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Deadly Innovations: Unraveling the Molecular Evolution of Animal Venoms

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Book cover Venom Genomics and Proteomics

Part of the book series: Toxinology ((TOXI))

Abstract

Understanding the nature and strength of natural selection that influences the evolution of genes is one of the major aspects of modern evolutionary biological studies. Animal venoms are complex cocktails of biologically active compounds that are secreted in a specialized gland and actively delivered to the target animal through the infliction of a wound. The injected molecules cause a disruption in the normal physiological and biochemical processes of the victim, typically in order to facilitate the feeding or defense of the venomous animal. Venom components have been theorized to have originated from the physiological protein-encoding genes. The molecular evolution of venom has been suggested to be influenced by numerous ecological and evolutionary factors, such as diet, prey distribution, predator pressure, ontogenetic shifts, and the gender of the animal. Because of the medical importance of venom proteins, many of which are amenable for therapeutic or diagnostic development as pharmaceutical compounds while others cause catastrophic pathology in envenomed humans, a comprehensive understanding of the origin of venom proteins and the evolutionary forces shaping their biodiversity is essential to unravel the complete biodiscovery potential of this nature’s most biochemically complex cocktail. The current state of knowledge regarding venom evolution, as well as the potential relevance of this topic in the advancement of the biomedical field, has been reviewed here.

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References

  • Ambros V. The functions of animal micrornas. Nature. 2004;431:350–5.

    Article  CAS  PubMed  Google Scholar 

  • Andrade D, Abe A. Relationship of venom ontogeny and diet in Bothrops. Herpetologica. 1999;55:200–4.

    Google Scholar 

  • Barlow A, Pook CE, Harrison RA, Wuster W. Coevolution of diet and prey-specific venom activity supports the role of selection in snake venom evolution. Proc Biol Sci. 2009;276:2443–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Benkhadir K, Kharrat R, Cestele S, Mosbah A, Rochat H, El Ayeb M, Karoui H. Molecular cloning and functional expression of the alpha-scorpion toxin Botiii: pivotal role of the c-terminal region for its interaction with voltage-dependent sodium channels. Peptides. 2004;25:151–61.

    Article  CAS  PubMed  Google Scholar 

  • Betz SF. Disulfide bonds and the stability of globular proteins. Protein Sci. 1993;2:1551–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Binford GJ. An analysis of geographic and intersexual chemical variation in venoms of the spider Tegenaria agrestis (Agelenidae). Toxicon. 2001;39:955–68.

    Article  CAS  PubMed  Google Scholar 

  • Black DL. Mechanisms of alternative pre-messenger rna splicing. Annu Rev Biochem. 2003;72:291–336.

    Article  CAS  PubMed  Google Scholar 

  • Boldrini-Franca J, Correa-Netto C, Silva MM, Rodrigues RS, De La Torre P, Perez A, Soares AM, Zingali RB, Nogueira RA, Rodrigues VM, et al. Snake venomics and antivenomics of Crotalus durissus subspecies from Brazil: assessment of geographic variation and its implication on snakebite management. J Proteomics. 2010;73:1758–76.

    Article  CAS  PubMed  Google Scholar 

  • Brust A, Sunagar K, Undheim EA, Vetter I, Yang DC, Casewell NR, Jackson TN, Koludarov I, Alewood PF, Hodgson WC, et al. Differential evolution and neofunctionalization of snake venom metalloprotease domains. Mol Cell Proteomics. 2013;12:651–63.

    Article  CAS  PubMed  Google Scholar 

  • Carlini CR, Grossi-de-Sa MF. Plant toxic proteins with insecticidal properties. A review on their potentialities as bioinsecticides. Toxicon. 2002;40:1515–39.

    Article  CAS  PubMed  Google Scholar 

  • Chu NS. Contribution of a snake venom toxin to myasthenia gravis: the discovery of alpha-bungarotoxin in Taiwan. J Hist Neurosci. 2005;14:138–48.

    Article  PubMed  Google Scholar 

  • Condrea E. Hemolytic disorders associated with a primary red cell membrane defect. Experientia. 1976;32:537–42.

