Evolution of snake venom
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Venom in snakes and some lizards is a form of saliva that has been modified into venom over its evolutionary history.[1] In snakes, venom has evolved to kill or subdue prey, as well as to perform other diet-related functions.[2] While snakes occasionally use their venom in self defense, this is not believed to have had a strong effect on venom evolution.[3] The evolution of venom is thought to be responsible for the enormous expansion of snakes across the globe.[4][5][6]
The evolutionary history of snake venom is a matter of debate. Historically, snake venom was believed to have evolved once, at the base of the
Snake venom evolution is thought to be driven by an evolutionary arms race between venom proteins and prey physiology.[13] The common mechanism of evolution is thought to be gene duplication followed by natural selection for adaptive traits.[14] The adaptations produced by this process include venom more toxic to specific prey in several lineages,[15][16][17] proteins that pre-digest prey,[18] and a method to track down prey after a bite.[19] These various adaptations of venom have also led to considerable debate about the definition of venom and venomous snakes.[20] Changes in the diet of a lineage have been linked to atrophication of the venom.[8][9]
Evolutionary history
The origin of venom is thought to have provided the catalyst for the rapid diversification of snakes in the
Serpentes
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A cladogram adapted from Fry et al. (2012) showing a subset of suggested protein recruitment events. [A]: 13 toxin families, including
Until the use of
The "Toxicoferan hypothesis" was subsequently challenged. A study performed in 2014 found that homologs of 16 venom proteins, which had been used to support the single origin hypothesis, were all expressed at high levels in a number of body tissues.[11] The authors therefore suggested that previous research, which had found venom proteins to be conserved across the supposed Toxicoferan lineage, might have misinterpreted the presence of more generic "housekeeping" genes across this lineage, as a result of only sampling certain tissues within the reptiles' bodies. Therefore, the authors suggested that instead of evolving just once in an ancestral reptile, venom evolved independently in multiple lineages, including once prior to the radiation of the "advanced" snakes.[11] A 2015 study found that homologs of the so-called "toxic" genes were present in numerous tissues of a non-venomous snake, the Burmese python. One of the authors stated that they had found homologs to the venom genes in many tissues outside the oral glands, where venom genes might be expected. This demonstrated the weaknesses of only analyzing transcriptomes (the total messenger RNA in a cell).[10] The team suggested that pythons represented a period in snake evolution before major venom development. The researchers also found that the expansion of venom gene families occurred mostly in highly venomous caenophidian snakes (also referred to as "colubrid snakes"), thus suggesting that most venom evolution took place after this lineage diverged from other snakes.[10] The debate over the Toxicoferan hypothesis is driven in part by disagreement over the definition of a venom.[10][31] As of 2022, the Toxicoferan hypothesis remains a prevalent view.[32]
Mechanisms of evolution
The primary mechanism for the diversification of venom is thought to be the duplication of gene coding for other tissues, followed by their expression in the venom glands. The proteins then evolved into various venom proteins through natural selection. This process, known as the birth-and-death model, is responsible for several of the protein recruitment events in snake venom.[33][13] These duplications occurred in a variety of tissue types with a number of ancestral functions. Notable examples include 3FTx, ancestrally a neurotransmitter found in the brain, which has adapted into a neurotoxin that binds and blocks acetylcholine receptors. Another example is phospholipase A2 (PLA2) type IIA, ancestrally involved with inflammatory processes in normal tissue, which has evolved into venom capable of triggering lipase activity and tissue destruction.[21] The change in function of PLA2, in particular, has been well documented; there is evidence of several separate gene duplication events, often associated with the origin of new snake species.[34] Non-allelic homologous recombination induced by transposon invasion (or recombination between DNA sequences that are similar, but not alleles) has been proposed as the mechanism of duplication of PLA2 genes in rattlesnakes, as an explanation for its rapid evolution.[35] These venom proteins have also occasionally been recruited back into tissue genes.[36]
Gene duplication is not the only way that venom has become more diverse. There have been instances of new venom proteins generated by
Protein recruitment events have occurred at different points in the evolutionary history of snakes. For example, the 3FTX protein family is absent in the viperid lineage, suggesting that it was recruited into snake venom after the viperid snakes branched off from the remaining colubroidae.[38] PLA2 is thought to have been recruited at least two separate times into snake venom, once in elapids and once in viperids, displaying convergent evolution of this protein into a toxin.[39][40] A 2019 study suggested that gene duplication could have allowed different toxins to evolve independently, allowing snakes to experiment with their venom profiles and explore new and effective venom formulations.[40] This was proposed as one of the ways snakes have diversified their venom formulations through millions of years of evolution.[40] The various recruitment events had resulted in snake venom evolving into a very complex mixture of proteins. The venom of rattlesnakes, for example, includes nearly 40 different proteins from different protein families,[41] and other snake venoms have been found to contain more than 100 distinct proteins.[22] The composition of this mixture has been shown to vary geographically, and to be related to the prey species available in a certain region.[17] Snake venom has generally evolved very quickly, with changes occurring faster in the venom than in the rest of the organism.[42]
Selection pressure
Long-standing hypotheses of snake venom evolution have assumed that most snakes inject far more venom into their prey than is required to kill them; thus, venom composition would not be subject to natural selection. This is known as the "overkill" hypothesis.
