{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T22:17:54Z","timestamp":1790201874225,"version":"4.1.0"},"reference-count":148,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2017,8,6]],"date-time":"2017-08-06T00:00:00Z","timestamp":1501977600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>While snake venoms have been the subject of intense study, comparatively little work has been done on lizard venoms. In this study, we have examined the structural and functional diversification of anguimorph lizard venoms and associated toxins, and related these results to dentition and predatory ecology. Venom composition was shown to be highly variable across the 20 species of Heloderma, Lanthanotus, and Varanus included in our study. While kallikrein enzymes were ubiquitous, they were also a particularly multifunctional toxin type, with differential activities on enzyme substrates and also ability to degrade alpha or beta chains of fibrinogen that reflects structural variability. Examination of other toxin types also revealed similar variability in their presence and activity levels. The high level of venom chemistry variation in varanid lizards compared to that of helodermatid lizards suggests that venom may be subject to different selection pressures in these two families. These results not only contribute to our understanding of venom evolution but also reveal anguimorph lizard venoms to be rich sources of novel bioactive molecules with potential as drug design and development lead compounds.<\/jats:p>","DOI":"10.3390\/toxins9080242","type":"journal-article","created":{"date-parts":[[2017,8,9]],"date-time":"2017-08-09T05:10:01Z","timestamp":1502255401000},"page":"242","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Enter the Dragon: The Dynamic and Multifunctional Evolution of Anguimorpha Lizard Venoms"],"prefix":"10.3390","volume":"9","author":[{"given":"Ivan","family":"Koludarov","sequence":"first","affiliation":[{"name":"Venom Evolution Lab, School of Biological Sciences, University of Queensland, St. Lucia QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy NW","family":"Jackson","sequence":"additional","affiliation":[{"name":"Venom Evolution Lab, School of Biological Sciences, University of Queensland, St. Lucia QLD 4072, Australia"},{"name":"Australian Venom Research Unit, School of Biomedical Sciences, Level 2 Medical Building, University of Melbourne, Victoria 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca op den","family":"Brouw","sequence":"additional","affiliation":[{"name":"Venom Evolution Lab, School of Biological Sciences, University of Queensland, St. Lucia QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Dobson","sequence":"additional","affiliation":[{"name":"Venom Evolution Lab, School of Biological Sciences, University of Queensland, St. Lucia QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Dashevsky","sequence":"additional","affiliation":[{"name":"Venom Evolution Lab, School of Biological Sciences, University of Queensland, St. Lucia QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Arbuckle","sequence":"additional","affiliation":[{"name":"Department of Biosciences, College of Science, Swansea University, Swansea SA2 8PP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christofer J.","family":"Clemente","sequence":"additional","affiliation":[{"name":"University of the Sunshine Coast, School of Science and Engineering, Sippy Downs, Queensland 4558, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward J.","family":"Stockdale","sequence":"additional","affiliation":[{"name":"Gradient Scientific and Technical Diving, Rye, Victoria 3941, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9171-5874","authenticated-orcid":false,"given":"Chip","family":"Cochran","sequence":"additional","affiliation":[{"name":"Department of Earth and Biological Sciences, Loma Linda University, Loma Linda, CA 92350, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan","family":"Debono","sequence":"additional","affiliation":[{"name":"Venom Evolution Lab, School of Biological Sciences, University of Queensland, St. Lucia QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carson","family":"Stephens","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Queensland University of Technology, Brisbane QLD 4001, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadya","family":"Panagides","sequence":"additional","affiliation":[{"name":"Venom Evolution Lab, School of Biological Sciences, University of Queensland, St. Lucia QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Li","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, University of Macau, Avenida da Universidade, Taipa, Macau"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary-Louise Roy","family":"Manchadi","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, University of Queenslnd, St. Lucia QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aude","family":"Violette","sequence":"additional","affiliation":[{"name":"Alphabiotoxine Laboratory sprl, Barberie 15, 7911 Montroeul-au-bois, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudy","family":"Fourmy","sequence":"additional","affiliation":[{"name":"Alphabiotoxine Laboratory sprl, Barberie 15, 7911 Montroeul-au-bois, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iwan","family":"Hendrikx","sequence":"additional","affiliation":[{"name":"Venom Evolution Lab, School of Biological Sciences, University of Queensland, St. Lucia QLD 4072, 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Macau"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6661-1283","authenticated-orcid":false,"given":"Bryan G.","family":"Fry","sequence":"additional","affiliation":[{"name":"Venom Evolution Lab, School of Biological Sciences, University of Queensland, St. Lucia QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,8,6]]},"reference":[{"key":"ref_1","unstructured":"Auffenberg, W. (1981). Behavioral Ecology of the Komodo Monitor, University Presses of Florida."