    Article  CAS  PubMed  Google Scholar 

  • Conticello SG, Pilpel Y, Glusman G, Fainzilber M. Position-specific codon conservation in hypervariable gene families. Trends Genet. 2000;16:57–9.

    Article  CAS  PubMed  Google Scholar 

  • Conticello SG, Gilad Y, Avidan N, Ben-Asher E, Levy Z, Fainzilber M. Mechanisms for evolving hypervariability: the case of conopeptides. Mol Biol Evol. 2001;18:120–31.

    Article  CAS  PubMed  Google Scholar 

  • Cousin X, Bon S, Massoulie J, Bon C. Identification of a novel type of alternatively spliced exon from the acetylcholinesterase gene of bungarus fasciatus. Molecular forms of acetylcholinesterase in the snake liver and muscle. J Biol Chem. 1998;273:9812–20.

    Article  CAS  PubMed  Google Scholar 

  • Daltry JC, Wuster W, Thorpe RS. Diet and snake venom evolution. Nature. 1996;379:537–40.

    Article  CAS  PubMed  Google Scholar 

  • Dawkar VV, Chikate YR, Lomate PR, Dholakia BB, Gupta VS, Giri AP. Molecular insights into resistance mechanisms of lepidopteran insect pests against toxicants. J Proteome Res. 2013;12:4727–37.

    Article  CAS  PubMed  Google Scholar 

  • Delpietro HA, Russo RG. Acquired resistance to saliva anticoagulants by prey previously fed upon by vampire bats (Desmodus rotundus): evidence for immune response. J Mammal. 2009;90:1132–8.

    Article  Google Scholar 

  • Doley R, Kini RM. Protein complexes in snake venom. Cell Mol Life Sci. 2009;66:2851–71.

    Article  CAS  PubMed  Google Scholar 

  • Doley R, Mackessy SP, Kini RM. Role of accelerated segment switch in exons to alter targeting (asset) in the molecular evolution of snake venom proteins. BMC Evol Biol. 2009;9:146.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Duda Jr TF, Palumbi SR. Molecular genetics of ecological diversification: duplication and rapid evolution of toxin genes of the venomous gastropod conus. Proc Natl Acad Sci U S A. 1999;96:6820–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Durban J, Juarez P, Angulo Y, Lomonte B, Flores-Diaz M, Alape-Giron A, Sasa M, Sanz L, Gutierrez JM, Dopazo J, et al. Profiling the venom gland transcriptomes of Costa Rican snakes by 454 pyrosequencing. BMC Genomics. 2011;12:259.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Durban J, Perez A, Sanz L, Gomez A, Bonilla F, Rodriguez S, Chacon D, Sasa M, Angulo Y, Gutierrez J, et al. Integrated “omics” profiling indicates that mirnas are modulators of the ontogenetic venom composition shift in the Central American rattlesnake, Crotalus simus simus. BMC Genomics. 2013;14:234.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dutertre S, Jin AH, Vetter I, Hamilton B, Sunagar K, Lavergne V, Dutertre V, Fry BG, Antunes A, Venter DJ, et al. Evolution of separate predation- and defence-evoked venoms in carnivorous cone snails. Nat Commun. 2014;5:3521.

    PubMed  PubMed Central  Google Scholar 

  • Earl ST, Birrell GW, Wallis TP, St Pierre LD, Masci PP, de Jersey J, Gorman JJ, Lavin MF. Post-translational modification accounts for the presence of varied forms of nerve growth factor in Australian elapid snake venoms. Proteomics. 2006;6:6554–65.

    Article  CAS  PubMed  Google Scholar 

  • Eickbush TH, Eickbush DG. Finely orchestrated movements: evolution of the ribosomal rna genes. Genetics. 2007;175:477–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Elbein AD. Glycosidase inhibitors: inhibitors of n-linked oligosaccharide processing. FASEB J. 1991;5:3055–63.

    CAS  PubMed  Google Scholar 

  • Estrada-Gomez S, Cupitra NI, Arango WM, Munoz LJ. Intraspecific variation of centruroides edwardsii venom from two regions of Colombia. Toxins. 2014;6:2082–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eyre-Walker A. 2006. The genomic rate of adaptive evolution. Trends Ecol Evol 21:569–575.