The genes that code for venom proteins in some snake genera have a proportion of
Several studies have found evidence that venom and resistance to venom in prey species have evolved in a
Besides diet, there are other possible pressures on snake venom composition. A 2019 study found that larger body mass and smaller ecological habitats were correlated with increased venom yield.
In contrast to venom composition and toxicity to specific lineages, venom yield, or the quantity of venom produced by an individual snake, has not been found to vary with the body-mass of prey animals, and instead to vary with the body-mass of snakes producing it. Yield increases with snake body-mass in a consistent with the hypothesis that snakes invest a constant proportion of metabolic output into producing venom, which is metabolically costly.[47]
Functional adaptations
Snakes use their venom to kill or subdue prey, as well as for other diet-related functions, such as digestion. Current scientific theory suggests that snake venom is not used for defense or for competition between members of the same species, unlike in other taxa. Thus adaptive evolution in snake venom has resulted in several adaptations with respect to these diet-related functions that increase the fitness of the snakes that carry them.[58][43][17] This is also reflected in variation in venom composition within a species; venom is known to vary geographically, and by age and size, likely reflecting variation in the prey consumed by different groups within a species.[13] Geographic variation is also present at the species level; island snakes tend to have less complex venoms, while those living in highly productive habitats have more complex venoms, suggesting a biogeographic pattern.[59]
Prey-specific venom toxicity
Venom that is toxic only to a certain taxon, or strongly toxic only to a certain taxon, has been found in a number of snakes, suggesting that these venoms have evolved via natural selection to subdue preferred prey species. Examples of this phenomenon have been found in the Mangrove snake
The natural diets of snakes in the widespread
A 2009 study of the venom of four
Pre-digestion of prey
The various subspecies of the rattlesnake genus
Metalloproteinase activity causes
Tracking bitten prey
Another example of an adaptive function other than prey immobilization is the role of
Diet-based atrophication
Venom in a number of lineages of snakes is thought to have atrophied in response to dietary shifts.
References
Citations
- ^ Hargreaves et al. (a) 2014.
- ^ Casewell et al. 2013, pp. 218–220.
- ^ a b Ward-Smith et al. 2020.
- ^ Fry et al. 2012a, pp. 441–442.
- ^ a b Wuster et al. 2008.
- ^ Lomonte et al. (a) 2014, p. 326.
- ^ a b c d e f Fry et al. 2012a, pp. 434–436.
- ^ a b Fry et al. 2012a, pp. 424–436.
- ^ a b Casewell et al. 2013, pp. 224–227.
- ^ a b c d e f Reyes-Velasco et al. 2015.
- ^ a b c Hargreaves et al. (b) 2014, pp. 153–155.
- ^ a b Xie et al. 2022.
- ^ a b c d e Casewell et al. 2020, pp. 570–581.
- ^ Casewell et al. 2013, pp. 222–223.
- ^ Barlow et al. 2009, pp. 2447–2448.
- ^ a b Calvete et al. 2012, pp. 4094–4098.
- ^ a b c d e f Li et al. 2005.
- ^ a b c d e Mackessy 2010.
- ^ a b c Saviola et al. 2013.
- ^ a b Fry et al. 2012a, p. 443.