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"545","DOI":"10.7589\/0090-3558-38.3.545","article-title":"Aerobic salivary bacteria in wild and captive Komodo dragons","volume":"38","author":"Montgomery","year":"2002","journal-title":"J. Wildl. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1638\/2012-0022R.1","article-title":"Anaerobic and aerobic bacteriology of the saliva and gingiva from 16 captive Komodo dragons (Varanus komodoensis): New implications for the \u201cbacteria as venom\u201d model","volume":"44","author":"Goldstein","year":"2013","journal-title":"J. Zoo Wildl. Med."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Hocknull, S.A., Piper, P.J., van den Bergh, G.D., Due, R.A., Morwood, M.J., and Kurniawan, I. (2009). Dragon\u2019s paradise lost: Palaeobiogeography, evolution and extinction of the largest-ever terrestrial lizards (Varanidae). PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0007241"},{"key":"ref_5","unstructured":"Fry, B.G. (2015). Poisonous snakes and bacteria as a Komodo dragon weapon: Which is a myth and which is reality?. Venomous Reptiles: Evolution, Pathophysiology and Biodiscovery, Oxford University Press."},{"key":"ref_6","unstructured":"Estes, R., and Pregill, G. (1988). Charles L. Camp\u2014An appreciation. Phylogenetic Relationships of the Lizard Families: Essay Commemorating Charles L. Camp, Stanford University Press."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1126\/science.1232455","article-title":"Evolution. Who speaks with a forked tongue?","volume":"338","author":"Losos","year":"2012","journal-title":"Science"},{"key":"ref_8","first-page":"79","article-title":"Monitors, mammals and Wallace\u2019s line","volume":"16","author":"Sweet","year":"2007","journal-title":"Mertensiella"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1655\/HERPETOLOGICA-D-13-00027","article-title":"Walking the Natural-History Trail","volume":"69","author":"Vitt","year":"2013","journal-title":"Herpetologica"},{"key":"ref_10","unstructured":"Conta, M. (2016). Chasing Flamingos: Toxicofera and the Misinterpretation of Venom in Varanid Lizards. Proceedings of the 2015 Interdisciplinary World Conference on Monitor Lizards, Suan Sunandha Rajabhat University."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Hedges, S.B., and Kumar, S. (2009). Lizards, snakes, and amphisbaenians (Squamata). The Timetree of Life, Oxford University Press.","DOI":"10.1093\/oso\/9780199535033.003.0053"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1111\/j.1558-5646.2011.01437.x","article-title":"Extinction, ecological opportunity, and the origins of global snake diversity","volume":"66","author":"Pyron","year":"2012","journal-title":"Evolution"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Pyron, R.A., Burbrink, F.T., and Wiens, J.J. (2013). A phylogeny and revised classification of Squamata, including 4161 species of lizards and snakes. BMC Evol. Biol., 13.","DOI":"10.1186\/1471-2148-13-93"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Reeder, T.W., Townsend, T.M., Mulcahy, D.G., Noonan, B.P., Wood, P.L., Sites, J.W., and Wiens, J.J. (2015). Integrated analyses resolve conflicts over squamate reptile phylogeny and reveal unexpected placements for fossil taxa. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0118199"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1080\/10635150490522340","article-title":"Molecular phylogenetics of squamata: The position of snakes, amphisbaenians, and dibamids, and the root of the squamate tree","volume":"53","author":"Townsend","year":"2004","journal-title":"Syst. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.ympev.2004.01.001","article-title":"New insights into the early history of snakes inferred from two nuclear genes","volume":"31","author":"Vidal","year":"2004","journal-title":"Mol. Phylogenet. Evol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1016\/j.crvi.2005.10.001","article-title":"The phylogeny of squamate reptiles (lizards, snakes, and amphisbaenians) inferred from nine nuclear protein-coding genes","volume":"328","author":"Vidal","year":"2005","journal-title":"C. R. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.crvi.2008.07.010","article-title":"The molecular evolutionary tree of lizards, snakes, and amphisbaenians","volume":"332","author":"Vidal","year":"2009","journal-title":"C. R. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1098\/rsbl.2012.0703","article-title":"Resolving the phylogeny of lizards and snakes (Squamata) with extensive sampling of genes and species","volume":"8","author":"Wiens","year":"2012","journal-title":"Biol. Lett."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1093\/sysbio\/syq048","article-title":"Combining Phylogenomics and Fossils in Higher-Level Squamate Reptile Phylogeny: Molecular Data Change the Placement of Fossil Taxa","volume":"59","author":"Wiens","year":"2010","journal-title":"Syst. Biol."