    Google Scholar 

  • Fox RC, Scott CS. First evidence of a venom delivery apparatus in extinct mammals. Nature. 2005;435:1091–3.

    Article  CAS  PubMed  Google Scholar 

  • Frade JM, Barde YA. Genetic evidence for cell death mediated by nerve growth factor and the neurotrophin receptor p75 in the developing mouse retina and spinal cord. Development. 1999;126:683–90.

    CAS  PubMed  Google Scholar 

  • Fry BG. 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. 2005;15:403–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fry BG, Wickramaratna JC, Hodgson WC, Alewood PF, Kini RM, Ho H, Wuster W. Electrospray liquid chromatography/mass spectrometry fingerprinting of acanthophis (death adder) venoms: taxonomic and toxinological implications. Rapid Commun Mass Spectrom. 2002;16:600–8.

    Article  CAS  PubMed  Google Scholar 

  • Fry BG, Roelants K, Champagne DE, Scheib H, Tyndall JD, King GF, Nevalainen TJ, Norman JA, Lewis RJ, Norton RS, et al. The toxicogenomic multiverse: convergent recruitment of proteins into animal venoms. Annu Rev Genomics Hum Genet. 2009a;10:483–511.

    Article  CAS  PubMed  Google Scholar 

  • Fry BG, Vidal N, van der Weerd L, Kochva E, Renjifo C. Evolution and diversification of the toxicofera reptile venom system. J Proteomics. 2009b;72:127–36.

    Article  CAS  PubMed  Google Scholar 

  • Gibbs HL, Sanz L, Chiucchi JE, Farrell TM, Calvete JJ. Proteomic analysis of ontogenetic and diet-related changes in venom composition of juvenile and adult dusky pigmy rattlesnakes (Sistrurus miliarius barbouri). J Proteomics. 2011;74:2169–79.

    Article  CAS  PubMed  Google Scholar 

  • Gibbs HL, Sanz L, Sovic MG, Calvete JJ. Phylogeny-based comparative analysis of venom proteome variation in a clade of rattlesnakes (Sistrurus sp.). PLoS One. 2013;8:e67220.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Goldman N, Yang Z. A codon-based model of nucleotide substitution for protein-coding DNA sequences. Mol Biol Evol. 1994;11:725–36.

    CAS  PubMed  Google Scholar 

  • Gong N, Armugam A, Jeyaseelan K. Molecular cloning, characterization and evolution of the gene encoding a new group of short-chain alpha-neurotoxins in an Australian elapid, Pseudonaja textilis. FEBS Lett. 2000;473:303–10.

    Article  CAS  PubMed  Google Scholar 

  • Gong E, Martin LD, Burnham DA, Falk AR. The birdlike raptor sinornithosaurus was venomous. Proc Natl Acad Sci U S A. 2010;107:766–8.

    Article  CAS  PubMed  Google Scholar 

  • Gowda DC, Jackson CM, Hensley P, Davidson EA. Factor x-activating glycoprotein of Russell’s viper venom. Polypeptide composition and characterization of the carbohydrate moieties. J Biol Chem. 1994;269:10644–50.

    CAS  PubMed  Google Scholar 

  • Gregory-Dwyer VM, Egen NB, Bosisio AB, Righetti PG, Russell FE. An isoelectric focusing study of seasonal variation in rattlesnake venom proteins. Toxicon. 1986;24:995–1000.

    Article  CAS  PubMed  Google Scholar 

  • Guercio RA, Shevchenko A, Shevchenko A, Lopez-Lozano JL, Paba J, Sousa MV, Ricart CA. Ontogenetic variations in the venom proteome of the Amazonian snake Bothrops atrox. Proteome Sci. 2006;4:11.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hargreaves AD, Swain MT, Hegarty MJ, Logan DW, Mulley JF. Restriction and recruitment-gene duplication and the origin and evolution of snake venom toxins. Genome Biol Evol. 2014;6:2088–95.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Herzig V, Wood DL, Newell F, Chaumeil PA, Kaas Q, Binford GJ, Nicholson GM, Gorse D, King GF. Arachnoserver 2.0, an updated online resource for spider toxin sequences and structures. Nucleic Acids Res. 2011;39:D653–7.