- ^ a b Fry et al. 2012a.
- ^ a b Lomonte et al. (a) 2014, pp. 326–327.
- ^ Mackessy 2010, p. 1464.
- ^ Casewell et al. 2013, pp. 225–227.
- ^ Palci et al. 2021.
- ^ Fry et al. 2012a, p. 435.
- ^ a b Almeida et al. 2021.
- ^ a b Sunagar & Abraham 2021.
- ^ Fry & Wuster 2004, p. 870.
- ^ Mount & Brown 2022, pp. 973–985.
- ^ Hargreaves et al. (b) 2014.
- ^ Rao et al. 2022.
- ^ Casewell et al. 2013, p. 223.
- ^ a b c Lynch 2007.
- ^ a b Dowell et al. 2016.
- ^ a b Casewell et al. 2013, p. 223–224.
- ^ Casewell et al. 2011.
- ^ Fry & Wuster 2004, p. 871.
- ^ Fry et al. 2012b.
- ^ a b c Mikheyev & Barua 2019.
- ^ a b c d e f g Gibbs & Mackessy 2009.
- ^ Lomonte et al. (a) 2014, p. 334.
- ^ a b c d Barlow et al. 2009, p. 2443.
- ^ a b Barlow et al. 2009, p. 2447.
- ^ Casewell et al. 2013, p. 220.
- ^ Gibbs & Rossiter 2008.
- ^ a b c Healy, Carbone & Jackson, pp. 527–537.
- ^ a b Casewell et al. 2013, pp. 220–221.
- ^ Lomonte et al. (b) 2014, pp. 112–114.
- ^ Heatwole & Poran 1995.
- ^ Biardi, Chien & Coss 2005.
- ^ Biardi & Coss 2011.
- ^ Pomento et al. 2016.
- ^ Sanz et al. 2006, pp. 2098–2099.
- ^ Zancolli et al. 2019.
- ^ Bohlen 2011.
- ^ Kazandjian et al. 2021.
- ^ Casewell et al. 2013, pp. 219–220.
- ^ Siqueira‐Silva et al. 2021, pp. 1978–1989.
- ^ Modahl et al. 2018.
- ^ Barlow et al. 2009, pp. 2444, 2447.
- ^ a b Barlow et al. 2009, pp. 2446–2448.
- ^ Casewell et al. 2013, pp. 223–225.
- ^ Richards et al. 2012.
- ^ Calvete et al. 2012, pp. 4092–4093.
- ^ Calvete et al. 2012, pp. 4097–4098.
- ^ Fry et al. 2008.
Cited sources
- Almeida, Diego Dantas; Viala, Vincent Louis; Nachtigall, Pedro Gabriel; Broe, Michael; Gibbs, H. Lisle; Serrano, Solange Maria de Toledo; Moura-da-Silva, Ana Maria; Ho, Paulo Lee; Nishiyama-Jr, Milton Yutaka; Junqueira-de-Azevedo, Inácio L. M. (10 May 2021). "Tracking the recruitment and evolution of snake toxins using the evolutionary context provided by the Bothrops jararaca genome". Proceedings of the National Academy of Sciences. 118 (20). PMID 33972420.
- Barlow, A.; Pook, C.E.; Harrison, R.A.; Wuster, E.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. PMID 19364745.
- Biardi, James E.; Chien, David C.; Coss, Richard G. (2005). "California ground squirrel (Spermophilus beecheyi) defenses against rattlesnake venom digestive and hemostatic toxins". Journal of Chemical Ecology. 31 (11): 2501–2518. S2CID 23238627.
- Biardi, JE; Coss, RG (2011). "Rock squirrel (Spermophilus variegatus) blood sera affects proteolytic and hemolytic activities of rattlesnake venoms". Toxicon. 57 (2): 323–31. PMID 21184770.
- Bohlen, Christopher J. (17 November 2011). "A heteromeric Texas coral snake toxin targets acid-sensing ion channels to produce pain". Nature. 479 (7373): 414. PMID 22094702.
- Calvete, J.J.; Ghezellou, P.; Paiva, O.; Matainaho, T.; Ghassempour, A.; Goudarzi, H.; Kraus, F.; Sanz, L.; Williams, D.J. (2012). "Snake venomics of two poorly known Hydrophiinae: Comparative proteomics of the venoms of terrestrial Toxicocalamus longissimus and marine Hydrophis cyanocinctus". Journal of Proteomics. 75 (13): 4091–4101. PMID 22643073.
