Cardenolides, toxicity, and the costs of sequestration in the coevolutionary interaction between monarchs and milkweeds

Significance Interactions between plants and herbivores constitute a major pathway of energy transfer up the food chain. As a consequence, evolution by natural selection has honed the chemically mediated antagonistic interactions between these groups. Monarch butterflies and milkweeds serve as royal representatives in deciphering such coevolution, and our study takes a mechanistic and manipulative approach to understand how the tropical milkweed, Asclepias curassavica , defends itself against monarch butterflies, which would seem to be impervious feeders. By directly observing plant–herbivore interactions and coupling this with experiments on isolated toxins and the monarch’s neural sodium-potassium pump enzymes, we show that tropical milkweed produces a burdensome cardenolide toxin, and monarchs convert it to less toxic compounds, the latter sequestered for their own benefit.