venom

{{Further|Evolution of snake venom}}

The use of venom across a wide variety of taxa is an example of convergent evolution. In animals, venom usage has evolved independently for at least 104 times, across 8 phyla (body plans). It is difficult to conclude exactly how this trait came to be so intensely widespread and diversified. The multigene families that encode the toxins of venomous animals are actively selected, creating more diverse toxins with specific functions. Venoms adapt to their environment and victims, evolving to become maximally efficient on a predator's particular prey (particularly the precise ion channels within the prey). Consequently, venoms become specialized to an animal's standard diet.{{cite journal |last1=Kordiš |first1=D. |last2=Gubenšek |first2=F. |year=2000 |title=Adaptive evolution of animal toxin multigene families |journal=Gene |volume=261 |issue=1 |pages=43–52 |doi=10.1016/s0378-1119(00)00490-x |pmid=11164036 }}

{{Main|Toxin}}

File:1poc.png, an enzyme in bee venom, releases fatty acids, affecting calcium signalling.]]

Venoms cause their biological effects via the many toxins that they contain; some venoms are complex mixtures of toxins of differing types. Major classes of toxin in venoms include:{{cite journal |last=Harris |first=J. B. |title=Animal poisons and the nervous system: what the neurologist needs to know |journal=Journal of Neurology, Neurosurgery & Psychiatry |volume=75 |issue=suppl_3 |date=September 2004 |doi=10.1136/jnnp.2004.045724 |pmid=15316044 |pmc=1765666 |pages=iii40–iii46}}

• Necrotoxins, which cause necrosis (i.e., death) in the cells they encounter. The venoms of vipers and bees contain phospholipases; viper venoms often also contain trypsin-like serine proteases.{{cite journal |last1=Raffray |first1=M. |first2=G. M. |title=Apoptosis and necrosis in toxicology: a continuum or distinct modes of cell death? |journal=Pharmacology & Therapeutics |volume=75 |issue=3 |pages=153–177 |year=1997 |pmid=9504137 |doi=10.1016/s0163-7258(97)00037-5 |last2=Cohen}}
• Neurotoxins, which primarily affect the nervous systems of animals, such as ion channel toxins. These are found in many venomous taxa, including mambas,{{cite web|url=http://cogs.csustan.edu/~tom/bioinfo/groupwork/cobra/cobra-venom.ppt|title=Neurotoxins in Snake Venom|access-date=2019-12-26}} black widow spiders, scorpions, box jellyfish, cone snails, centipedes and blue-ringed octopuses.{{cite journal |last1=Dutertre |first1=Sébastien |last2=Lewis |first2=Richard J. |title=Toxin insights into nicotinic acetylcholine receptors |journal=Biochemical Pharmacology |volume=72 |issue=6 |year=2006 |doi=10.1016/j.bcp.2006.03.027 |pmid=16716265 |pages=661–670}}
• Myotoxins, which damage muscles by binding to a receptor. These small, basic peptides are found in snake (such as rattlesnake) and lizard venoms.{{cite journal |last1=Nicastro |first1=G. |others=Franzoni, L.; de Chiara, C.; Mancin, A. C.; Giglio, J. R.; Spisni, A. |title=Solution structure of crotamine, a Na+ channel affecting toxin from Crotalus durissus terrificus venom |journal=Eur. J. Biochem. |volume=270 |issue=9 |pages=1969–1979 |date=May 2003 |pmid=12709056 |doi=10.1046/j.1432-1033.2003.03563.x |s2cid=20601072 |doi-access=free }}{{cite journal |last1=Griffin |first1=P. R. |last2=Aird |first2=S. D. |title=A new small myotoxin from the venom of the prairie rattlesnake (Crotalus viridis viridis) |journal=FEBS Letters |volume=274 |issue=1 |pages=43–47 |year=1990 |pmid=2253781 |doi=10.1016/0014-5793(90)81325-I|s2cid=45019479 |doi-access=free |bibcode=1990FEBSL.274...43G }}{{cite journal |last1=Samejima |first1=Y. |last2=Aoki |first2=Y. |last3=Mebs |first3=D. |title=Amino acid sequence of a myotoxin from venom of the eastern diamondback rattlesnake (Crotalus adamanteus) |journal=Toxicon |volume=29 |issue=4 |pages=461–468 |year=1991 |pmid=1862521 |doi=10.1016/0041-0101(91)90020-r|bibcode=1991Txcn...29..461S }}{{cite journal |last1=Whittington |first1=C. M. |last2=Papenfuss |first2=A. T. |last3=Bansal |first3=P. |last4=Torres |first4=A. M. |last5=Wong |first5=E. S. |last6=Deakin |first6=J. E. |last7=Graves |first7=T. |last8=Alsop |first8=A. |last9=Schatzkamer |first9=K. |last10=Kremitzki |first10=C. |last11=Ponting |first11=C. P. |last12=Temple-Smith |first12=P. |last13=Warren |first13= W. C.|last14=Kuchel |first14=P. W. |last15=Belov |first15=K. |display-authors=3 |title=Defensins and the convergent evolution of platypus and reptile venom genes |journal=Genome Research |date=June 2008 |volume=18 |issue=6 |pages=986–094 |pmid=18463304 |doi=10.1101/gr.7149808 |pmc=2413166 }}
• Cytotoxins, which kill individual cells and are found in the apitoxin of honey bees and the venom of black widow spiders.{{cite journal |last1=Sobral |first1=Filipa |last2=Sampaio |first2=Andreia |last3=Falcão |first3=Soraia |last4=Queiroz |first4=Maria João R.P. |last5=Calhelha |first5=Ricardo C. |last6=Vilas-Boas |first6=Miguel |last7=Ferreira |first7=Isabel C. F. R. |display-authors=3 |title=Chemical characterization, antioxidant, anti-inflammatory and cytotoxic properties of bee venom collected in Northeast Portugal |journal=Food and Chemical Toxicology |volume=94 |year=2016 |doi=10.1016/j.fct.2016.06.008 |pmid=27288930 |pages=172–177 |hdl=10198/13492 |s2cid=21796492 |url=https://bibliotecadigital.ipb.pt/bitstream/10198/13492/3/345.pdf }}{{cite journal |last1=Peng |first1=Xiaozhen |last2=Dai |first2=Zhipan |last3=Lei |first3=Qian |last4=Liang |first4=Long |last5=Yan |first5=Shuai |last6=Wang |first6=Xianchun |display-authors=3 |title=Cytotoxic and apoptotic activities of black widow spiderling extract against HeLa cells |journal=Experimental and Therapeutic Medicine |volume=13 |issue=6 |date=April 2017 |doi=10.3892/etm.2017.4391 |pmid=28587399 |pmc=5450530 |pages=3267–3274}}