- Casewell, N. R.; Wagstaff, S. C.; Harrison, R. A.; Renjifo, C.; Wuster, W. (4 April 2011). "Domain Loss Facilitates Accelerated Evolution and Neofunctionalization of Duplicate Snake Venom Metalloproteinase Toxin Genes". Molecular Biology and Evolution. 28 (9): 2637–2649. PMID 21478373.
- Casewell, N.R.; Wuster, W.; Vonk, F.J.; Harrison, R.A.; Fry, B.G. (2013). "Complex cocktails: the evolutionary novelty of venoms". Trends in Ecology & Evolution. 28 (4): 219–229. PMID 23219381.
- Casewell, Nicholas R.; Jackson, Timothy N.W.; Laustsen, Andreas H.; Sunagar, Kartik (2020). "Causes and Consequences of Snake Venom Variation". Trends in Pharmacological Sciences. 41 (8). Elsevier BV: 570–581. PMID 32564899.
- Dowell, Noah L.; Giorgianni, Matt W.; Kassner, Victoria A.; Selegue, Jane E.; Sanchez, Elda E.; Carroll, Sean B. (2016). "The Deep Origin and Recent Loss of Venom Toxin Genes in Rattlesnakes". Current Biology. 26 (18): 2434–2445. PMID 27641771.
- Gibbs, H. Lisle; Rossiter, Wayne (6 February 2008). "Rapid Evolution by Positive Selection and Gene Gain and Loss: PLA2 Venom Genes in Closely Related Sistrurus Rattlesnakes with Divergent Diets". Journal of Molecular Evolution. 66 (2): 151–166. S2CID 3733114.
- Fry, B.G.; Casewell, N.R.; Wuster, W.; Vidal, N.; Young, B.; Jackson, T. N. W. (2012). "The structural and functional diversification of the Toxicofera reptile venom system". Toxicon. 60 (4): 434–448. PMID 22446061.
- Fry, Bryan G.; Wuster, Wolfgang (2004). "Assembling an Arsenal: Origin and Evolution of the Snake Venom Proteome Inferred from Phylogenetic Analysis of Toxin Sequences". Molecular Biology and Evolution. 5 (21): 870–883. PMID 15014162.
- Fry, Bryan G.; Scheib, Holger; Junqueira de Azevedo, Inacio de L.M.; Silva, Debora Andrade; Casewell, Nicholas R. (2012). "Novel transcripts in the maxillary venom glands of advanced snakes". Toxicon. 59 (7–8): 696–708. PMID 22465490.
- Fry, Bryan G.; Scheib, Holger; Van Der Weerd, Louise; Young, Bruce; McNaughtan, Judith; Ramjan, S. F. Ryan; Vidal, Nicolas; Poelmann, Robert E.; Norman, Janette A. (2008). "Evolution of an Arsenal". Molecular & Cellular Proteomics. 7 (2): 215–246. PMID 17855442.
- Gibbs, H.L.; Mackessy, S.P. (2009). "Functional basis of a molecular adaptation: Prey-specific toxic effects of venom from Sistrurus rattlesnakes". Toxicon. 53 (6): 672–679. PMID 19673082.
- Hargreaves, Adam D.; Swain, Martin T.; Hegarty, Matthew J.; Logan, Darren W.; Mulley, John F. (1 August 2014). "Restriction and Recruitment—Gene Duplication and the Origin and Evolution of Snake Venom Toxins". Genome Biology and Evolution. 6 (8): 2088–2095. PMID 25079342.
- Hargreaves, Adam D.; Swain, Martin T.; Logan, Darren W.; Mulley, John F. (2014). "Testing the Toxicofera: Comparative transcriptomics casts doubt on the single, early evolution of the reptile venom system" (PDF). Toxicon. 92: 140–156. PMID 25449103.
- Healy, Kevin; Carbone, Chris; Jackson, Andrew L. (7 January 2019). "Snake venom potency and yield are associated with prey-evolution, predator metabolism and habitat structure". Ecology Letters. 22 (3). Wiley: 527–537. S2CID 58637804.