    Article  CAS  PubMed  Google Scholar 

  • Honma T, Hasegawa Y, Ishida M, Nagai H, Nagashima Y, Shiomi K. Isolation and molecular cloning of novel peptide toxins from the sea anemone antheopsis maculata. Toxicon. 2005;45:33–41.

    Article  CAS  PubMed  Google Scholar 

  • Hughes JP, Rees S, Kalindjian SB, Philpott KL. Principles of early drug discovery. Br J Pharmacol. 2011;162:1239–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Inceoglu B, Lango J, Jing J, Chen L, Doymaz F, Pessah IN, Hammock BD. One scorpion, two venoms: prevenom of Parabuthus transvaalicus acts as an alternative type of venom with distinct mechanism of action. Proc Natl Acad Sci U S A. 2003;100:922–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Johnson EK, Kardong KV, Ownby CL. Observations on white and yellow venoms from an individual southern pacific rattlesnake (Crotalus viridis helleri). Toxicon. 1987;25:1169–80.

    Article  CAS  PubMed  Google Scholar 

  • Johnson JH, Bloomquist JR, Krapcho KJ, Kral Jr RM, Trovato R, Eppler KG, Morgan TK, DelMar EG. Novel insecticidal peptides from Tegenaria agrestis spider venom may have a direct effect on the insect central nervous system. Arch Insect Biochem Physiol. 1998;38:19–31.

    Article  CAS  PubMed  Google Scholar 

  • Kashnikova OV. Poisonousness of the scorpion buthus eupeus. Izv Akad Nauk Kazakh Ssr Ser Biol. 1979;17:30–5.

    Google Scholar 

  • Kasturiratne A, Wickremasinghe AR, de Silva N, Gunawardena NK, Pathmeswaran A, Premaratna R, Savioli L, Lalloo DG, de Silva HJ. The global burden of snakebite: a literature analysis and modelling based on regional estimates of envenoming and deaths. PLoS Med. 2008;5:e218.

    Article  PubMed  PubMed Central  Google Scholar 

  • King GF, Hardy MC. Spider-venom peptides: structure, pharmacology, and potential for control of insect pests. Annu Rev Entomol. 2013;58:475–96.

    Article  CAS  PubMed  Google Scholar 

  • Kini RM, Chan YM. Accelerated evolution and molecular surface of venom phospholipase a2 enzymes. J Mol Evol. 1999;48:125–32.

    Article  CAS  PubMed  Google Scholar 

  • Kochva, E. Oral Glands of the Reptilia In: Biology of the Reptilia, C. Gans and K.A. Gans (Eds.), Academic Press, London and New York, 1978;43–161.

    Google Scholar 

  • Kochva E. The origin of snakes and evolution of the venom apparatus. Toxicon. 1987;25:65–106.

    Article  CAS  PubMed  Google Scholar 

  • Kochva E, Nakar O, Ovadia M. Venom toxins: plausible evolution from digestive enzymes. Am Zool. 1983;23:427–30.

    Article  CAS  Google Scholar 

  • Kozminsky-Atias A, Zilberberg N. Molding the business end of neurotoxins by diversifying evolution. FASEB J. 2012;26:576–86.

    Article  CAS  PubMed  Google Scholar 

  • Low DH, Sunagar K, Undheim EA, Ali SA, Alagon AC, Ruder T, Jackson TN, Pineda Gonzalez S, King GF, Jones A, et al. Dracula’s children: molecular evolution of vampire bat venom. J Proteomics. 2013;89:95–111.

    Article  CAS  PubMed  Google Scholar 

  • Mackessy SP. Venom ontogeny in the pacific rattlesnakes, Crotalus viridis helleri and C. viridis oreganus. Copeia. 1988;1988:92–101.

    Article  Google Scholar 

  • Mackessy SP. Evolutionary trends in venom composition in the western rattlesnakes (Crotalus viridis sensu lato): toxicity vs. tenderizers. Toxicon. 2010;55:1463–74.