Venom is widely distributed taxonomically, being found in both invertebrates and vertebrates, in aquatic and terrestrial animals, and among both predators and prey. The major groups of venomous animals are described below.

Venomous arthropods include spiders, which use fangs on their chelicerae to inject venom, and centipedes, which use {{nowrap|forcipules{{tsp}}{{mdash}}{{tsp}}}}modified {{nowrap|legs{{tsp}}{{mdash}}{{tsp}}}}to deliver venom, while scorpions and stinging insects inject venom with a sting. In bees and wasps, the stinger is a modified ovipositor (egg-laying device). In Polistes fuscatus, the female continuously releases a venom that contains a sex pheromone that induces copulatory behavior in males.{{cite journal |last=Post Downing |first=Jeanne |year=1983 |title=Venom: Source of a Sex Pheromone in the Social Wasp Polistes fuscatus (Hymenoptera: Vespidae) |journal=Journal of Chemical Ecology |volume=9 |issue=2 |pages=259–266 |doi=10.1007/bf00988043 |pmid=24407344 |bibcode=1983JCEco...9..259P |s2cid=32612635 }} In wasps such as Polistes exclamans, venom is used as an alarm pheromone, coordinating a response from the nest and attracting nearby wasps to attack the predator.{{cite journal |last=Post Downing |first=Jeanne |year=1984 |title=Alarm response to venom by social wasps Polistes exclamans and P. fuscatus |journal=Journal of Chemical Ecology |volume=10 |issue=10 |pages=1425–1433 |doi=10.1007/BF00990313 |pmid=24318343 |s2cid=38398672 }} In some species, such as Parischnogaster striatula, venom is applied all over the body as an antimicrobial protection.{{Cite journal |title=From individual to collective immunity: The role of the venom as antimicrobial agent in the Stenogastrinae wasp societies |last=Baracchi |first=David |date=January 2012 |journal=Journal of Insect Physiology |doi=10.1016/j.jinsphys.2011.11.007 |pmid=22108024 |volume=58 |issue=1 |pages=188–193 |bibcode=2012JInsP..58..188B |hdl=2158/790328 |s2cid=206185438 |hdl-access=free }}

Many caterpillars have defensive venom glands associated with specialized bristles on the body called urticating hairs. These are usually merely irritating, but those of the Lonomia moth can be fatal to humans.{{cite journal |last1=Pinto |first1=Antônio F. M. |last2=Berger |first2=Markus |last3=Reck |first3=José |last4=Terra |first4=Renata M. S. |last5=Guimarães |first5=Jorge A. |title=Lonomia obliqua venom: In vivo effects and molecular aspects associated with the hemorrhagic syndrome |journal=Toxicon |volume=56 |issue=7 |date=15 December 2010 |pmid=20114060 |doi=10.1016/j.toxicon.2010.01.013 |pages=1103–1112|bibcode=2010Txcn...56.1103P }}

Bees synthesize and employ an acidic venom (apitoxin) to defend their hives and food stores, whereas wasps use a chemically different venom to paralyse prey, so their prey remains alive to provision the food chambers of their young. The use of venom is much more widespread than just these examples; many other insects, such as true bugs and many ants, also produce venom.{{Cite journal |last1=Touchard |first1=Axel |last2=Aili |first2=Samira |last3=Fox |first3=Eduardo |last4=Escoubas |first4=Pierre |last5=Orivel |first5=Jérôme |last6=Nicholson |first6=Graham |last7=Dejean |first7=Alain |display-authors=3 |date=20 January 2016 |title=The Biochemical Toxin Arsenal from Ant Venoms |journal=Toxins |volume=8 |issue=1 |page=30 |doi=10.3390/toxins8010030 |pmid=26805882 |pmc=4728552 |issn=2072-6651 |doi-access=free}} The ant species Polyrhachis dives uses venom topically for the sterilisation of pathogens.{{cite journal |last1=Graystock |first1=Peter |last2=Hughes |first2=William O. H. |title=Disease resistance in a weaver ant, Polyrhachis dives, and the role of antibiotic-producing glands |journal=Behavioral Ecology and Sociobiology |year=2011 |doi=10.1007/s00265-011-1242-y |volume=65 |issue=12 |pages=2319–2327|bibcode=2011BEcoS..65.2319G |s2cid=23234351 }}

