Modeling defensive functions of alkaloids within diverse chemical portfolios

Studies of the evolution of anti-predatory phenotypes such as aposematic signals have proven informative to demonstrate the role of selection on phenotypic divergence. Oophaga pumilio show high variance in both elements of their aposematic signals; visual cues consisting of color patterns, as well as their alkaloid chemical defenses where an individual frog can possess dozens of alkaloid types. Disentangling the function of individual alkaloids is therefore complicated due to various modes of chemical defenses, making simple comparisons between levels of relative ‘toxicity’ between populations difficult until we can elucidate the defensive capabilities of alkaloids. In this study we model binding affinity of the most abundant alkaloids found in divergent populations of O. pumilio which we discovered had a high affinity for binding with Muscarinic acetylcholine receptors in various potential predator classes. Molecular interaction and docking experiments indicate that interactions between alkaloid and muscarinic receptors are highly conserved, and muscarinic receptors themselves show evidence of strong purifying selection. Therefore, we predict functional redundancy is plausible among the most common alkaloids against common targets, and these alkaloids likely function similarly across diverse suites of predators. This affords a predictable baseline of defenses for this combination of alkaloids and receptors between divergent populations which vary in aposematic signals.