    Article  CAS  PubMed  Google Scholar 

  • Mackessy SP, Sixberry NM, Heyborne WH, Fritts T. Venom of the brown treesnake, Boiga irregularis: ontogenetic shifts and taxa-specific toxicity. Toxicon. 2006;47:537–48.

    Article  CAS  PubMed  Google Scholar 

  • Maor-Shoshani A, Reuven NB, Tomer G, Livneh Z. Highly mutagenic replication by DNA polymerase v (umuc) provides a mechanistic basis for sos untargeted mutagenesis. Proc Natl Acad Sci U S A. 2000;97:565–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marques G, Musacchio M, Shimell MJ, Wunnenberg-Stapleton K, Cho KW, O’Connor MB. Production of a dpp activity gradient in the early drosophila embryo through the opposing actions of the sog and tld proteins. Cell. 1997;91:417–26.

    Article  CAS  PubMed  Google Scholar 

  • Meng XY, Zhang HX, Mezei M, Cui M. Molecular docking: a powerful approach for structure-based drug discovery. Curr Comput Aided Drug Des. 2011;7:146–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moran Y, Kahn R, Cohen L, Gur M, Karbat I, Gordon D, Gurevitz M. Molecular analysis of the sea anemone toxin av3 reveals selectivity to insects and demonstrates the heterogeneity of receptor site-3 on voltage-gated na + channels. Biochem J. 2007;406:41–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moran Y, Weinberger H, Sullivan JC, Reitzel AM, Finnerty JR, Gurevitz M. Concerted evolution of sea anemone neurotoxin genes is revealed through analysis of the nematostella vectensis genome. Mol Biol Evol. 2008a;25:737–47.

    Article  CAS  PubMed  Google Scholar 

  • Moran Y, Weinberger H, Reitzel AM, Sullivan JC, Kahn R, Gordon D, Finnerty JR, Gurevitz M. Intron retention as a posttranscriptional regulatory mechanism of neurotoxin expression at early life stages of the starlet anemone nematostella vectensis. J Mol Biol. 2008b;380:437–43.

    Article  CAS  PubMed  Google Scholar 

  • Moran Y, Gordon D, Gurevitz M. Sea anemone toxins affecting voltage-gated sodium channels – molecular and evolutionary features. Toxicon. 2009a;54:1089–101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moran Y, Weinberger H, Lazarus N, Gur M, Kahn R, Gordon D, Gurevitz M. Fusion and retrotransposition events in the evolution of the sea anemone Anemonia viridis neurotoxin genes. J Mol Evol. 2009b;69:115–24.

    Article  CAS  PubMed  Google Scholar 

  • Moran Y, Genikhovich G, Gordon D, Wienkoop S, Zenkert C, Ozbek S, Technau U, Gurevitz M. Neurotoxin localization to ectodermal gland cells uncovers an alternative mechanism of venom delivery in sea anemones. Proc Biol Sci. 2012;279:1351–8.

    Article  CAS  PubMed  Google Scholar 

  • Moran Y, Praher D, Schlesinger A, Ayalon A, Tal Y, Technau U. Analysis of soluble protein contents from the nematocysts of a model sea anemone sheds light on venom evolution. Marine Biotechnol. 2013;15:329–39.

    Article  CAS  Google Scholar 

  • Murrell B, Wertheim JO, Moola S, Weighill T, Scheffler K, Kosakovsky Pond SL. Detecting individual sites subject to episodic diversifying selection. PLoS Genet. 2012;8:e1002764.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Murrell B, Moola S, Mabona A, Weighill T, Sheward D, Kosakovsky Pond SL, Scheffler K. Fubar: a fast, unconstrained bayesian approximation for inferring selection. Mol Biol Evol. 2013;30:1196–205.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nei M, Gu X, Sitnikova T. Evolution by the birth-and-death process in multigene families of the vertebrate immune system. Proc Natl Acad Sci U S A. 1997;94:7799–806.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nirthanan S, Gwee MC. Three-finger alpha-neurotoxins and the nicotinic acetylcholine receptor, forty years on. J Pharmacol Sci. 2004;94:1–17.