},{"key":"ref_21","first-page":"38","article-title":"Novel Approaches for Phylogenetic Inference from Morphological Data and Total-Evidence Dating in Squamate Reptiles (Lizards, Snakes, and Amphisbaenians)","volume":"66","author":"Pyron","year":"2017","journal-title":"Syst. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.ympev.2015.10.009","article-title":"Combining phylogenomic and supermatrix approaches, and a time-calibrated phylogeny for squamate reptiles (lizards and snakes) based on 52 genes and 4162 species","volume":"94","author":"Zheng","year":"2016","journal-title":"Mol. Phylogenet. Evol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1038\/nature04328","article-title":"Early evolution of the venom system in lizards and snakes","volume":"439","author":"Fry","year":"2006","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1101\/gr.3228405","article-title":"From genome to \u201cvenome\u201d: Molecular origin and evolution of the snake venom proteome inferred from phylogenetic analysis of toxin sequences and related body proteins","volume":"15","author":"Fry","year":"2005","journal-title":"Genome Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/j.toxicon.2012.02.013","article-title":"The structural and functional diversification of the Toxicofera reptile venom system","volume":"60","author":"Fry","year":"2012","journal-title":"Toxicon"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1146\/annurev.genom.9.081307.164356","article-title":"The toxicogenomic multiverse: Convergent recruitment of proteins into animal venoms","volume":"10","author":"Fry","year":"2009","journal-title":"Annu. Rev.Genom. Hum. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1093\/molbev\/msp251","article-title":"Novel venom proteins produced by differential domain-expression strategies in beaded lizards and gila monsters (genus Heloderma)","volume":"27","author":"Fry","year":"2010","journal-title":"Mol. Biol. Evol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1074\/mcp.M700094-MCP200","article-title":"Evolution of an arsenal: Structural and functional diversification of the venom system in the advanced snakes (Caenophidia)","volume":"7","author":"Fry","year":"2008","journal-title":"Mol. Cell. Proteom."},{"key":"ref_29","unstructured":"Fry, B.G. (2015). The origin and evolution of the Toxicofera reptile venom system. Venomous Reptiles and Their Toxins: Evolution, Pathophysiology and Biodiscovery, Oxford University Press."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1074\/mcp.M112.023143","article-title":"Squeezers and leaf-cutters: Differential diversification and degeneration of the venom system in toxicoferan reptiles","volume":"12","author":"Fry","year":"2013","journal-title":"Mol. Cell. Proteom."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.jprot.2009.01.009","article-title":"Evolution and diversification of the Toxicofera reptile venom system","volume":"72","author":"Fry","year":"2009","journal-title":"J. Proteom."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2369","DOI":"10.1074\/mcp.M110.001370","article-title":"Functional and structural diversification of the Anguimorpha lizard venom system","volume":"9","author":"Fry","year":"2010","journal-title":"Mol. Cell. Proteom."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"8969","DOI":"10.1073\/pnas.0810883106","article-title":"A central role for venom in predation by Varanus komodoensis (Komodo Dragon) and the extinct giant Varanus (Megalania) priscus","volume":"106","author":"Fry","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1093\/molbev\/msh091","article-title":"Assembling an arsenal: Origin and evolution of the snake venom proteome inferred from phylogenetic analysis of toxin sequences","volume":"21","author":"Fry","year":"2004","journal-title":"Mol. Biol. Evol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1093\/icb\/icw110","article-title":"Understanding biological roles of venoms among the caenophidia: The importance of rear-fanged snakes","volume":"56","author":"Mackessy","year":"2016","journal-title":"Integr. Comp. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Hsiang, A.Y., Field, D.J., Webster, T.H., Behlke, A.D., Davis, M.B., Racicot, R.A., and Gauthier, J.A. (2015). The origin of snakes: Revealing the ecology, behavior, and evolutionary history of early snakes using genomics, phenomics, and the fossil record. BMC Evol. Biol., 15.","DOI":"10.1186\/s12862-015-0358-5"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1146\/annurev-ecolsys-102710-145051","article-title":"Phylogenetic insights on evolutionarynovelties in lizards and snakes: Sex, birth, bodies, niches, and venom","volume":"42","author":"Sites","year":"2011","journal-title":"Annu. Rev. Ecol. Evolut. Syst."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.toxicon.2015.07.005","article-title":"Snake venoms: A brief treatise on etymology, origins of terminology, and definitions","volume":"103","author":"Weinstein","year":"2015","journal-title":"Toxicon"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1007\/s00435-016-0332-9","article-title":"Endless forms most beautiful: The evolution of ophidian oral glands, including the venom system, and the use of appropriate terminology for homologous structures","volume":"136","author":"Jackson","year":"2017","journal-title":"Zoomorphology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.toxicon.2014.10.004","article-title":"Testing the Toxicofera: Comparative transcriptomics casts doubt on the single, early evolution of the reptile venom system","volume":"92","author":"Hargreaves","year":"2014","journal-title":"Toxicon"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Jackson, T.N., and Fry, B.G. (2016). A Tricky Trait: Applying the Fruits of the \u201cFunction Debate\u201d in the Philosophy of Biology to the \u201cVenom Debate\u201d in the Science of Toxinology. Toxins, 8.","DOI":"10.3390\/toxins8090263"},{"key":"ref_42","unstructured":"Mebs, D. (2002). Venomous and Poisonous Animals: A Handbook for Biologists, Toxicologists and Toxinologists, Physicians and Pharmacists, Medpharm."