Animal Venoms: Origin, Diversity and Evolution

Abstract

Venomous animals and their venoms have intrigued mankind for millennia. Venoms are complex cocktails of chemically diverse components that disrupt the physiological functioning of the victim to aid the venom‐producing animal in defence and/or feeding. Despite evolving independently on at least 30 occasions in the animal kingdom, venom exhibits remarkable evolutionary convergence, both in composition and biochemical activity. Various factors, including geography, diet, predator pressure, evolutionary arms race and phylogenetic history, underpin the diversification of venoms. Certain venomous animals, particularly snakes, are medically important and are responsible for tens of thousands of permanent loss‐of‐function injuries and deaths in humans every year. At the same time, as venom harbours many bioactive and highly specific components, it has tremendous potential applications in the development of novel lifesaving therapeutics and environment‐friendly agrochemicals. Several wonder drugs based on venom proteins have saved millions of lives worldwide, and many others are in development.

Key Concepts

  • Venom has evolved independently ∼30 times in the animal kingdom to assist the venom‐producing animal in self‐defence and/or prey capture.
  • A remarkable convergence can be observed in the composition and bioactivity of venoms.
  • While most animals modified their salivary glands into venom glands, the duck‐billed platypus and echidna evolved venom glands through the evolutionary tinkering of sweat glands.
  • Cnidarians evolved peculiar cell types to inject venom into their victims, while many hymenopterans have modified their ovipositors for venom injection.
  • The strong influence of positive Darwinian selection has driven the evolutionary diversification of venoms, while the structural integrity is conserved by purifying selection.

Keywords: venoms; poisons; toxins; evolution; venom delivery system; therapeutics

Figure 1. Parallel origins of animal venom. The tree of life, based on Casewell et al. (), is depicted here, indicating the multiple origins of venom in animals. Venoms used for defence, predation or intraspecific competition are indicated in blue‐, red‐ and orange‐coloured branches, respectively.
Figure 2. Diverse mechanisms of venom delivery in the animal kingdom. This figure portrays venom delivery in (a) Cnidaria – jellyfish with nematocytes; (b) Gastropoda – cone snail with a harpoon; (c) Echinodermata – starfish with dorsal spines; (d) Hirudinea – leech with the suctorial disc and (e) Polychaeta –Glycera worm with the mineralised jaw.
Figure 3. Diverse mechanisms of venom delivery in the animal kingdom. This figure portrays venom delivery in (a) Cephalopoda – octopus with beak; (b) Arachanida – scorpion with stinger; (c) Arachanida – tarantula with fangs; (d) Hymenoptera – wasp with stinger; (e) Chilopoda – Scolopendra centipede with forcipules and (f) Hemiptera – assassin bug with a proboscis.
Figure 4. Diverse mechanisms of venom delivery in the animal kingdom. This figure portrays venom delivery in (a) Blennoid – fangblenny with mandibular fangs; (b) Synanceia – stonefish with dorsal spines; (c) stingray with stinger; (d) Aparasphenodon and its forehead spines; (e) Pit viper with maxillary fangs and (f) Varanus lizard with mandibular fangs.
Figure 5. Diverse mechanisms of venom delivery in the animal kingdom. This figure portrays venom delivery in (a) duck‐billed platypus and its spur and (b) vampire bat with incisors and the tongue.
Figure 6. Molecular evolution of venom. This figure describes the homology model of elapid three‐finger toxins, where positively selected sites are indicated in red. A colour code is provided to depict selection pressures experienced by other residues. A sequence alignment has also been provided, where the signal and mature peptides are indicated, along with the sites that exhibit greater than 90% sequence identity (blue) and those that experience positive selection (red).
close

References

Abdel‐Rahman MA , Omran MA , Abdel‐Nabi IM , Ueda H and McVean A (2009) Intraspecific variation in the Egyptian scorpion Scorpio maurus palmatus venom collected from different biotopes. Toxicon 53 (3): 349–359. 10.1016/j.toxicon.2008.12.007.

Barlow A , Pook CE , Harrison RA and Wuster W (2009) Coevolution of diet and prey‐specific venom activity supports the role of selection in snake venom evolution. Proceedings of the Royal Society B: Biological Sciences 276 (1666): 2443–2449. http://rspb.royalsocietypublishing.org/cgi/doi/10.1098/rspb.2009.0048.

Benkhadir K , Kharrat R , Cestèle S , et al. (2004) 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 25 (2): 151–161.

