Researchers show that the mechanism behind poisonous frogs gaining resistance to their own toxins is not
only complicated, but it’s also costly.
In a publication recently released in Science, scientists not only wanted to identify the genetic changes that lead frogs to become resistant to their own toxins, but to understand the mechanism frogs are using to compensate for these genetic changes. Interestingly, scientists at the University of Texas at Austin identified a genetic change that provides one group of frogs their immunity to a particularly lethal toxin, but it also disrupts a key chemical messenger pathway in the brain. Some dart frogs have a deadly cocktail of alkaloid molecules located on their skin as a defense mechanism again predators. These deadly toxins are picked up through a frog’s diet and can vary greatly through different species. Previous studies have shown that frogs become resistant to their own toxins by identifying the proteins these toxin molecules bind to. One species of frogs develop a toxin called epibatidine, which binds to proteins that target acetylcholine, which is a chemical messenger important for brain function. Scientists wanted to identify the differences between the acetylcholine receptor in poisonous frog species as compared to non-poisonous frog species. In order to test this, researchers inserted human acetylcholine receptor proteins (not resistant to epibatidine) into frog eggs and altered select amino acids in the human code that differs from the amino acid code of poisonous frogs in order to make them resistant to epibatidine. Shockingly, scientists observed that this process was not as straightforward as previously expected. When researchers altered these amino acids, it made the human protein resistant to epibatidine but it altered its reaction to acetylcholine, making it more difficult to bind to the receptor and thus possibly impairing its mechanism. However, the frogs do not have an impaired function, because these frogs contain other amino acid replacements on the acetylcholine receptors to compensate. Interestingly, these resistant amino acid changes seem to have evolved several times in poisonous frogs, but they all don’t have the same amino acid changes, but still recover the function.
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