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Malhotra, A. (2017). A Critique of the Toxicoferan Hypothesis. Evolution of Venomous Animals and Their Toxins, Springer Nature.","DOI":"10.1007\/978-94-007-6458-3"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1016\/j.bbrc.2004.11.171","article-title":"Novel natriuretic peptides from the venom of the inland taipan (Oxyuranus microlepidotus): Isolation, chemical and biological characterisation","volume":"327","author":"Fry","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1007\/BF02431476","article-title":"Purification and properties of a kinin liberating enzyme from venom of Heloderma suspectum","volume":"264","author":"Mebs","year":"1969","journal-title":"Naunyn-Schmiedeberg\u2019s Arch. Pharmakol."},{"key":"ref_46","first-page":"75","article-title":"Concerning the Varanus griseus saliva toxicity","volume":"6","author":"Gorelov","year":"1971","journal-title":"Izy. Akademii Turkmenistan SSR"},{"key":"ref_47","first-page":"78","article-title":"Case of intoxification from a bite of Varanus griseus","volume":"87","author":"Sopyev","year":"1987","journal-title":"Izy. Akademii Turkmenistan SSR"},{"key":"ref_48","first-page":"261","article-title":"Varanus griseus (Desert monitor) toxicity","volume":"32","author":"Ballard","year":"2001","journal-title":"Herpetol. Rev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"444","DOI":"10.3109\/0886022X.2013.868223","article-title":"Monitor lizard bite-induced acute kidney injury\u2014A case report","volume":"36","author":"Vikrant","year":"2014","journal-title":"Ren. Fail."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"740","DOI":"10.3109\/0886022X.2015.1006116","article-title":"Reply to Vikrant and Verma about \u201cMonitor Lizard Envenoming\u201d","volume":"37","author":"White","year":"2015","journal-title":"Ren. Fail."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.wem.2016.02.009","article-title":"Bitten by a Dragon","volume":"27","author":"Ducey","year":"2016","journal-title":"Wilderness Environ. Med."},{"key":"ref_52","first-page":"123","article-title":"The effect of relative prey size on the ingestion behavior of the Bengal monitor, Varanus bengalensis (Sauria: Varanidae)","volume":"30","author":"Loop","year":"1974","journal-title":"Herpetologica"},{"key":"ref_53","first-page":"43","article-title":"Oral glands of the Reptilia","volume":"8","author":"Kochva","year":"1978","journal-title":"Physiology B"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/s00239-004-0138-0","article-title":"Eggs-Only diet: Its implications for the toxin profile changes and ecology of the marbled sea snake (Aipysurus eydouxii)","volume":"60","author":"Li","year":"2005","journal-title":"J. Mol. Evol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1093\/molbev\/msi077","article-title":"Putting the brakes on snake venom evolution: The unique molecular evolutionary patterns of Aipysuras eydouxii (Marbled sea snake) phospholipase A(2) toxins","volume":"22","author":"Li","year":"2005","journal-title":"Mol. Biol. Evol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.toxicon.2012.11.022","article-title":"The venom optimization hypothesis revisited","volume":"63","author":"Morgenstern","year":"2013","journal-title":"Toxicon"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3582","DOI":"10.3390\/toxins6123582","article-title":"Fossilized venom: The unusually conserved venom profiles of Heloderma species (beaded lizards and gila monsters)","volume":"6","author":"Koludarov","year":"2014","journal-title":"Toxins"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.toxicon.2010.12.016","article-title":"The development of Byetta (exenatide) from the venom of the Gila monster as an anti-diabetic agent","volume":"59","author":"Furman","year":"2012","journal-title":"Toxicon"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.ygcen.2011.11.025","article-title":"Origin and convergent evolution of exendin genes","volume":"175","author":"Irwin","year":"2012","journal-title":"Gen. Comp. Endocrinol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.peptides.2007.10.025","article-title":"Helokinestatin: A new bradykinin B-2 receptor antagonist decapeptide from lizard venom","volume":"29","author":"Kwok","year":"2008","journal-title":"Peptides"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jprot.2015.01.004","article-title":"Characterization of the gila monster (Heloderma suspectum suspectum) venom proteome","volume":"117","author":"Sanggaard","year":"2015","journal-title":"J. Proteom."