Benoit J , Norton LA , Manger PR and Rubidge BS (2017) Reappraisal of the envenoming capacity of Euchambersia mirabilis (Therapsida, Therocephalia) using μCT‐scanning techniques. PLoS One 12 (2): e0172047. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0172047.

Bourgeois M (1961) Atractaspis–a misfit among the Viperidae. News Bulletin of the Zoological Society of South Africa 3: 29.

Brust A , Sunagar K , Undheim EAB , et al. (2013) Differential evolution and neofunctionalization of snake venom metalloprotease domains. Molecular & Cellular Proteomics 12 (3): 651–663. http://www.mcponline.org/content/12/3/651.full.

Casewell NR , Wüster W , Vonk FJ , Harrison RA and Fry BG (2013) Complex cocktails: the evolutionary novelty of venoms. Trends in Ecology & Evolution 28 (4): 219–229.

Casewell NR , Visser JC , Baumann K , et al. (2017) The evolution of fangs, venom, and mimicry systems in blenny fishes. Current Biology 27 (8): 1184–1191. http://www.venomdoc.com/s/2017‐Fang‐blenny.pdf.

Clarke BT (1997) The natural history of amphibian skin secretions, their normal functioning and potential medical applications. Biological Reviews 72 (3): 365–379. https://www.cambridge.org/core/journals/biological‐reviews/article/the‐natural‐history‐of‐amphibian‐skin‐secretions‐their‐normal‐functioning‐and‐potential‐medical‐applications/B7F478B74B87845930279EDBFD8E4EB2.

Craig AG , Bandyopadhyay and Olivera BM (1999) Post‐translationally modified neuropeptides from Conus venoms. European Journal of Biochemistry 264 (2): 271–275.

Owen MD and Sloley BD (1988) 5‐Hydroxytryptamine in the venom of the honey bee (Apis mellifera L.): variation with season and with insect age. Toxicon 26 (6): 577–581.

Dugon MM and Arthur W (2012) Prey orientation and the role of venom availability in the predatory behaviour of the centipede Scolopendra subspinipes mutilans (Arthropoda: Chilopoda). Journal of Insect Physiology 58 (6): 874–880. http://www.sciencedirect.com/science/article/pii/S0022191012000789.

Durban J , Juárez P , Angulo Y , et al. (2011) Profiling the venom gland transcriptomes of Costa Rican snakes by 454 pyrosequencing. BMC Genomics 12 (1): 259. http://bmcgenomics.biomedcentral.com/articles/10.1186/1471‐2164‐12‐259.

Dutertre S , Jin A‐H , Vetter I , et al. (2014) Evolution of separate predation‐ and defence‐evoked venoms in carnivorous cone snails. Nature Communications 5: 3521. http://www.nature.com/doifinder/10.1038/ncomms4521.

Earl STH , Birrell GW , Wallis TP , et al. (2006) Post‐translational modification accounts for the presence of varied forms of nerve growth factor in Australian elapid snake venoms. Proteomics 6 (24): 6554–6565.

Fauchald K and Jumars PA (1979) The Diet of Worms: A Study of Polychaete Feeding Guilds, vol. 17. Aberdeen University Press. https://www.researchgate.net/profile/Peter_Jumars/publication/255608624_The_Diet_of_Worms_A_Study_of_Polychaete_Feeding_Guilds/links/02e7e5371f8f32da46000000.pdf.

Fry BG , Vidal N , Norman JA , et al. (2006) Early evolution of the venom system in lizards and snakes. Nature 439 (7076): 584–588. http://www.nature.com/doifinder/10.1038/nature04328.

Fry BG , Roelants K , Champagne D , et al. (2009) The toxicogenomic multiverse: convergent recruitment of proteins into animal venoms. Annual Review of Genomics and Human Genetics 10: 483–511. http://www.annualreviews.org/doi/full/10.1146/annurev.genom.9.081307.164356.

Fry BG , Sunagar K , Casewell N , et al. (2015) The origin and evolution of the Toxicofera reptile venom system. In: Fry BG (ed) Venomous Reptiles and Their Toxins: Evolution, Pathophysiology and Biodiscovery, pp. 1–31. New York: Oxford University Press.

Huang CC , Stricher F , Martin L , et al. (2005) Scorpion‐toxin mimics of CD4 in complex with human immunodeficiency virus gp120: crystal structures, molecular mimicry, and neutralization breadth. Structure 13 (5): 755–768.