- Heatwole, Harold; Poran, Naomie S. (1995). "Resistances of sympatric and allopatric eels to sea snake venoms". Copeia. 1995 (1): 136–147. JSTOR 1446808.
- Kazandjian, T. D.; Petras, D.; Robinson, S. D.; van Thiel, J.; Greene, H. W.; Arbuckle, K.; Barlow, A.; Carter, D. A.; Wouters, R. M.; Whiteley, G.; Wagstaff, S. C.; Arias, A. S.; Albulescu, L.-O.; Plettenberg Laing, A.; Hall, C.; Heap, A.; Penrhyn-Lowe, S.; McCabe, C. V.; Ainsworth, S.; da Silva, R. R.; Dorrestein, P. C.; Richardson, M. K.; Gutiérrez, J. M.; Calvete, J. J.; Harrison, R. A.; Vetter, I.; Undheim, E. A. B.; Wüster, W.; Casewell, N. R. (2021). "Convergent evolution of pain-inducing defensive venom components in spitting cobras" (PDF). Science. 371 (6527): 386–390. S2CID 231666401.
- Li, M.; Fry, B.G.; Kini, R.M. (2005). "Eggs-only diet: Its implications for the toxin profile changes and ecology of the marbled sea snake (Aipysurus eydouxii)" (PDF). Journal of Molecular Evolution. 60 (1): 81–89. S2CID 17572816. Archived from the original(PDF) on 3 December 2011. Retrieved 19 November 2014.
- Lomonte, B.; Fernandez, J.; Sanz, L.; Angulo, Y.; Sasa, M.; Gutierrez, J. M.; Calvete, J. J. (2014). "Venomous snakes of Costa Rica: Biological and medical implications of their venom proteomic profiles analyzed through the strategy of snake venomics". Journal of Proteomics. 105: 323–339. PMID 24576642.
- Lomonte, B.; Tsai, W. C.; Urena-Diaz, J. M.; Sanz, L.; Mora-Obando, D.; Sanchez, E. E.; Fry, B.G.; Gutierrez, J. M.; Gibbs, H. L.; Sovic, M.G.; Calvete, J.J. (2014). "Venomics of New World pit vipers: Genus-wide comparisons of venom proteomes across Agkistrodon". Journal of Proteomics. 96: 103–116. PMID 24211403.
- Lynch, V.J. (2007). "Inventing an arsenal: adaptive evolution and neofunctionalization of snake venom phospholipase A(2) genes". BMC Evolutionary Biology. 7 (1): 2. PMID 17233905.
- Mackessy, Stephen P. (2010). "Evolutionary trends in venom composition in the Western Rattlesnakes (Crotalus viridis sensu lato): Toxicity vs. tenderizers". Toxicon. 55 (8): 1463–1474. PMID 20227433.
- Palci, Alessandro; LeBlanc, Aaron R. H.; Panagiotopoulou, Olga; Cleuren, Silke G. C.; Mehari Abraha, Hyab; Hutchinson, Mark N.; Evans, Alistair R.; Caldwell, Michael W.; Lee, Michael S. Y. (11 August 2021). "Plicidentine and the repeated origins of snake venom fangs". Proceedings of the Royal Society B: Biological Sciences. 288 (1956). The Royal Society: 20211391. PMID 34375553.
- Mikheyev, Alexander S.; Barua, Agneesh (2019). "Many Options, Few Solutions: Over 60 My Snakes Converged on a Few Optimal Venom Formulations". Molecular Biology and Evolution. 36 (9): 1964–1974. PMID 31220860.
- Modahl, Cassandra M.; Mrinalini, null; Frietze, Seth; Mackessy, Stephen P. (2018). "Adaptive evolution of distinct prey-specific toxin genes in rear-fanged snake venom". Proceedings of the Royal Society B: Biological Sciences. 285 (1884): 20181003. PMID 30068680.
- Mount, Genevieve G; Brown, Jeremy M (22 March 2022). "Comparing Likelihood Ratios to Understand Genome-Wide Variation in Phylogenetic Support". Systematic Biology. 71 (4). Oxford University Press (OUP): 973–985. PMID 35323986.