File:Irukandji-jellyfish-queensland-australia.jpg has among the most dangerous venom of any animal, causing Irukandji syndrome⁠{{nowrap|{{hsp}}{{mdash}}{{hsp}}}}severe pain, vomiting, and rapid rise in blood pressure]]

There are venomous invertebrates in several phyla, including jellyfish such as the dangerous box jellyfish,{{cite magazine |last1=Frost |first1=Emily |title=What's Behind That Jellyfish Sting? |url=https://www.smithsonianmag.com/science-nature/whats-behind-that-jellyfish-sting-2844876/ |magazine=Smithsonian |access-date=30 September 2018 |date=30 August 2013}} the Portuguese man-of-war (a siphonophore) and sea anemones among the Cnidaria,{{cite book |last1=Bonamonte |first1=Domenico |last2=Angelini |first2=Gianni |title=Aquatic Dermatology: Biotic, Chemical and Physical Agents |url=https://books.google.com/books?id=A4cSDQAAQBAJ&pg=PA54 |year=2016 |publisher=Springer International |isbn=978-3-319-40615-2 |pages=54–56}} sea urchins among the Echinodermata,{{Cite journal |last=Gallagher |first=Scott A. |title=Echinoderm Envenomation |url=http://emedicine.medscape.com/article/770053-overview |journal=EMedicine |access-date=12 October 2010 |date=2017-08-02 }} and cone snails{{cite journal |last1=Olivera |first1=B. M. |last2=Teichert |first2=R. W. |title=Diversity of the neurotoxic Conus peptides: a model for concerted pharmacological discovery |journal=Molecular Interventions |year= 2007 |volume= 7 |issue= 5 |pages=251–260 |pmid=17932414 |doi=10.1124/mi.7.5.7}} and cephalopods, including octopuses, among the Molluscs.{{cite magazine |last1=Barry |first1=Carolyn |title=All Octopuses Are Venomous, Study Says |url=https://www.nationalgeographic.com/animals/2009/04/octopus-venom-hunting-cephalopod/ |archive-url=https://web.archive.org/web/20180930193124/https://www.nationalgeographic.com/animals/2009/04/octopus-venom-hunting-cephalopod/ |url-status=dead |archive-date=30 September 2018 |magazine=National Geographic |access-date=30 September 2018 |date=17 April 2009}}

{{Main|Venomous fish}}

Venom is found in some 200 cartilaginous fishes, including stingrays, sharks, and chimaeras; the catfishes (about 1000 venomous species); and 11 clades of spiny-rayed fishes (Acanthomorpha), containing the scorpionfishes (over 300 species), stonefishes (over 80 species), gurnard perches, blennies, rabbitfishes, surgeonfishes, some velvetfishes, some toadfishes, coral crouchers, red velvetfishes, scats, rockfishes, deepwater scorpionfishes, waspfishes, weevers, and stargazers.{{cite journal |last1=Smith |first1=William Leo |last2=Wheeler |first2=Ward C. |title=Venom Evolution Widespread in Fishes: A Phylogenetic Road Map for the Bioprospecting of Piscine Venoms |journal=Journal of Heredity |volume=97 |issue=3 |date=2006 |doi=10.1093/jhered/esj034 |pmid=16740627 |pages=206–217 |doi-access=free }}

Some salamanders can extrude sharp venom-tipped ribs.[http://www.askabiologist.org.uk/punbb/viewtopic.php?id=1494 Venomous Amphibians (Page 1) – Reptiles (Including Dinosaurs) and Amphibians – Ask a Biologist Q&A]. Askabiologist.org.uk. Retrieved on 2013-07-17.{{Cite journal |last1=Nowak |first1=R. T. |last2=Brodie |first2=E. D. |title=Rib Penetration and Associated Antipredator Adaptations in the Salamander Pleurodeles waltl (Salamandridae) |journal=Copeia |volume=1978 |issue=3 |pages=424–429 |year=1978 |doi=10.2307/1443606 |jstor=1443606 }} Two frog species in Brazil have tiny spines around the crown of their skulls which, on impact, deliver venom into their targets.{{Cite journal |date=2015-08-17 |title=Venomous Frogs Use Heads as Weapons |journal=Current Biology |volume=25 |issue=16 |pages=2166–2170 |doi=10.1016/j.cub.2015.06.061 |issn=0960-9822 |last1=Jared |first1=Carlos |last2=Mailho-Fontana |first2=Pedro Luiz |last3=Antoniazzi|first3=Marta Maria |last4=Mendes |first4=Vanessa Aparecida |last5=Barbaro |first5=Katia Cristina |last6=Rodrigues |first6=Miguel Trefau t|last7=Brodie |first7=Edmund D. |display-authors=3 |pmid=26255851 |s2cid=13606620|doi-access=free |bibcode=2015CBio...25.2166J }}

====Reptiles====

{{Further|Big Four (Indian snakes)}}

{{Main|Snake venom|Evolution of snake venom}}

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|footer=The venom of the prairie rattlesnake, Crotalus viridis (left), includes metalloproteinases (example on the right) which help digest prey before eating.

