Poison Frogs: Evolution of Epibatidine Resistance

Gene Yang ‘19


Figure 1: The poison frog, Ameerega bassleri, is one of the three studied lineages of frogs that evolved resistance to epibatidine, a toxin lethal in microgram-doses.

Animals that use toxins as anti-predator defense usually evolve a method of resistance, often at a high physiological cost, to prevent self-intoxication. Poisonous frogs, a broad polyphyletic group within the order Anura, often use one such method known as target site insensitivity, which is the alteration of the molecular target of the toxin to disallow the toxin from binding. Researchers from University of Texas and Harvard University studied epibatidine resistance in poison frogs and discovered the specific amino acid replacements in the toxin’s molecular target: nAChR. nAChR makes resistance possible—a result that provides insight into the evolution of toxin defense.

Epibatidine is a toxin that binds and activates the nicotinic acetylcholine receptor (nAChR), a common receptor protein that normally responds to the neurotransmitter acetylcholine (ACh). The study began by sequencing the genes of the three genera of poison frogs known to utilize epibatidine (Oophaga, Ameerega, and Epipedobates), and then comparing those genes to those of 19 other lineages of poison frogs. This resulted in the identification of unique amino acids found in the nAChR of epibatidine-wielding poison frogs that were not present in non-epibatidine lineages. Site-directed mutagenesis, which is the intentional change of a specific DNA sequence, was first used to express wild-type nAChR and epibatidine-resistant nAChR in Xenopus laevis oocytes. Both the wild-type nAChR groups and epibatidine-resistant nAChR groups were then exposed to ACh and epibatidine.

The results revealed that a single amino acid replacement in nAChR, from serine to cysteine (S108C), was responsible for decreased epibatidine sensitivity. However, this convergently evolved mutation also decreased acetylcholine sensitivity, and further amino acid replacements unique to each lineage were needed to restore nAChR functionality. The amino acid replacement S108C demonstrated that this convergent evolution mutation provides a strong selective advantage.


  1. R.D. Tarvin, et al., Interacting amino acid replacements allow poison frogs to evolve epibatidine resistance. Science 357, 1261-1266 (2017). doi: 10.1126/science.aan5061
  2. Image retrieved from: https://upload.wikimedia.org/wikipedia/commons/e/e8/Flickr_-_ggallice_-_Pleasing_poison_frog.jpg

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