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Grant","award":["11C6521N"],"award-info":[{"award-number":["11C6521N"]}]},{"name":"Rufford Foundation Small Grant","award":["15255-1"],"award-info":[{"award-number":["15255-1"]}]},{"name":"Rufford Foundation Small Grant","award":["RIF4"],"award-info":[{"award-number":["RIF4"]}]},{"name":"University of Wolverhampton","award":["DP210102406"],"award-info":[{"award-number":["DP210102406"]}]},{"name":"University of Wolverhampton","award":["G0D3214N"],"award-info":[{"award-number":["G0D3214N"]}]},{"name":"University of Wolverhampton","award":["SRP-30"],"award-info":[{"award-number":["SRP-30"]}]},{"name":"University of Wolverhampton","award":["11C6521N"],"award-info":[{"award-number":["11C6521N"]}]},{"name":"University of Wolverhampton","award":["15255-1"],"award-info":[{"award-number":["15255-1"]}]},{"name":"University of Wolverhampton","award":["RIF4"],"award-info":[{"award-number":["RIF4"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Predatory innovations impose reciprocal selection pressures upon prey. The evolution of snake venom alpha-neurotoxins has triggered the corresponding evolution of resistance in the post-synaptic nicotinic acetylcholine receptors of prey in a complex chemical arms race. All other things being equal, animals like caecilians (an Order of legless amphibians) are quite vulnerable to predation by fossorial elapid snakes and their powerful alpha-neurotoxic venoms; thus, they are under strong selective pressure. Here, we sequenced the nicotinic acetylcholine receptor alpha-1 subunit of 37 caecilian species, representing all currently known families of caecilians from across the Americas, Africa, and Asia, including species endemic to the Seychelles. Three types of resistance were identified: (1) steric hindrance from N-glycosylated asparagines; (2) secondary structural changes due to the replacement of proline by another amino acid; and (3) electrostatic charge repulsion of the positively charged neurotoxins, through the introduction of a positively charged amino acid into the toxin-binding site. We demonstrated that resistance to alpha-neurotoxins convergently evolved at least fifteen times across the caecilian tree (three times in Africa, seven times in the Americas, and five times in Asia). Additionally, as several species were shown to possess multiple resistance modifications acting synergistically, caecilians must have undergone at least 20 separate events involving the origin of toxin resistance. On the other hand, resistance in non-caecilian amphibians was found to be limited to five origins. Together, the mutations underlying resistance in caecilians constitute a robust signature of positive selection which strongly correlates with elapid presence through both space (sympatry with caecilian-eating elapids) and time (Cenozoic radiation of elapids). Our study demonstrates the extent of convergent evolution that can be expected when a single widespread predatory adaptation triggers parallel evolutionary arms races at a global scale.<\/jats:p>","DOI":"10.3390\/ijms241411353","type":"journal-article","created":{"date-parts":[[2023,7,13]],"date-time":"2023-07-13T01:43:22Z","timestamp":1689212602000},"page":"11353","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Resistance Is Not Futile: Widespread Convergent Evolution of Resistance to Alpha-Neurotoxic Snake Venoms in Caecilians (Amphibia: Gymnophiona)"],"prefix":"10.3390","volume":"24","author":[{"given":"Marco","family":"Mancuso","sequence":"first","affiliation":[{"name":"Amphibian Evolution Lab, Biology Department, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5399-0130","authenticated-orcid":false,"given":"Shabnam","family":"Zaman","sequence":"additional","affiliation":[{"name":"Amphibian Evolution Lab, Biology Department, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon T.","family":"Maddock","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, The Natural History Museum, London SW7 5BD, UK"},{"name":"School of Life Sciences, University of Wolverhampton, Wulfruna Street, Wolverhampton WV1 1LY, UK"},{"name":"Island Biodiversity and Conservation Centre, University of Seychelles, Mah\u00e9 P.O. Box 1348, Seychelles"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachunliu G.","family":"Kamei","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, The Natural History Museum, London SW7 5BD, UK"},{"name":"Amphibians and Reptiles Division, The Field Museum of Natural History, 1400 S Lake Shore Dr., Chicago, IL 60605, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Salazar-Valenzuela","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n de la Biodiversidad y Cambio Clim\u00e1tico (BioCamb) e Ingenier\u00eda en Biodiversidad y Recursos Gen\u00e9ticos, Facultad de Ciencias de Medio Ambiente, Universidad Indoam\u00e9rica, Machala y Sabanilla, Quito EC170301, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Wilkinson","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, The Natural History Museum, London SW7 5BD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Roelants","sequence":"additional","affiliation":[{"name":"Amphibian Evolution Lab, Biology Department, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium"}],"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 Evolutionary Lab, School of Biological Sciences, University of Queensland, St. Lucia, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0300-9629(95)98515-I","article-title":"Cutaneous granular glands and amphibian venoms","volume":"111","author":"Toledo","year":"1995","journal-title":"Comp. 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