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Some 450 species of snake are venomous. Snake venom is produced by glands below the eye (the mandibular glands) and delivered to the target through tubular or channeled fangs. Snake venoms contain a variety of peptide toxins, including proteases, which hydrolyze protein peptide bonds; nucleases, which hydrolyze the phosphodiester bonds of DNA; and neurotoxins, which disrupt signalling in the nervous system.{{cite book |last=Bauchot |first=Roland |title=Snakes: A Natural History |year=1994 |publisher=Sterling |isbn=978-1-4027-3181-5 |pages=194–209}} Snake venom causes symptoms including pain, swelling, tissue necrosis, low blood pressure, convulsions, haemorrhage (varying by species of snake), respiratory paralysis, kidney failure, coma, and death.{{cite web |title=Snake Bites |url=http://eclinicalworks.adam.com/content.aspx?productId=39&pid=1&gid=000031&print=1 |publisher=A. D. A. M. Inc |access-date=30 September 2018 |date=16 October 2017}} Snake venom may have originated with duplication of genes that had been expressed in the salivary glands of ancestors.{{cite journal |last1=Hargreaves |first1=Adam D. |last2=Swain |first2=Martin T. |last3=Hegarty |first3=Matthew J. |last4=Logan |first4=Darren W. |last5=Mulley |first5=John F. |title=Restriction and Recruitment—Gene Duplication and the Origin and Evolution of Snake Venom Toxins |journal=Genome Biology and Evolution |volume=6 |issue=8 |date=30 July 2014 |doi=10.1093/gbe/evu166 |pmid=25079342 |pmc=4231632 |pages=2088–2095}}{{cite journal |last1=Daltry |first1=Jennifer C. |author2=Wuester, Wolfgang |author3=Thorpe, Roger S. |year=1996 |title=Diet and snake venom evolution |journal=Nature |volume=379 |issue=6565 |pages=537–540 |doi=10.1038/379537a0 |pmid=8596631|bibcode=1996Natur.379..537D |s2cid=4286612 }}

Venom is found in a few other reptiles such as the Mexican beaded lizard,{{cite journal |last=Cantrell |first=F. L. |title=Envenomation by the Mexican beaded lizard: a case report |journal=Journal of Toxicology. Clinical Toxicology |volume=41 |issue=3 |year=2003 |pmid=12807305 |pages=241–244 |doi=10.1081/CLT-120021105 |s2cid=24722441 }} the gila monster, and some monitor lizards, including the Komodo dragon.{{cite journal |last1=Fry |first1=B. G. |author2=Wroe, S. |author3=Teeuwisse, W. |title=A central role for venom in predation by Varanus komodoensis (Komodo Dragon) and the extinct giant Varanus (Megalania) priscus |journal=PNAS |volume=106 |issue=22 |pages=8969–8974 |date=June 2009 |pmid=19451641 |pmc=2690028 |doi=10.1073/pnas.0810883106 |bibcode=2009PNAS..106.8969F |doi-access=free }} Mass spectrometry showed that the mixture of proteins present in their venom is as complex as the mixture of proteins found in snake venom.Fry, B. G.; Wuster, W.; Ramjan, S. F. R.; Jackson, T.; Martelli, P.; Kini, R. M. 2003c. Analysis of Colubroidea snake venoms by liquid chromatography with mass spectrometry: Evolutionary and toxinological implications. Rapid Communications in Mass Spectrometry 17:2047-2062.

Some lizards possess a venom gland; they form a hypothetical clade, Toxicofera, containing the suborders Serpentes and Iguania and the families Varanidae, Anguidae, and Helodermatidae.{{cite journal |date=February 2006 |title=Early evolution of the venom system in lizards and snakes |journal=Nature |volume=439 |pages=584–588 |doi=10.1038/nature04328 |pmid=16292255 |last1=Fry |first1=B. G. |author2=Vidal, N. |author3=Norman, J. A. |author4=Vonk, F. J. |author5=Scheib, H. |author6=Ramjan, S. F. |author7=Kuruppu, S. |author8=Fung, K. |author9=Hedges, S. B. |author10=Richardson, M. K. |author11=Hodgson, W. C. |author12=Ignjatovic, V. |author13=Summerhayes, R. |author14=Kochva, E. |display-authors=3 |issue=7076 |bibcode=2006Natur.439..584F |s2cid=4386245 }}

{{Main|Venomous mammal}}

Euchambersia, an extinct genus of therocephalians, is hypothesized to have had venom glands attached to its canine teeth.{{cite journal |last1=Benoit |first1=J. |last2=Norton |first2=L. A. |last3=Manger |first3=P. R. |last4=Rubidge |first4=B. S. |title=Reappraisal of the envenoming capacity of Euchambersia mirabilis (Therapsida, Therocephalia) using μCT-scanning techniques |date=2017 |journal=PLOS ONE |volume=12 |issue=2 |page=e0172047 |doi=10.1371/journal.pone.0172047 |pmid=28187210 |pmc=5302418 |bibcode=2017PLoSO..1272047B |doi-access=free }}

