Why poisonous frogs don’t croak

As every school kid will tell you, South America boasts some fearsomely poisonous little frogs.

These amphibians, such as the little devil poison frog (Dendrobates sylvaticus), have sometimes been used by indigenous hunter-gather communities as an aid to food capture, with arrows being coated in the highly toxic exudations.

A pertinent question that arises when considering these small, brightly coloured frogs – as smarter school kids quickly realise – is why they don’t themselves fall victim to their own defence mechanism. 

Now, research by Rebecca Tarvin from the University of Texas, US, and published in the journal Science, has uncovered the genetic basis of this immunity.

The frog species all produce a powerful neurotoxin called epibatidine, which acts by binding to proteins called acetylcholine receptors located on the cell membranes of whichever animal is attempting to eat them. Acetylcholine is a key neurotransmitter.

Clearly, the frogs themselves do not fall prey to their own poison, but why the self-produced epibatidine did not cripple their own neurotransmission pathways was unclear.

To find out, the team expressed frog acetylcholine receptors in a human cell line, and then analysed the DNA.

The results told a story of adaptive evolution. The researchers found that a single changed amino acid altered the receptor function sufficiently to nullify the normally lethal effects of epibatidine. However, in doing so it also significantly reduced the frog’s sensitivity to acetylcholine, dampening its nervous system.

This must have placed a considerable burden on the little amphibians, the researchers suggest, trading off poisonous protection from predators against reduced functionality.

The situation was later rectified, however, by the emergence of three new amino acids that work to reboot the animals’ acetylcholine sensitivity (and thus restore normal neurotransmission) while maintaining the immunity to epibatidine.

Tarvin and her colleagues conclude that protein evolution can sometimes be part of a complex balance of survival challenges, and that some adaptations – such as the little devil’s poison – initially come at substantial cost.