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1016\/j.peptides.2011.03.012","article-title":"The natriuretic peptide\/helokinestatin precursor from Mexican beaded lizard (Heloderma horridum) venom: Amino acid sequence deduced from cloned cDNA and identification of two novel encoded helokinestatins","volume":"32","author":"Ma","year":"2011","journal-title":"Peptides"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.peptides.2012.03.010","article-title":"Helokinestatin-7 peptides from the venoms of Heloderma lizards","volume":"35","author":"Ma","year":"2012","journal-title":"Peptides"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1016\/j.peptides.2010.04.030","article-title":"The structure of helokinestatin-5 and its biosynthetic precursor from Gila monster (Heloderma suspectum) venom: Evidence for helokinestatin antagonism of bradykinin-induced relaxation of rat tail artery smooth muscle","volume":"31","author":"Zhang","year":"2010","journal-title":"Peptides"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1111\/j.1096-0031.2001.tb00118.x","article-title":"Mitochondrial DNA evidence and evolution in Varanoidea (Squamata)","volume":"17","author":"Ast","year":"2001","journal-title":"Cladistics"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1071\/ZO08030","article-title":"Is body shape of varanid lizards linked with retreat choice?","volume":"56","author":"Thompson","year":"2008","journal-title":"Aust. J. Zool."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1098\/rsbl.2012.0460","article-title":"Molecular evidence for an Asian origin of monitor lizards followed by Tertiary dispersals to Africa and Australasia","volume":"8","author":"Vidal","year":"2012","journal-title":"Biol. Lett."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S0014-5793(99)01459-3","article-title":"MIT1, a black mamba toxin with a new and highly potent activity on intestinal contraction","volume":"461","author":"Schweitz","year":"1999","journal-title":"FEBS Lett."},{"key":"ref_69","unstructured":"Fry, B.G. (2015). B-type natriuretic peptides. Venomous Reptiles and Their Toxins: Evolution, Pathophysiology and Biodiscovery, Oxford University Press."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/0041-0101(90)90065-F","article-title":"Isolation and characterization of helothermine, a novel toxin from Heloderma horridum horridum (Mexican beaded lizard) venom","volume":"28","author":"Martin","year":"1990","journal-title":"Toxicon"},{"key":"ref_71","first-page":"A415","article-title":"Isolation and characterization of ryanodine receptor toxins from Heloderma horridum (mexican beaded lizard) venom","volume":"66","author":"Morrissette","year":"1994","journal-title":"Biophys. J."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2280","DOI":"10.1016\/S0006-3495(95)80410-8","article-title":"Primary structure and properties of helothermine, a peptide toxin that blocks ryanodine receptors","volume":"68","author":"Morrissette","year":"1995","journal-title":"Biophys. J."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/BF00232674","article-title":"The toxin helothermine affects potassium currents in newborn rat cerebellar granule cells","volume":"139","author":"Nobile","year":"1994","journal-title":"J. Membr. Biol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/BF00241369","article-title":"Helothermine, a lizard venom toxin, inhibits calcium current in cerebellar granules","volume":"110","author":"Nobile","year":"1996","journal-title":"Exp. Brain Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1111\/j.1476-5381.1990.tb12962.x","article-title":"Vascular effects of helodermin, helospectin I and helospectin II: A comparison with vasoactive intestinal peptide (VIP)","volume":"99","author":"Grundemar","year":"1990","journal-title":"Br. J. Pharmacol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.peptides.2003.11.010","article-title":"Helospectin I and II evoke vasodilation in the intact peripheral microcirculation","volume":"25","author":"Tsueshita","year":"2004","journal-title":"Peptides"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1097\/00004647-199901000-00007","article-title":"Helospectin-like peptides: Immunochemical localization and effects on isolated cerebral arteries and on local cerebral blood flow in the cat","volume":"19","author":"Uddman","year":"1999","journal-title":"J. Cereb. Blood Flow Metabol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/0006-291X(88)90183-0","article-title":"Purification and characterization of a lethal toxin from the venom of Heloderma horridum horridum","volume":"154","author":"Komori","year":"1988","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1111\/j.1399-3011.1997.tb01207.x","article-title":"Structure and other chemical characterizations of gila toxin, a lethal toxin from lizard venom","volume":"50","author":"Datta","year":"1997","journal-title":"J. Pept. Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1515\/bchm2.1969.350.2.821","article-title":"Isolation and properties of kallikrein from venom of gila monster (Heloderma suspectum)","volume":"350","author":"Mebs","year":"1969","journal-title":"Hoppe-Seylers Z. Physiol. Chem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/0020-711X(92)90033-W","article-title":"Isolation and characterization of arginine ester hydrolase from Heloderma horridum (beaded lizard) venom","volume":"24","author":"Nikai","year":"1992","journal-title":"Int. J. Biochem."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1016\/0020-711X(88)90226-1","article-title":"Kallikrein-like enzyme from the venom of Agkistrodon p. piscivorus","volume":"20","author":"Nikai","year":"1988","journal-title":"Int. J. Biochem."