Widespread convergence in toxin resistance by predictable molecular evolution Ujvari, Beata, Casewell, Nicholas R., Sunagar, Kartik, Arbuckle, Kevin, Wüster, Wolfgang, Lo, Nathan, O'Meally, Denis, Beckmann, Christa, King, Glenn F., Deplazes, Evelyne and Madsen, Thomas 2015, Widespread convergence in toxin resistance by predictable molecular evolution, Proceedings of the National Academy of Sciences, vol. 112, no. 38, pp. 11911-11916, doi: 10.1073/pnas.1511706112. Attached Files Name Description MIMEType Size Downloads Title Widespread convergence in toxin resistance by predictable molecular evolution Author(s) Ujvari, Beata orcid.org/0000-0003-2391-2988 Casewell, Nicholas R. Sunagar, Kartik Arbuckle, Kevin Wüster, Wolfgang Lo, Nathan O'Meally, Denis Beckmann, Christa orcid.org/0000-0002-7904-7228 King, Glenn F. Deplazes, Evelyne Madsen, Thomas Journal name Proceedings of the National Academy of Sciences Volume number 112 Issue number 38 Start page 11911 End page 11916 Total pages 6 Publisher National Academy of Sciences Place of publication Washington, D.C. Publication date 2015-09-22 ISSN 1091-6490 Keyword(s) bufotoxin cardenolide constraint genotype phenotype ion transporters parallelism bufanolides Cardiac Glycosides isoelectric point molecular sequence data phylogeny Summary The question about whether evolution is unpredictable and stochastic or intermittently constrained along predictable pathways is the subject of a fundamental debate in biology, in which understanding convergent evolution plays a central role. At the molecular level, documented examples of convergence are rare and limited to occurring within specific taxonomic groups. Here we provide evidence of constrained convergent molecular evolution across the metazoan tree of life. We show that resistance to toxic cardiac glycosides produced by plants and bufonid toads is mediated by similar molecular changes to the sodium-potassium-pump (Na(+)/K(+)-ATPase) in insects, amphibians, reptiles, and mammals. In toad-feeding reptiles, resistance is conferred by two point mutations that have evolved convergently on four occasions, whereas evidence of a molecular reversal back to the susceptible state in varanid lizards migrating to toad-free areas suggests that toxin resistance is maladaptive in the absence of selection. Importantly, resistance in all taxa is mediated by replacements of 2 of the 12 amino acids comprising the Na(+)/K(+)-ATPase H1-H2 extracellular domain that constitutes a core part of the cardiac glycoside binding site. We provide mechanistic insight into the basis of resistance by showing that these alterations perturb the interaction between the cardiac glycoside bufalin and the Na(+)/K(+)-ATPase. Thus, similar selection pressures have resulted in convergent evolution of the same molecular solution across the breadth of the animal kingdom, demonstrating how a scarcity of possible solutions to a selective challenge can lead to highly predictable evolutionary responses. Language eng DOI 10.1073/pnas.1511706112 Field of Research 060305 Evolution of Developmental Systems Socio Economic Objective 970106 Expanding Knowledge in the Biological Sciences HERDC Research category C1 Refereed article in a scholarly journal ERA Research output type C Journal article Copyright notice ©2015, National Academy of Sciences Persistent URL http://hdl.handle.net/10536/DRO/DU:30079401 Document type: Journal Article Collections: School of Life and Environmental Sciences Centre for Integrative Ecology Related Links Link Description Connect to published version Go to link with your DU access privileges     Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved. Versions Version Filter Type Mon, 09 Nov 2015, 15:58:57 EST Mon, 18 Jul 2016, 17:34:50 EST Tue, 19 Jul 2016, 05:00:32 EST Tue, 19 Jul 2016, 06:12:07 EST Tue, 19 Jul 2016, 11:08:49 EST Tue, 19 Jul 2016, 11:09:55 EST Wed, 12 Oct 2016, 14:15:57 EST Mon, 30 Jan 2017, 09:39:33 EST Tue, 31 Jan 2017, 08:28:05 EST Filtered Full Citation counts:   Cited 39 times in TR Web of Science Cited 42 times in Scopus Search Google Scholar Access Statistics: 198 Abstract Views, 3 File Downloads  -  Detailed Statistics Created: Mon, 18 Jul 2016, 17:34:50 EST

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