    Article  CAS  PubMed  Google Scholar 

  • Nisani Z, Boskovic DS, Dunbar SG, Kelln W, Hayes WK. Investigating the chemical profile of regenerated scorpion (Parabuthus transvaalicus) venom in relation to metabolic cost and toxicity. Toxicon. 2012;60:315–23.

    Article  CAS  PubMed  Google Scholar 

  • Norton RS, Pallaghy PK. The cystine knot structure of ion channel toxins and related polypeptides. Toxicon. 1998;36:1573–83.

    Article  CAS  PubMed  Google Scholar 

  • Nunez V, Cid P, Sanz L, De La Torre P, Angulo Y, Lomonte B, Gutierrez JM, Calvete JJ. Snake venomics and antivenomics of Bothrops atrox venoms from Colombia and the Amazon regions of Brazil, Peru and Ecuador suggest the occurrence of geographic variation of venom phenotype by a trend towards paedomorphism. J Proteomics. 2009;73:57–78.

    Article  CAS  PubMed  Google Scholar 

  • Oerke EC, Dehne HW. Safeguarding production – losses in major crops and the role of crop protection. Crop Prot. 2004;23:275–85.

    Article  Google Scholar 

  • Ohno M, Menez R, Ogawa T, Danse JM, Shimohigashi Y, Fromen C, Ducancel F, Zinn-Justin S, Le Du MH, Boulain JC, et al. Molecular evolution of snake toxins: is the functional diversity of snake toxins associated with a mechanism of accelerated evolution? Prog Nucleic Acid Res Mol Biol. 1998;59:307–64.

    Article  CAS  PubMed  Google Scholar 

  • Olivera BM, Walker C, Cartier GE, Hooper D, Santos AD, Schoenfeld R, Shetty R, Watkins M, Bandyopadhyay P, Hillyard DR. Speciation of cone snails and interspecific hyperdivergence of their venom peptides. Potential evolutionary significance of introns. Ann N Y Acad Sci. 1999;870:223–37.

    Article  CAS  PubMed  Google Scholar 

  • Owen MD, Sloley BD. 5-hydroxytryptamine in the venom of the honey bee (Apis mellifera l.): variation with season and with insect age. Toxicon. 1988;26:577–81.

    Article  CAS  PubMed  Google Scholar 

  • Patlak M. From viper’s venom to drug design: treating hypertension. FASEB J. 2004;18:421.

    Article  CAS  PubMed  Google Scholar 

  • Pawlak J, Mackessy SP, Fry BG, Bhatia M, Mourier G, Fruchart-Gaillard C, Servent D, Menez R, Stura E, Menez A, et al. Denmotoxin, a three-finger toxin from the colubrid snake boiga dendrophila (mangrove catsnake) with bird-specific activity. J Biol Chem. 2006;281:29030–41.

    Article  CAS  PubMed  Google Scholar 

  • Pennington MW, Harunur Rashid M, Tajhya RB, Beeton C, Kuyucak S, Norton RS. A c-terminally amidated analogue of shk is a potent and selective blocker of the voltage-gated potassium channel kv1.3. FEBS Lett. 2012;586:3996–4001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Phelan MA, Blanquet RS. Characterization of nematocyst proteins from the sea anemones Aiptasia pallida and pachycerianthus torreyi (Cnidaria: Anthozoa). Comp Biochem Physiol B. 1985;81:661–6.

    CAS  PubMed  Google Scholar 

  • Pond SL, Frost SD, Muse SV. Hyphy: hypothesis testing using phylogenies. Bioinformatics. 2005;21:676–9.

    Article  CAS  PubMed  Google Scholar 

  • Radman M. Enzymes of evolutionary change. Nature. 1999;401:866–7, 869.

    Google Scholar 

  • Reyes-Velasco J, Card DC, Andrew AL, Shaney KJ, Adams RH, Schield DR, Casewell NR, Mackessy SP, Castoe TA. Expression of venom gene homologs in diverse python tissues suggests a new model for the evolution of snake venom. Mol Biol Evol. 2014. doi:10.1093/molbev/msu294.

    Google Scholar 

  • Robuck PR, Wurzelmann JI. Understanding the drug development process. Inflamm Bowel Dis. 2005;11 Suppl 1:S13–6.