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/0003-9861(88)90594-2","article-title":"Isolation and characterization of horridum toxin with arginine ester hydrolase activity from Heloderma horridum (beaded lizard) venom","volume":"264","author":"Nikai","year":"1988","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"21975","DOI":"10.1016\/S0021-9258(20)80636-X","article-title":"Complete primary structure and biochemical properties of gilatoxin, a serine protease with kallikrein-like and angiotensin-degrading activities","volume":"268","author":"Utaisincharoen","year":"1993","journal-title":"J. Biol. Chem."},{"key":"ref_85","unstructured":"Fry, B.G. (2015). Kallikrein Enzymes In Venomous Reptiles and Their Toxins: Evolution, Pathophysiology and Biodiscovery, Oxford University Press."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/0005-2760(94)90139-2","article-title":"Effect on human platelet-aggregation of phospholipase a(2) purified from Heloderma horridum (beaded lizard) venom","volume":"1211","author":"Huang","year":"1994","journal-title":"Biochim. Biophys. Acta Lipids Lipid Metab."},{"key":"ref_87","unstructured":"Salemi, M., and Vandamme, A.-M. (2003). The Phylogenetic Handbook: A Practical Approach to DNA and Protein Phylogeny, Cambridge University Press."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1016\/j.cub.2009.09.022","article-title":"Convergent evolution of novel protein function in shrew and lizard venom","volume":"19","author":"Aminetzach","year":"2009","journal-title":"Curr. Biol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"35834","DOI":"10.1074\/jbc.M111.262303","article-title":"Structures of Phytophthora RXLR Effector Proteins a conserved but adaptable fold underpins functional diversity","volume":"286","author":"Boutemy","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"R152","DOI":"10.1016\/j.cub.2009.12.029","article-title":"Convergent Evolution: Pick Your Poison Carefully","volume":"20","author":"Brodie","year":"2010","journal-title":"Curr. Biol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1038\/hdy.2011.119","article-title":"Parallel signatures of sequence evolution among hearing genes in echolocating mammals: An emerging model of genetic convergence","volume":"108","author":"Davies","year":"2012","journal-title":"Heredity"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.crpv.2013.05.004","article-title":"Evolution of venom across extant and extinct eulipotyphlans","volume":"12","author":"Folinsbee","year":"2013","journal-title":"C. R. Palevol"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1093\/molbev\/mst011","article-title":"Molecular evolution of alpha-latrotoxin, the exceptionally potent vertebrate neurotoxin in black widow spider venom","volume":"30","author":"Garb","year":"2013","journal-title":"Mol. Biol. Evol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.ydbio.2012.09.014","article-title":"Convergent evolution of a reproductive trait through distinct developmental mechanisms in Drosophila","volume":"372","author":"Green","year":"2012","journal-title":"Dev. Biol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1074\/jbc.M115.691097","article-title":"A Single Glycan at the 99-Loop of Human Kallikrein-related Peptidase 2 Regulates Activation and Enzymatic Activity","volume":"291","author":"Guo","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/laban.426","article-title":"Exploring the molecular underpinnings of convergent evolution","volume":"42","author":"Harrington","year":"2013","journal-title":"Lab. Anim."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1146\/annurev-genom-082509-141646","article-title":"Genome Evolution in Reptilia, the Sister Group of Mammals","volume":"Volume 11","author":"Chakravarti","year":"2010","journal-title":"Annual Review of Genomics and Human Genetics"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1210\/er.2009-0034","article-title":"Kallikreins on Steroids: Structure, Function, and Hormonal Regulation of Prostate-Specific Antigen and the Extended Kallikrein Locus","volume":"31","author":"Lawrence","year":"2010","journal-title":"Endocr. Rev."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1016\/j.toxicon.2012.02.012","article-title":"Venomous mammals: A review","volume":"59","author":"Verli","year":"2012","journal-title":"Toxicon"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1111\/j.1558-5646.2011.01289.x","article-title":"Convergence, adaptation, and constraint","volume":"65","author":"Losos","year":"2011","journal-title":"Evolution"},{"key":"ref_101","first-page":"1235","article-title":"The loci of repeated evolution: A catalog of genetic hotspots of phenotypic variation","volume":"67","author":"Martin","year":"2013","journal-title":"Evolution"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1002\/ajpa.22280","article-title":"The convergent evolution of blue iris pigmentation in primates took distinct molecular paths","volume":"151","author":"Meyer","year":"2013","journal-title":"Am. J. Phys. Anthropol."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Pavlopoulou, A., Pampalakis, G., Michalopoulos, I., and Sotiropoulou, G. (2010). Evolutionary History of Tissue Kallikreins. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0013781"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.cub.2009.11.015","article-title":"Identical Skin Toxins by Convergent Molecular Adaptation in Frogs","volume":"20","author":"Roelants","year":"2010","journal-title":"Curr. Biol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1111\/j.1600-0722.2011.00834.x","article-title":"Expression of kallikrein-related peptidase 4 in dental and non-dental tissues","volume":"119","author":"Simmer","year":"2011","journal-title":"Eur. J. Oral Sci."