Inceoglu B , Lango J , Jing J , et al. (2003) One scorpion, two venoms: prevenom of Parabuthus transvaalicus acts as an alternative type of venom with distinct mechanism of action. Proceedings of the National Academy of Sciences of the United States of America 100 (3): 922–927. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=298702&tool=pmcentrez&rendertype=abstract.

Jared C , Mailho‐Fontana PL , Antoniazzi MM , et al. (2015) Venomous frogs use heads as weapons. Current Biology 25 (16): 2166–2170. http://www.sciencedirect.com/science/article/pii/S0960982215007885.

Jouiaei M , Sunagar K , Federman Gross A , et al. (2015) Evolution of an ancient venom: recognition of a novel family of cnidarian toxins and the common evolutionary origin of sodium and potassium neurotoxins in sea anemone. Molecular Biology and Evolution 32 (6): 1598–1610.

Kasturiratne A , Wickremasinghe AR , de Silva N , et al. (2008) The global burden of snakebite: a literature analysis and modelling based on regional estimates of envenoming and deaths. PLoS Medicine 5 (11): e218. http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.0050218.

Low DHW , Sunagar K , Undheim EAB , et al. (2013) Dracula's children: molecular evolution of vampire bat venom. Journal of Proteomics 89: 95–111. 10.1016/j.jprot.2013.05.034.

Martinson EO , Mrinalini , Kelkar YD , et al. (2017) The evolution of venom by co‐option of single‐copy genes. Current Biology 27 (13): 2007–2013.e8. 10.1016/j.cub.2017.05.032.

Miller DW , Jones AD , Goldston JS , Rowe MP and Rowe AH (2016) Sex differences in defensive behavior and venom of the striped bark scorpion Centruroides vittatus (Scorpiones: Buthidae). Integrative and Comparative Biology 56 (5): 1022–1031.

Nekaris KAI , Moore RS , Rode EJ and Fry BG (2013) Mad, bad and dangerous to know: the biochemistry, ecology and evolution of slow loris venom. Journal of Venomous Animals and Toxins Including Tropical Diseases 19 (1): 21. https://jvat.biomedcentral.com/articles/10.1186/1678‐9199‐19‐21.

Reyes‐Velasco J , Card DC , Andrew AL , et al. (2015) Expression of venom gene homologs in diverse python tissues suggests a new model for the evolution of snake venom. Molecular Biology and Evolution 32 (1): 173–183.

Rowe AH , Xiao Y , Rowe MP , et al. (2013) Voltage‐gated sodium channel in grasshopper mice defends against bark scorpion toxin. Science 342 (6157): 441–446.

Schmidtko A , Lötsch J , Freynhagen R and Geisslinger G (2010) Ziconotide for treatment of severe chronic pain. The Lancet 375 (9725): 1569–1577. 10.1016/S0140-6736(10)60354-6.

Sheumack DD , Howden ME , Spence I and Quinn RJ (1978) Maculotoxin: a neurotoxin from the venom glands of the octopus Hapalochlaena maculosa identified as tetrodotoxin. Science (New York, N.Y.) 199 (4325): 188–189. http://www.ncbi.nlm.nih.gov/pubmed/619451.

Smith WL and Wheeler WC (2006) Venom evolution widespread in fishes: a phylogenetic road map for the bioprospecting of piscine venoms. Journal of Heredity 97 (3): 206–217. https://academic.oup.com/jhered/article/97/3/206/DQ532831.

Starcevic A and Long PF (2013) Diversification of animal venom peptides – were jellyfish amongst the first combinatorial chemists? ChemBioChem 14 (12): 1407–1409. http://onlinelibrary.wiley.com/doi/10.1002/cbic.201300305/abstract.

Sunagar K , Jackson TN , Undheim EA , et al. (2013) Three‐fingered RAVERs: rapid accumulation of variations in exposed residues of snake venom toxins. Toxins 5 (11): 2172–2208.

Sunagar K , Undheim EA , Scheib H , et al. (2014) Intraspecific venom variation in the medically significant Southern Pacific Rattlesnake (Crotalus oreganus helleri): biodiscovery, clinical and evolutionary implications. Journal of Proteomics 99: 68–83.

Sunagar K and Moran Y (2015) The rise and fall of an evolutionary innovation: contrasting strategies of venom evolution in ancient and young animals. PLoS Genetics 11 (10): 1–20.

Sunagar K , Casewell NR , Varma S , et al. (2016) Deadly innovations: unraveling the molecular evolution of animal venoms. In: Gopalakrishnakone P and Calvete JJ (eds) Venom Genomics and Proteomics, pp. 1–27. Dordrecht: Springer.