A few species of living mammals are venomous, including solenodons, shrews, the European mole, vampire bats, male platypuses, and slow lorises.{{Cite journal |last1=Nekaris |first1=K. Anne-Isola |last2=Moore |first2=Richard S. |last3=Rode |first3=E. Johanna |last4=Fry |first4=Bryan G. |date=2013-09-27 |title=Mad, bad and dangerous to know: the biochemistry, ecology and evolution of slow loris venom |journal=Journal of Venomous Animals and Toxins Including Tropical Diseases |volume=19 |issue=1 |page=21 |doi=10.1186/1678-9199-19-21|pmid=24074353 |pmc=3852360 |doi-access=free }} Shrews have venomous saliva and most likely evolved their trait similarly to snakes.{{cite journal |last1=Ligabue-Braun |first1=R. |author2=Verli, H. |author3=Carlini, C. R. |year=2012 |title=Venomous mammals: a review |journal=Toxicon |volume=59 |issue=7–8 |pages=680–695 |doi=10.1016/j.toxicon.2012.02.012|pmid=22410495 |bibcode=2012Txcn...59..680L }} The presence of tarsal spurs akin to those of the platypus in many non-therian Mammaliaformes groups suggests that venom was an ancestral characteristic among mammals.Jørn H. Hurum, Zhe-Xi Luo, and Zofia Kielan-Jaworowska, Were mammals originally venomous?, Acta Palaeontologica Polonica 51 (1), 2006: 1-11

Extensive research on platypuses shows that their toxin was initially formed from gene duplication, but data provides evidence that the further evolution of platypus venom does not rely as much on gene duplication as was once thought.{{cite journal |last1=Wong |first1=E. S. |last2=Belov |first2=K. |year=2012 |title=Venom evolution through gene duplications |journal=Gene |volume=496 |issue=1 |pages=1–7 |doi= 10.1016/j.gene.2012.01.009 |pmid=22285376 }} Modified sweat glands are what evolved into platypus venom glands. Although it is proven that reptile and platypus venom have independently evolved, it is thought that there are certain protein structures that are favored to evolve into toxic molecules. This provides more evidence of why venom has become a homoplastic trait and why very different animals have convergently evolved.

Envenomation resulted in 57,000 human deaths in 2013, down from 76,000 deaths in 1990.{{cite journal |author=((GBD 2013 Mortality and Causes of Death Collaborators)) |title=Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013 |journal=Lancet |date=17 December 2014 |pmid=25530442 |doi=10.1016/S0140-6736(14)61682-2 |pmc=4340604 |volume=385 |issue=9963 |pages=117–171}} Venoms, found in over 173,000 species, have potential to treat a wide range of diseases, explored in over 5,000 scientific papers.{{cite magazine |last1=Mullin |first1=Emily |title=Animal Venom Database Could Be Boon To Drug Development |url=https://www.forbes.com/sites/emilymullin/2015/11/29/animal-venom-database-could-be-boon-to-drug-development/#4fa4e53c7992 |magazine=Forbes |access-date=30 September 2018 |date=29 November 2015}}

In medicine, snake venom proteins are used to treat conditions including thrombosis, arthritis, and some cancers.{{cite journal |last1=Pal |first1=S. K. |last2=Gomes |first2=A. |last3=Dasgupta |first3=S. C. |last4=Gomes |first4=A. |title=Snake venom as therapeutic agents: from toxin to drug development. |journal=Indian Journal of Experimental Biology |volume=40 |issue=12 |year=2002 |pmid=12974396 |pages=1353–1358}}{{cite magazine |last1=Holland |first1=Jennifer S. |title=The Bite That Heals |url=https://www.nationalgeographic.com/magazine/2013/02/venom/ |archive-url=https://web.archive.org/web/20180525062346/https://www.nationalgeographic.com/magazine/2013/02/venom/ |url-status=dead |archive-date=25 May 2018 |magazine=National Geographic |access-date=30 September 2018 |date=February 2013}} Gila monster venom contains exenatide, used to treat type 2 diabetes. Solenopsins extracted from fire ant venom has demonstrated biomedical applications, ranging from cancer treatment to psoriasis.{{Cite journal |last1=Fox |first1=Eduardo G.P. |last2=Xu |first2=Meng |last3=Wang |first3=Lei |last4=Chen |first4=Li |last5=Lu |first5=Yong-Yue |date=May 2018 |title=Speedy milking of fresh venom from aculeate hymenopterans |journal=Toxicon |volume=146 |pages=120–123 |doi=10.1016/j.toxicon.2018.02.050 |pmid=29510162|bibcode=2018Txcn..146..120F }}{{cite book |last=Fox |first=Eduardo Gonçalves Paterson |chapter=Venom Toxins of Fire Ants |date=2021 |title=Venom Genomics and Proteomics |pages=149–167 |editor-last=Gopalakrishnakone |editor-first=P. |editor-first2=Juan J. |editor-last2=Calvete |publisher=Springer Netherlands |doi=10.1007/978-94-007-6416-3_38 |isbn=9789400766495 |chapter-url=https://link.springer.com/referenceworkentry/10.1007/978-94-007-6649-5_38-1}} A branch of science, venomics, has been established to study the proteins associated with venom and how individual components of venom can be used for pharmaceutical means.{{Cite journal |last=Calvete |first=Juan J. |date=December 2013 |title=Snake venomics: From the inventory of toxins to biology |journal=Toxicon |volume=75 |pages=44–62 |doi=10.1016/j.toxicon.2013.03.020 |pmid=23578513 |bibcode=2013Txcn...75...44C |issn=0041-0101}}

{{Further|Antipredator adaptations}}

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|footer = The California ground squirrel is resistant to the Northern Pacific rattlesnake's powerful venom.