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1002\/prot.24066","article-title":"Protein-protein interaction network-based detection of functionally similar proteins within species","volume":"80","author":"Song","year":"2012","journal-title":"Proteins-Struct. Funct. Bioinform."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1093\/molbev\/mst199","article-title":"The first venomous crustacean revealed by transcriptomics and functional morphology: Remipede venom glands express a unique toxin cocktail dominated by enzymes and a neurotoxin","volume":"31","author":"Blanke","year":"2014","journal-title":"Mol. Biol. Evol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1093\/molbev\/msr180","article-title":"A limited role for gene duplications in the evolution of platypus venom","volume":"29","author":"Wong","year":"2012","journal-title":"Mol. Biol. Evol."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Yennamalli, R.M., Rader, A.J., Wolt, J.D., and Sen, T.Z. (2011). Thermostability in endoglucanases is fold-specific. BMC Struct. Biol., 11.","DOI":"10.1186\/1472-6807-11-10"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1093\/molbev\/msw065","article-title":"Target-driven positive selection at hot spots of scorpion toxins uncovers their potential in design of insecticides","volume":"33","author":"Zhu","year":"2016","journal-title":"Mol. Biol. Evol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1016\/j.bcp.2010.07.008","article-title":"Drosotoxin, a selective inhibitor of tetrodotoxin-resistant sodium channels","volume":"80","author":"Zhu","year":"2010","journal-title":"Biochem. Pharmacol."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Zhu, S.Y., Peigneur, S., Gao, B., Lu, X.X., Cao, C.Y., and Tytgat, J. (2012). Evolutionary diversification of mesobuthus alpha-scorpion toxins affecting sodium channels. Mol. Cell. Proteom., 11.","DOI":"10.2210\/pdb2lkb\/pdb"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/S0041-0101(09)80007-X","article-title":"Purification and pharmacological characterization of peptide toxins from the black mamba (Dendroaspis polylepis) venom","volume":"28","author":"Schweitz","year":"1990","journal-title":"Toxicon"},{"key":"ref_114","first-page":"1","article-title":"Die familie der warane (Varanidae)","volume":"465","author":"Mertens","year":"1942","journal-title":"Abh. Senckenberg. Naturforschenden Ges."},{"key":"ref_115","first-page":"797","article-title":"A functional interpretation of the varanid dentition (Reptilia, Lacertilia, Varanidae)","volume":"125","author":"Rieppel","year":"1979","journal-title":"Gegenbaurs Morphol. Jahrb."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1017\/S0094837300013956","article-title":"The serrated teeth of tyrannosaurid dinosaurs, and biting structures in other animals","volume":"18","author":"Abler","year":"1992","journal-title":"Paleobiology"},{"key":"ref_117","first-page":"158","article-title":"Mandibular mechanics in Varanus niloticus (Reptilia: Lacertilia)","volume":"35","author":"Rieppel","year":"1979","journal-title":"Herpetologica"},{"key":"ref_118","unstructured":"Horn, H.G., Boehme, W., and Krebs, U. (2007). Comparative spatial ecology of two small arboreal monitors in northern Australia. Advances in Monitor Research III, Mertensiella 16."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"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 Genet., 11.","DOI":"10.1371\/journal.pgen.1005596"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1071\/ZO11082","article-title":"Diet analysis of mammals, raptors and reptiles in a complex predator assemblage in the Blue Mountains, eastern Australia","volume":"59","author":"Pascoe","year":"2012","journal-title":"Aust. J. Zool."},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Pianka, E.R., King, D., and King, R.A. (2004). Varanoid Lizards of the World, Indiana University Press.","DOI":"10.2307\/j.ctt2005wjp"},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Bull, J.J., Jessop, T.S., and Whiteley, M. (2010). Deathly drool: Evolutionary and ecological basis of septic bacteria in Komodo dragon mouths. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0011097"},{"key":"ref_123","first-page":"46","article-title":"Ecological function of venom in Varanus, with a compilation of dietary records from the literature","volume":"3","author":"Arbuckle","year":"2009","journal-title":"Biawak"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1098\/rstb.1998.0267","article-title":"Field biology of the platypus (Ornithorhynchus anatinus): Historical and current perspectives","volume":"353","author":"Grant","year":"1998","journal-title":"Philos. Trans. R. Soc. B Biol. Sci."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Malhotra, A., and Gopalakrishnakone, P. (2015). Evolutionary context of venom in animals. Evolution of Venomous Animals and Their Toxins, Springer.","DOI":"10.1007\/978-94-007-6727-0"},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Harris, R.J., and Arbuckle, K. (2016). Tempo and mode of the evolution of venom and poison in tetrapods. Toxins, 8.","DOI":"10.3390\/toxins8070193"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1016\/j.toxicon.2005.02.016","article-title":"Practical applications of snake venom toxins in haemostasis","volume":"45","author":"Marsh","year":"2005","journal-title":"Toxicon"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/j.jprot.2013.07.020","article-title":"Proteomic comparison of Hypnale hypnale (Hump-Nosed Pit-Viper) and Calloselasma rhodostoma (Malayan Pit-Viper) venoms","volume":"91C","author":"Ali","year":"2013","journal-title":"J. Proteom."