The Evolutionary Ecology of Cardiotonic Steroids
Cardiotonic steroids are potent plant-derived toxins used by many insects as chemical defences against predators. These compounds, which target the Na⁺/K⁺-ATPase enzyme, are sequestered from host plants and often advertised through conspicuous warning signals—a strategy known as aposematism.
Our research investigates the evolutionary and ecological dynamics of cardiotonic steroid use in chemically defended insects, such as the large milkweed bug (Oncopeltus fasciatus). We explore how variation in toxin quantity and composition shapes—and is shaped by—biotic interactions, and how these pressures maintain diversity in warning signals.
Oncopeltus fasciatus on Asclepias tuberosa. Image Martin LaBar
“The ‘tenacity of life’ so characteristic of the warningly coloured lepidoptera on which [predators] feed, is to some extent also apparent in the vertebrate predators that attack them and appears to indicate a rather widespread phenomenon which is by no means understood.”
— Miriam Rothschild, 1972
At the molecular level, we focus on the Na⁺/K⁺-ATPase gene family, the primary target of cardiotonic steroids. By analysing the evolution of resistance-conferring mutations and functionally characterising their effects, we uncover how insects and vertebrates adapt to the toxins they consume—and how these adaptations influence ecological outcomes.
Publications
S. Mohammadi, S. Pradhan, F.G. Hoffmann, S. Herrera-Álvarez, Y. Deng, A. Eacock, S. Dobler, J. F. Storz, H.M. Rowland (2025) Historical Contingency Shapes Toxin Resistance in a Specialist Avian Predator. bioRxiv 2025.07.04.662692; doi: https://doi.org/10.1101/2025.07.04.662692
Rubiano-Buitrago, R., Pradhan, S., Aceves-Aparicio, A., Mohammadi, S., Paetz, C., Rowland, H. M. (2024) Cardenolides in the defensive fluid of adult large milkweed bugs have differential potency on vertebrate and invertebrate predator Na+/K+–ATPases. Authorea https://doi.org/10.22541/au.169658664.45852491/v1
Rubiano-Buitrago, P., Pradhan, S., Grabe, V., Aceves-Aparicio, A., Paetz, C., & Rowland, H. M. (2023). Differential accumulation of cardenolides from Asclepias curassavica by large milkweed bugs does not correspond to availability in seeds or biological activity on the bug Na+/K+-ATPase. Frontiers in Ecology and Evolution, 11, 1175205.
Heyworth, H. C., Pokharel, P., Blount, J.D., Mitchell, C., Petschenka, G., Rowland, H.M. (2023) Antioxidant availability trades off with warning signals and toxin sequestration in the large milkweed bug (Oncopeltus fasciatus). Ecology and Evolution, 13, e09971. https://doi.org/10.1002/ece3.9971
Mohammadi, S., Özdemir, H. I., Ozbek, P., Sumbul, F., Stiller, J., Deng, J., Crawford, A. J., Rowland, H. M., Storz, J. F., Andolfatto, P., Dobler, S. (2022) Epistatic effects between amino acid insertions and substitutions mediate toxin-resistance of vertebrate Na+,K+-ATPases. Molecular Biology and Evolution, 39, msac258, https://doi.org/10.1093/molbev/msac258