Keywords

Navigation