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.jprot.2014.09.003","article-title":"Extreme venom variation in Middle Eastern vipers: A proteomics comparison of Eristicophis macmahonii, Pseudocerastes fieldi and Pseudocerastes persicus","volume":"116","author":"Ali","year":"2015","journal-title":"J. Proteom."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.jprot.2013.05.034","article-title":"Dracula\u2019s children: Molecular evolution of vampire bat venom","volume":"89","author":"Low","year":"2013","journal-title":"J. Proteom."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1016\/j.toxicon.2009.10.010","article-title":"Biological and proteomic analysis of venom from the Puerto Rican Racer (Alsophis portoricensis: Dipsadidae)","volume":"55","author":"Weldon","year":"2010","journal-title":"Toxicon"},{"key":"ref_132","unstructured":"R-Core-Team (2017, June 04). R: A Language and Environment for Statistical Computing. Available online: https:\/\/www.R-project.org\/."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1093\/bioinformatics\/btg412","article-title":"APE: Analyses of phylogenetics and evolution in R language","volume":"20","author":"Paradis","year":"2004","journal-title":"Bioinformatics"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1111\/j.2041-210X.2011.00169.x","article-title":"phytools: An R package for phylogenetic comparative biology (and other things)","volume":"3","author":"Revell","year":"2012","journal-title":"Methods Ecol. Evol."},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Garamszegi, L.Z. (2014). A Primer on Phylogenetic Generalised Least Squares. Modern Phylogenetic Comparative Methods and Their Application in Evolutionary Biology, Springer-Verlag.","DOI":"10.1007\/978-3-662-43550-2"},{"key":"ref_136","unstructured":"Orme, D., Freckleton, R., Thomas, G., Petzoldt, T., Fritz, S., Isaac, N., and Pearse, W. (2017, August 06). The Caper Package: Comparative Analyses of Phylogenetics and Evolution in R, Version 0.5.2. Available online: https:\/\/cran.r-project.org\/web\/packages\/caper\/vignettes\/caper.pdf."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S0022-2836(05)80360-2","article-title":"Basic local alignment search tool","volume":"215","author":"Altschul","year":"1990","journal-title":"J. Mol. Biol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"D36","DOI":"10.1093\/nar\/gks1195","article-title":"GenBank","volume":"41","author":"Benson","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"D32","DOI":"10.1093\/nar\/gkt1030","article-title":"GenBank","volume":"42","author":"Benson","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Edgar, R.C. (2004). MUSCLE: A multiple sequence alignment method with reduced time and space complexity. BMC Bioinform., 5.","DOI":"10.1186\/1471-2105-5-113"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"3276","DOI":"10.1093\/bioinformatics\/btu531","article-title":"AliView: A fast and lightweight alignment viewer and editor for large datasets","volume":"30","author":"Larsson","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1093\/sysbio\/sys029","article-title":"MrBayes 3.2: Efficient Bayesian phylogenetic inference and model choice across a large model space","volume":"61","author":"Ronquist","year":"2012","journal-title":"Syst. Biol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1038\/nprot.2015.053","article-title":"The Phyre2 web portal for protein modeling, prediction and analysis","volume":"10","author":"Kelley","year":"2015","journal-title":"Nat. Protoc."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera\u2014A visualization system for exploratory research and analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J. Comput. Chem."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1093\/bioinformatics\/17.8.700","article-title":"AL2CO: Calculation of positional conservation in a protein sequence alignment","volume":"17","author":"Pei","year":"2001","journal-title":"Bioinformatics"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1093\/molbev\/mst030","article-title":"FUBAR: A fast, unconstrained bayesian approximation for inferring selection","volume":"30","author":"Murrell","year":"2013","journal-title":"Mol. Biol. Evol."},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Murrell, B., Wertheim, J.O., Moola, S., Weighill, T., Scheffler, K., and Kosakovsky Pond, S.L. (2012). Detecting individual sites subject to episodic diversifying selection. PLoS Genet., 8.","DOI":"10.1371\/journal.pgen.1002764"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1093\/bioinformatics\/bti079","article-title":"HyPhy: Hypothesis testing using phylogenies","volume":"21","author":"Pond","year":"2005","journal-title":"Bioinformatics"}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/9\/8\/242\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:41:34Z","timestamp":1760208094000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/9\/8\/242"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8,6]]},"references-count":148,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2017,8]]}},"alternative-id":["toxins9080242"],"URL":"https:\/\/doi.org\/10.3390\/toxins9080242","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,8,6]]}}}