Beata Ujvari, Nicholas R. Casewell, Kartik Sunagar, Kevin Arbuckle, Wolfgang Wüster, Nathan Lo, Denis O’Meally, Christa Beckmann, Glenn F. King, Evelyne Deplazes, and Thomas Madsen

ECOLOGY

Significance

Convergence has strong bearing on the fundamental debate about whether evolution is stochastic and unpredictable or subject to constraints. Here we show that, in certain circumstances, evolution can be highly predictable. We demonstrate that several lineages of insects, amphibians, reptiles, and mammals have utilized the same molecular solution, via the process of convergence, to evolve resistance to toxic cardiac glycosides produced defensively by plants and bufonid toads. The repeatability of this process across the animal kingdom demonstrates that evolution can be constrained to proceed along highly predictable pathways at molecular and functional levels. Our study has important implications for conservation biology by providing a predictive framework for assessing the vulnerability of native fauna to the introduction of invasive toxic toads.

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.

See: http://www.pnas.org/content/112/38/11911.abstract

PNAS September 2015, vol. 112 no. 38: 11911–11916

Fig. 1.

Convergent molecular evolution of resistance to toad toxins in squamate reptiles and reversal to susceptibility in Australian varanid lizards. The timing of changes to resistant amino acids in the H1–H2 extracellular domain of the Na⁺/K⁺-ATPase gene correlates with taxa that feed on toads. Pictures of toads indicate clades of taxa that are known to feed on toads without ill effects. The picture of a toad circled in red highlights that Australian varanid lizards have reverted back to being susceptible to toad toxins. Colored branches indicate the amino acid composition at key positions (susceptible, Q111 and G120; resistant, L111 and R120), and changes in color represent the reconstructed timings of amino acid replacements. Sites 111 and 120 were found to be coevolving (pp = 0.83). The character state (resistant or susceptible) at all key nodes in the tree, including those relevant for timings of character change, are strongly supported (pp ≥ 0.95); nodes with asterisks represent those falling beneath this threshold. Species tree was generated from refs. 57, 58.