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Venom is used as a trophic weapon by many predator species. The coevolution between predators and prey is the driving force of venom resistance, which has evolved multiple times throughout the animal kingdom.{{Cite journal |last1=Arbuckle |first1=Kevin |last2=Rodríguez de la Vega |first2=Ricardo C. |last3=Casewell |first3=Nicholas R. |date=December 2017 |title=Coevolution takes the sting out of it: Evolutionary biology and mechanisms of toxin resistance in animals |journal=Toxicon |volume=140 |pages=118–131 |doi=10.1016/j.toxicon.2017.10.026 |pmid=29111116 |bibcode=2017Txcn..140..118A |s2cid=11196041 |url=https://archive.lstmed.ac.uk/7837/1/Coevolution%20takes%20the%20sting%20out%20of%20it%20.pdf}} The coevolution between venomous predators and venom-resistant prey has been described as a chemical arms race.{{Cite journal |last1=Dawkins |first1=Richard |last2=Krebs |first2=John Richard |last3= Maynard Smith |first3=J. |last4=Holliday |first4=Robin |date=1979-09-21 |title=Arms races between and within species |journal=Proceedings of the Royal Society of London. Series B. Biological Sciences |volume=205 |issue=1161 |pages=489–511 |doi=10.1098/rspb.1979.0081 |pmid=42057 |bibcode= 1979RSPSB.205..489D |s2cid=9695900}} Predator/prey pairs are expected to coevolve over long periods of time.{{cite book |last1=McCabe |first1=Thomas M. |last2=Mackessy |first2=Stephen P. |title=Evolution of Resistance to Toxins in Prey |date=2015 |work=Evolution of Venomous Animals and Their Toxins |pages=1–19 |editor-last=Gopalakrishnakone |editor-first=P. |series=Toxinology |publisher=Springer Netherlands |doi= 10.1007/978-94-007-6727-0_6-1 |isbn=978-94-007-6727-0 |editor2-last=Malhotra |editor2-first=Anita}} As the predator capitalizes on susceptible individuals, the surviving individuals are limited to those able to evade predation.{{Cite journal |last1=Nuismer |first1=Scott L. |last2=Ridenhour |first2=Benjamin J. |last3=Oswald |first3=Benjamin P. |date=2007 |title=Antagonistic Coevolution Mediated by Phenotypic Differences Between Quantitative Traits |journal=Evolution |volume=61 |issue=8 |pages=1823–1834 |doi=10.1111/j.1558-5646.2007.00158.x |pmid=17683426 |s2cid=24103 |doi-access=free }} Resistance typically increases over time as the predator becomes increasingly unable to subdue resistant prey.{{Cite journal |last1=Holding |first1=Matthew L. |last2=Drabeck |first2=Danielle H. |last3= Jansa |first3=Sharon A. |last4=Gibbs |first4=H. Lisle |date=1 November 2016 |title=Venom Resistance as a Model for Understanding the Molecular Basis of Complex Coevolutionary Adaptations |url=https://academic.oup.com/icb/article/56/5/1032/2420622 |journal=Integrative and Comparative Biology |volume=56 |issue=5 |pages=1032–1043 |doi=10.1093/icb/icw082 |pmid=27444525 |issn=1540-7063 |doi-access=free}} The cost of developing venom resistance is high for both predator and prey.{{Cite journal |last=Calvete |first=Juan J. |date=1 March 2017 |title=Venomics: integrative venom proteomics and beyond |journal=Biochemical Journal |volume=474 |issue=5 |pages=611–634 |doi=10.1042/BCJ20160577 |pmid=28219972 |issn=0264-6021 |doi-access= }} The payoff for the cost of physiological resistance is an increased chance of survival for prey, but it allows predators to expand into underutilised trophic niches.{{Cite journal |last1=Morgenstern |first1=David |last2=King |first2=Glenn F. |date=1 March 2013 |title=The venom optimization hypothesis revisited |journal=Toxicon |volume=63 |pages=120–128 |doi=10.1016/j.toxicon.2012.11.022 |pmid=23266311 |bibcode=2013Txcn...63..120M }}