- Pomento, AM; Perry, BW; Denton, RD; Gibbs, HL; Holding, ML (2016). "No safety in the trees: Local and species-level adaptation of an arboreal squirrel to the venom of sympatric rattlesnakes". Toxicon. 118: 149–55. PMID 27158112.
- Rao, Wei-qiao; Kalogeropoulos, Konstantinos; Allentoft, Morten E; Gopalakrishnan, Shyam; Zhao, Wei-ning; Workman, Christopher T; Knudsen, Cecilie; Jiménez-Mena, Belén; Seneci, Lorenzo; Mousavi-Derazmahalleh, Mahsa; Jenkins, Timothy P; Rivera-de-Torre, Esperanza; Liu, Si-qi; Laustsen, Andreas H (2022). "The rise of genomics in snake venom research: recent advances and future perspectives". GigaScience. 11. Oxford University Press (OUP). PMID 35365832.
- Reyes-Velasco, Jacobo; Card, Daren C.; Andrew, Audra L.; Shaney, Kyle J.; Adams, Richard H.; Schield, Drew R.; Casewell, Nicholas R.; Mackessy, Stephen P.; Castoe, Todd A. (1 January 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. PMID 25338510.
- Richards, D. P.; Barlow, A.; Wüster, W. (1 January 2012). "Venom lethality and diet: Differential responses of natural prey and model organisms to the venom of the saw-scaled vipers (Echis)". Toxicon. 59 (1): 110–116. PMID 22079297.
- Sanz, Libia; Gibbs, H. Lisle; Mackessy, Stephen P.; Calvete, Juan J. (2006). "Venom Proteomes of Closely Related Sistrurus rattlesnakes with Divergent Diets". Journal of Proteome Research. 5 (9): 2098–2112. PMID 16944921.
- Saviola, A.J.; Chiszar, D.; Busch, C.; Mackessy, S.P. (2013). "Molecular basis for prey relocation in viperid snakes". BMC Biology. 11 (1): 20. PMID 23452837.
- Siqueira‐Silva, Tuany; Lima, Luiz Antônio Gonzaga; Chaves‐Silveira, Jônatas; Amado, Talita Ferreira; Naipauer, Julian; Riul, Pablo; Martinez, Pablo Ariel; Sheard, Catherine (27 July 2021). "Ecological and biogeographic processes drive the proteome evolution of snake venom". Global Ecology and Biogeography. 30 (10). Wiley: 1978–1989. S2CID 237649145.
- Sunagar, Kartik; Abraham, Siju V (3 February 2021). "The Curious Case of the "Neurotoxic Skink": Scientific Literature Points to the Absence of Venom in Scincidae". Toxins. 13 (2). MDPI AG: 114. PMID 33546362.
- Wuster, Wolfgang; Peppin, Lindsay; Pook, Catherine E.; Walker, Daniel E. (2008). "A nesting of vipers: Phylogeny and historical biogeography of the Viperidae (Squamata: Serpentes)". Molecular Phylogenetics and Evolution. 49 (2): 445–459. PMID 18804544.
- Ward-Smith, Harry; Arbuckle, Kevin; Naude, Arno; Wüster, Wolfgang (2020). "Fangs for the memories? A survey of pain in snakebite patients does not support a strong role for defense in the evolution of snake venom composition". PMID 32235759.
- Xie, Bing; Dashevsky, Daniel; Rokyta, Darin; Ghezellou, Parviz; Fathinia, Behzad; Shi, Qiong; Richardson, Michael K.; Fry, Bryan G. (7 January 2022). "Dynamic genetic differentiation drives the widespread structural and functional convergent evolution of snake venom proteinaceous toxins". BMC Biology. 20 (1). Springer Science and Business Media LLC: 4. PMID 34996434.
- Zancolli, Giulia; Calvete, Juan J.; Cardwell, Michael D.; Greene, Harry W.; Hayes, William K.; Hegarty, Matthew J.; Herrmann, Hans-Werner; Holycross, Andrew T.; Lannutti, Dominic I.; Mulley, John F.; Sanz, Libia (13 March 2019). "When one phenotype is not enough: divergent evolutionary trajectories govern venom variation in a widespread rattlesnake species". Proceedings of the Royal Society B: Biological Sciences. 286 (1898): 20182735. PMID 30862287.
External links
- Media related to Evolution of snake venom at Wikimedia Commons