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.

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Title Widespread convergence in toxin resistance by predictable molecular evolution
Author(s) Ujvari, BeataORCID iD for Ujvari, Beata orcid.org/0000-0003-2391-2988
Casewell, Nicholas R.
Sunagar, Kartik
Arbuckle, Kevin
Wüster, Wolfgang
Lo, Nathan
O'Meally, Denis
Beckmann, ChristaORCID iD for 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

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