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Widespread convergence in toxin resistance by predictable molecular evolution

Ujvari, Beata, Casewell, Nicholas ORCID: https://orcid.org/0000-0002-8035-4719, 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 of the United States of America, Vol 112, Issue 38, pp. 11911-11916.

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Abstract

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.

Item Type: Article
Subjects: QU Biochemistry > Genetics > QU 500 Genetic phenomena
QV Pharmacology > Cardiovascular Agents. Renal Agents > QV 150 Cardiovascular agents
QW Microbiology and Immunology > Immune Responses > QW 700 Infection. Mechanisms of infection and resistance.
Faculty: Department: Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI): https://doi.org/10.1073/pnas.1511706112
Depositing User: Jessica Jones
Date Deposited: 16 Feb 2016 11:09
Last Modified: 06 Feb 2018 13:11
URI: http://archive.lstmed.ac.uk/id/eprint/5646

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