Widespread convergence in toxin resistance by predictable molecular evolution

Ujvari, Beata, Casewell, Nicholas R., Sunagar, Kartik, Arbuckle, Kevin, Wuester, 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, 112 38: 11911-11916. doi:10.1073/pnas.1511706112

Author Ujvari, Beata
Casewell, Nicholas R.
Sunagar, Kartik
Arbuckle, Kevin
Wuester, Wolfgang
Lo, Nathan
O'Meally, Denis
Beckmann, Christa
King, Glenn F.
Deplazes, Evelyne
Madsen, Thomas
Title Widespread convergence in toxin resistance by predictable molecular evolution
Journal name Proceedings of the National Academy of Sciences of the United States of America   Check publisher's open access policy
ISSN 0027-8424
Publication date 2015-09-01
Sub-type Article (original research)
DOI 10.1073/pnas.1511706112
Open Access Status Not Open Access
Volume 112
Issue 38
Start page 11911
End page 11916
Total pages 6
Place of publication Washington, DC, United States
Publisher National Academy of Sciences
Language eng
Formatted 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.
Keyword Constraint
Genotype phenotype
Ion transporters
Bufotoxin cardenolide
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 22 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 25 times in Scopus Article | Citations
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