    Article  PubMed  Google Scholar 

  • Ruder T, Sunagar K, Undheim EA, Ali SA, Wai TC, Low DH, Jackson TN, King GF, Antunes A, Fry BG. Molecular phylogeny and evolution of the proteins encoded by coleoid (cuttlefish, octopus, and squid) posterior venom glands. J Mol Evol. 2013;76:192–204.

    Article  CAS  PubMed  Google Scholar 

  • Servent D, Winckler-Dietrich V, Hu H-Y, Kessler P, Drevet P, Bertrand D, Ménez A. Only snake curaremimetic toxins with a fifth disulfide bond have high affinity for the neuronal α7 nicotinic receptor. J Biol Chem. 1997;272:24279–86.

    Article  CAS  PubMed  Google Scholar 

  • Sollod BL, Wilson D, Zhaxybayeva O, Gogarten JP, Drinkwater R, King GF. Were arachnids the first to use combinatorial peptide libraries? Peptides. 2005;26:131–9.

    Article  CAS  PubMed  Google Scholar 

  • Sunagar K, Johnson WE, O’Brien SJ, Vasconcelos V, Antunes A. Evolution of crisps associated with toxicoferan-reptilian venom and mammalian reproduction. Mol Biol Evol. 2012;29:1807–22.

    Article  CAS  PubMed  Google Scholar 

  • Sunagar K, Jackson TN, Undheim EA, Ali SA, Antunes A, Fry BG. Three-fingered ravers: rapid accumulation of variations in exposed residues of snake venom toxins. Toxins. 2013a;5:2172–208.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sunagar K, Fry BG, Jackson TN, Casewell NR, Undheim EA, Vidal N, Ali SA, King GF, Vasudevan K, Vasconcelos V, et al. Molecular evolution of vertebrate neurotrophins: co-option of the highly conserved nerve growth factor gene into the advanced snake venom arsenal. PLoS One. 2013b;8:e81827.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sunagar K, Undheim EA, Scheib H, Gren EC, Cochran C, Person CE, Koludarov I, Kelln W, Hayes WK, King GF, et al. Intraspecific venom variation in the medically significant southern pacific rattlesnake (Crotalus oreganus helleri): biodiscovery, clinical and evolutionary implications. J Proteomics. 2014;99:68–83.

    Article  CAS  PubMed  Google Scholar 

  • Takeya H, Arakawa M, Miyata T, Iwanaga S, Omori-Satoh T. Primary structure of h2-proteinase, a non-hemorrhagic metalloproteinase, isolated from the venom of the habu snake, Trimeresurus flavoviridis. J Biochem. 1989;106:151–7.

    CAS  PubMed  Google Scholar 

  • Veiga SS, Gremski W, dos Santos VL, Feitosa L, Mangili OC, Nader HB, Dietrich CP, Brentani RR. Oligosaccharide residues of loxosceles intermedia (brown spider) venom proteins: dependence on glycosylation for dermonecrotic activity. Toxicon. 1999;37:587–607.

    Article  CAS  PubMed  Google Scholar 

  • Vest DK. Envenomation by Tegenaria agrestis (Walckenaer) spiders in rabbits. Toxicon. 1987;25:221–4.

    Article  CAS  PubMed  Google Scholar 

  • von Reumont BM, Blanke A, Richter S, Alvarez F, Bleidorn C, Jenner RA. The first venomous crustacean revealed by transcriptomics and functional morphology: Remipede venom glands express a unique toxin cocktail dominated by enzymes and a neurotoxin. Mol Biol Evol. 2014;31:48–58.

    Article  CAS  Google Scholar 

  • Vonk FJ, Casewell NR, Henkel CV, Heimberg AM, Jansen HJ, McCleary RJ, Kerkkamp HM, Vos RA, Guerreiro I, Calvete JJ, et al. The king cobra genome reveals dynamic gene evolution and adaptation in the snake venom system. Proc Natl Acad Sci U S A. 2013;110:20651–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wagstaff SC, Laing GD, Theakston RD, Papaspyridis C, Harrison RA. Bioinformatics and multiepitope DNA immunization to design rational snake antivenom. PLoS Med. 2006;3:e184.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Welker S, Markert Y, Koditz J, Mansfeld J, Ulbrich-Hofmann R. Disulfide bonds of phospholipase a2 from bee venom yield discrete contributions to its conformational stability. Biochimie. 2011;93:195–201.