The California ground squirrel has varying degrees of resistance to the venom of the Northern Pacific rattlesnake.{{Cite journal |last1=Poran |first1=Naomie S. |last2=Coss |first2=Richard G. |last3=Benjamini |first3=Eli |date=1987-01-01 |title=Resistance of California ground squirrels (Spermophilus Beecheyi) to the venom of the northern Pacific rattlesnake (Crotalus Viridis Oreganus): A study of adaptive variation |journal=Toxicon |volume=25 |issue=7 |pages=767–777 |doi=10.1016/0041-0101(87)90127-9 |pmid=3672545 |bibcode=1987Txcn...25..767P |issn=0041-0101}} The resistance involves toxin scavenging and depends on the population. Where rattlesnake populations are denser, squirrel resistance is higher.{{Cite journal |last1=Coss |first1=Richard G. |last2=Poran |first2=Naomie S. |last3=Gusé |first3=Kevin L. |last4=Smith |first4=David G. |date=1993-01-01 |title=Development of Antisnake Defenses in California Ground Squirrels (Spermophilus Beecheyi): II. Microevolutionary Effects of Relaxed Selection From Rattlesnakes |journal=Behaviour |volume=124 |issue=1–2 |pages=137–162 |doi=10.1163/156853993X00542 |issn=0005-7959}} Rattlesnakes have responded locally by increasing the effectiveness of their venom.{{Cite journal |last1=Holding |first1=Matthew L. |last2=Biardi |first2=James E. |last3=Gibbs |first3=H. Lisle |date=2016-04-27 |title=Coevolution of venom function and venom resistance in a rattlesnake predator and its squirrel prey |journal=Proceedings of the Royal Society B: Biological Sciences |volume=283 |issue=1829 |pages=20152841 |doi=10.1098/rspb.2015.2841 |pmc=4855376 |pmid=27122552}}

The kingsnakes of the Americas are constrictors that prey on many venomous snakes.{{Cite book |url=https://archive.org/details/fieldguidetorept0000cona |title=A field guide to reptiles and amphibians of Eastern and Central North America. |last=Conant |first=Roger |date=1975 |publisher=Houghton Mifflin |isbn=0-395-19979-4 |edition=Second |location=Boston |oclc=1423604 |url-access=registration }} They have evolved resistance which does not vary with age or exposure. They are immune to the venom of snakes in their immediate environment, like copperheads, cottonmouths, and North American rattlesnakes, but not to the venom of, for example, king cobras or black mambas.{{Cite journal |last1=Weinstein |first1=Scott A. |last2=DeWitt |first2=Clement F. |last3=Smith |first3=Leonard A. |date=December 1992 |title=Variability of Venom-Neutralizing Properties of Serum from Snakes of the Colubrid Genus Lampropeltis |journal=Journal of Herpetology |volume=26 |issue=4 |pages=452 |doi=10.2307/1565123 |jstor=1565123 |s2cid=53706054 }}

File:Ocellaris clownfish, Flickr.jpg always live among venomous sea anemone tentacles and are resistant to the venom.]]

Among marine animals, eels are resistant to sea snake venoms, which contain complex mixtures of neurotoxins, myotoxins, and nephrotoxins, varying according to species.{{Cite journal |last1=Heatwole |first1=Harold |last2=Poran |first2=Naomie S. |date=1995-02-15 |title=Resistances of Sympatric and Allopatric Eels to Sea Snake Venoms |journal=Copeia |volume=1995 |issue=1 |pages=136 |doi=10.2307/1446808 |jstor=1446808}}{{Cite journal |last1=Heatwole |first1=Harold |last2=Powell |first2=Judy |date=May 1998 |title=Resistance of eels (Gymnothorax) to the venom of sea kraits (Laticauda colubrina): a test of coevolution |journal=Toxicon |volume=36 |issue=4 |pages=619–625 |doi=10.1016/S0041-0101(97)00081-0 |pmid=9643474|bibcode=1998Txcn...36..619H }} Eels are especially resistant to the venom of sea snakes that specialise in feeding on them, implying coevolution; non-prey fishes have little resistance to sea snake venom.{{Cite journal |last1=Zimmerman |first1=K. D. |last2=Heatwole |first2=Harold |last3=Davies |first3=H. I. |date=1992-03-01 |title=Survival times and resistance to sea snake (Aipysurus laevis) venom by five species of prey fish |journal=Toxicon |volume=30 |issue=3 |pages=259–264 |doi=10.1016/0041-0101(92)90868-6 |pmid=1529461 |bibcode=1992Txcn...30..259Z |issn=0041-0101}}