Sunagar K , Columbus‐Shenkar Y , Fridrich A et al. (2017) Cell type‐specific expression profiling sheds light on the development of a peculiar neuron, housing a complex organelle. bioRxiv. Retrieved from http://biorxiv.org/content/early/2017/06/30/158063.abstract

Szaniawski H (2009) The earliest known venomous animals recognized among conodonts. Acta Palaeontologica Polonica 54 (4): 669–676. http://www.bioone.org/doi/full/10.4202/app.2009.0045.

Takasaki C , Tamiya N , Bdolah A , et al. (1988) Sarafotoxins S6: several isotoxins from Atractaspis engaddensis (burrowing asp) venom that affect the heart. Toxicon 26 (6): 543–548.

Terrat Y , Sunagar K , Fry BG , et al. (2013) Atractaspis aterrima toxins: The first insight into the molecular evolution of venom in side‐stabbers. Toxins 5 (11): pp. 1948–1964.

Vetrano SJ , Lebowitz JB and Marcus S (2002) Lionfish envenomation. The Journal of Emergency Medicine 23 (4): 379–382. http://www.sciencedirect.com/science/article/pii/S0736467902005723.

Watanabe A , Nagai H , Nagashima Y and Shiomi K (2009) Structural characterization of plancitoxin I, a deoxyribonuclease II‐like lethal factor from the crown‐of‐thorns starfish Acanthaster planci, by expression in Chinese hamster ovary cells. Fisheries Science 75 (1): 225–231. https://link.springer.com/article/10.1007/s12562‐008‐0004‐x.

Whittington CM , Papenfuss A , Bansal P , et al. (2008) Defensins and the convergent evolution of platypus and reptile venom genes. Genome Research 18 (6): 986–994. http://genome.cshlp.org/content/18/6/986.full.html.

Further Reading

Bücherl W , Buckley EE and Deulofeu V (eds) (2013) Venomous Animals and Their Venoms: Venomous Vertebrates. Amsterdam, Netherlands: Elsevier.

Fry BG , Koludarov I , Jackson TNW , et al. (2015) Seeing the woods for the trees: understanding venom evolution as a guide for biodiscovery. In: King GF (ed) Venoms to Drugs: Venom as a Source for the Development of Human Therapeutics, pp. 1–36. Cambridge, UK: The Royal Society of Chemistry.

Gopalakrishnakone P and Calvete JJ (eds) (2016) Venom Genomics and Proteomics. Dordrecht: Springer.

Jenner R and Undheim E (2017) The Secrets of Nature's Deadliest Weapon. CSIRO Publishing, ISBN: 9781486308378.

King G (ed) (2015) Venoms to Drugs: Venom as a Source for the Development of Human Therapeutics. London: Royal Society of Chemistry.

Mackessy SP (ed) (2016) Handbook of Venoms and Toxins of Reptiles. Florida, United States: CRC Press.

von Reumont BM , Campbell LI and Jenner RA (2014) Quo Vadis Venomics? A roadmap to neglected venomous invertebrates. Toxins 6 (12): 3488–3551. http://www.mdpi.com/2072‐6651/6/12/3488.

Shiomi K , Midorikawa S , Ishida M , Nagashima Y and Nagai H (2004) Plancitoxins, lethal factors from the crown‐of‐thorns starfish Acanthaster planci, are deoxyribonucleases II. Toxicon 44 (5): 499–506. http://www.sciencedirect.com/science/article/pii/S004101010400282X.

Sues H‐D (1996) A reptilian tooth with apparent venom canals from the Chinle Group (Upper Triassic) of Arizona. Journal of Vertebrate Paleontology 16 (3): 571–572. http://www.tandfonline.com/doi/pdf/10.1080/02724634.1996.10011340.

Undheim EAB and King GF (2011) On the venom system of centipedes (Chilopoda), a neglected group of venomous animals. Toxicon 57 (4): 512–524. http://www.sciencedirect.com/science/article/pii/S0041010111000092.

Williams BL (2010) Behavioral and chemical ecology of marine organisms with respect to tetrodotoxin. Marine Drugs 8 (3): 381–398. http://www.mdpi.com/1660‐3397/8/3/381/htm.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Suranse, Vivek, Srikanthan, Achyuthan, and Sunagar, Kartik(Mar 2018) Animal Venoms: Origin, Diversity and Evolution. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000939.pub2]