    Article  CAS  PubMed  Google Scholar 

  • Yang Z. Likelihood ratio tests for detecting positive selection and application to primate lysozyme evolution. Mol Biol Evol. 1998;15:568–73.

    Article  CAS  PubMed  Google Scholar 

  • Yang Z. Paml 4: phylogenetic analysis by maximum likelihood. Mol Biol Evol. 2007;24:1586–91.

    Article  CAS  PubMed  Google Scholar 

  • Yang Z, Nielsen R. Codon-substitution models for detecting molecular adaptation at individual sites along specific lineages. Mol Biol Evol. 2002;19:908–17.

    Article  CAS  PubMed  Google Scholar 

  • Yang Z, Nielsen R, Goldman N, Pedersen AM. Codon-substitution models for heterogeneous selection pressure at amino acid sites. Genetics. 2000;155:431–49.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yang Z, Wong WS, Nielsen R. Bayes empirical bayes inference of amino acid sites under positive selection. Mol Biol Evol. 2005;22:1107–18.

    Article  CAS  PubMed  Google Scholar 

  • Zelanis A, Serrano SM, Reinhold VN. N-glycome profiling of Bothrops jararaca newborn and adult venoms. J Proteomics. 2012;75:774–82.

    Article  CAS  PubMed  Google Scholar 

  • Zhang J, Nielsen R, Yang Z. Evaluation of an improved branch-site likelihood method for detecting positive selection at the molecular level. Mol Biol Evol. 2005;22:2472–9.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgment

KS was supported by a postdoctoral fellowship from the Council for Higher Education in Israel and the Hebrew University. NRC acknowledges support from the UK Natural Environment Research Council. AA was partially supported by the European Regional Development Fund (ERDF) through the COMPETE – Operational Competitiveness Programme – and national funds through F.C.T under the projects PEst-C/MAR/LA0015/2013 and PTDC/AAC-AMB/121301/2010 (FCOMP-01-0124-FEDER-019490). This research was supported by the Israel Science Foundation grant No. 691/14 to YM.

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Authors and Affiliations

  1. The Alexander Silberman Institute for Life Sciences, The Department of Ecology, Evolution and Behavior, The Hebrew University of Jerusalem, Givat Ram, 9190401, Jerusalem, Israel

    Kartik Sunagar & Yehu Moran

  2. Alistair Reid Venom Research Unit, Liverpool School of Tropical Medicine, Liverpool, UK

    Nicholas R. Casewell

  3. Madras Crocodile Bank Trust/Centre for Herpetology, Vadanemelli Village, ECR, 603 104, Mamallapuram, Tamil Nadu, India

    Sandeep Varma

  4. Boehringer Ingelheim India Pvt. Ltd, Bengaluru, Karnataka, India

    Rohan Kolla

  5. CIIMAR/CIMAR – Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Rua dos Bragas, 177, 4050-123, Porto, Portugal

    Agostinho Antunes

  6. Department of Biology, Faculty of Sciences, University of Porto, Porto, Portugal

    Agostinho Antunes

Authors
  1. Kartik Sunagar
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  2. Nicholas R. Casewell
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  3. Sandeep Varma
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  4. Rohan Kolla
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  5. Agostinho Antunes
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  6. Yehu Moran
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Corresponding author

Correspondence to Kartik Sunagar .

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Editors and Affiliations

  1. Venom and Toxin Research Programme, Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    P. Gopalakrishnakone

  2. Structural and Functional Venomics Lab, Instituto de Biomedicina de Valencia (CSIC), Valencia, Spain

    Juan J. Calvete

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Sunagar, K., Casewell, N.R., Varma, S., Kolla, R., Antunes, A., Moran, Y. (2016). Deadly Innovations: Unraveling the Molecular Evolution of Animal Venoms. In: Gopalakrishnakone, P., Calvete, J. (eds) Venom Genomics and Proteomics. Toxinology. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6416-3_27

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