Clownfish always live among the tentacles of venomous sea anemones (an obligatory symbiosis for the fish),{{Cite journal |last1=Litsios |first1=Glenn |last2=Sims |first2=Carrie A. |last3=Wüest |first3=Rafael O. |last4=Pearman |first4=Peter B. |last5=Zimmermann |first5=Niklaus E. |last6=Salamin |first6=Nicolas |date=2012-11-02 |title=Mutualism with sea anemones triggered the adaptive radiation of clownfishes |journal=BMC Evolutionary Biology |volume=12 |issue=1 |pages=212 |doi=10.1186/1471-2148-12-212 |issn=1471-2148 |pmc=3532366 |pmid=23122007 |doi-access=free |bibcode=2012BMCEE..12..212L }} and are resistant to their venom.{{Cite journal |last=Fautin |first=Daphne G. |date=1991 |title=The anemonefish symbiosis: what is known and what is not |journal=Symbiosis |volume=10 |pages=23–46 |url=https://kuscholarworks.ku.edu/handle/1808/6134 |via=University of Kansas}}{{Cite journal |last=Mebs |first=Dietrich |date=2009-12-15 |title=Chemical biology of the mutualistic relationships of sea anemones with fish and crustaceans |journal=Toxicon |series=Cnidarian Toxins and Venoms |volume=54 |issue=8 |pages=1071–1074 |doi=10.1016/j.toxicon.2009.02.027 |pmid=19268681 |bibcode=2009Txcn...54.1071M |issn=0041-0101}} Only 10 known species of anemones are hosts to clownfish and only certain pairs of anemones and clownfish are compatible.{{Citation |last1=da Silva |first1=Karen Burke |title=Sea Anemones and Anemonefish: A Match Made in Heaven |date=2016 |work=The Cnidaria, Past, Present and Future: The world of Medusa and her sisters |pages=425–438 |editor-last=Goffredo |editor-first=Stefano |publisher=Springer International Publishing |doi=10.1007/978-3-319-31305-4_27 |isbn=978-3-319-31305-4 |last2=Nedosyko |first2=Anita |editor2-last=Dubinsky |editor2-first=Zvy}}{{Cite journal |last1=Nedosyko |first1=Anita M. |last2=Young |first2=Jeanne E. |last3=Edwards |first3=John W. |last4=Silva |first4=Karen Burke da |date=2014-05-30 |title=Searching for a Toxic Key to Unlock the Mystery of Anemonefish and Anemone Symbiosis |journal=PLOS ONE |volume=9 |issue=5 |pages=e98449 |doi=10.1371/journal.pone.0098449 |issn=1932-6203 |pmc=4039484 |pmid=24878777 |bibcode=2014PLoSO...998449N |doi-access=free}} All sea anemones produce venoms delivered through discharging nematocysts and mucous secretions. The toxins are composed of peptides and proteins. They are used to acquire prey and to deter predators by causing pain, loss of muscular coordination, and tissue damage. Clownfish have a protective mucus that acts as a chemical camouflage or macromolecular mimicry preventing "not self" recognition by the sea anemone and nematocyst discharge.{{Cite journal |last=Mebs |first=D. |date=1994-09-01 |title=Anemonefish symbiosis: Vulnerability and resistance of fish to the toxin of the sea anemone |journal=Toxicon |volume=32 |issue=9 |pages=1059–1068 |doi=10.1016/0041-0101(94)90390-5 |pmid=7801342 |bibcode=1994Txcn...32.1059M |issn=0041-0101}}{{Cite journal |last1=Lubbock |first1=R. |last2=Smith |first2=David Cecil |date=1980-02-13 |title=Why are clownfishes not stung by sea anemones? |journal=Proceedings of the Royal Society of London. Series B. Biological Sciences |volume=207 |issue=1166 |pages=35–61 |doi=10.1098/rspb.1980.0013 |bibcode=1980RSPSB.207...35L |s2cid=86114704}}{{Cite journal |last1=Litsios |first1=Glenn |last2=Kostikova |first2=Anna |last3=Salamin |first3=Nicolas |date=2014-11-22 |title=Host specialist clownfishes are environmental niche generalists |journal=Proceedings of the Royal Society B: Biological Sciences |volume=281 |issue=1795 |pages=20133220 |doi=10.1098/rspb.2013.3220 |pmc=4213602 |pmid=25274370}} Clownfish may acclimate their mucus to resemble that of a specific species of sea anemone.

Venoms in the sense of actively delivered toxins are not restricted to animals; all domains and kingdoms of life have evolved some version of a "venom".{{cite web |last1=Lomte |first1=Tarun Sai |title=Venom is everywhere: Study examines hidden toxin delivery systems across life forms |url=https://www.news-medical.net/news/20250223/Venom-is-everywhere-Study-examines-hidden-toxin-delivery-systems-across-life-forms.aspx |website=News-Medical |language=en |date=23 February 2025}}{{cite journal |last1=Hayes |first1=William K. |last2=Gren |first2=Eric C. K. |last3=Nelsen |first3=David R. |last4=Corbit |first4=Aaron G. |last5=Cooper |first5=Allen M. |last6=Fox |first6=Gerad A. |last7=Streit |first7=M. Benjamin |title=It's a Small World After All: The Remarkable but Overlooked Diversity of Venomous Organisms, with Candidates Among Plants, Fungi, Protists, Bacteria, and Viruses |journal=Toxins |date=20 February 2025 |volume=17 |issue=3 |pages=99 |doi=10.3390/toxins17030099|doi-access=free |pmc=11945383 }}

• Bacteria have the relatively well-known secretion systems that can inject a payload (possibly a toxin) into another cell. Pseudomonas aeruginosa, for example, use a type VI secretion system to target competing microbes.
• The injection mechanism of bacteriophages is arguably similar to a venom.
• Plants have stinging hairs that deliver toxins into targets. There are also more active mechanisms such as the haustorium of Cuscuta, injecting digestive enzymes to facilitate extration of nutrients.
• Phytopathogenic fungi use appressoria to penetrate target plants and deliver cell-killing toxins. Entomopathogenic fungi may also use appressoria to penetrate insects.
• Nematophagous fungi use many mechanisms to capture and penetrate the target nematode. They also produce toxins.
• Among protists, Coleps use specialized organelles called toxicysts to inject toxins into prey. Other protists may use extrusomes.

• Schmidt Sting Pain Index

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