The rough-skinned newt (Taricha granulosa) is toxic – killing all that dare to eat it – except for the predatory common garter snake (Thamnophis sirtalis). The two creatures are locked in an arms race of evolution where prey evolves to be inedible so predator evolves resistance to prey’s toxicity, then prey evolves higher toxicity levels and so forth. A team at Virginia Tech have now identified when the resistance first appeared in the ancestors of garter snakes, and how exactly they fight the toxin.

The weapons

TTX is a neurotoxin produced by the rough-skinned newts and is found in other animals like some pufferfish species (Tetraodontidae) and the blue-ringed octopus (Hapalochlaena). It affects proteins called sodium channels in neurons, which blocks signals from moving through the brain or to the muscles. This can cause paralysis and seizures. TTX is extremely toxic, with newts containing more than enough of it to kill a human.

Garter snakes are the only confirmed animal to be able to eat these poisonous newts. They do this by having a different code in the genes for the sodium channels, giving the channels a different structure than other species. This allows the snakes to resist the paralysis caused by the toxin in both their nerves and their muscles.

The evolutionary arms race

The team sequenced the genes of three sodium channels found in 82 species. They used 78 species of snake, 2 lizard species, 1 bird and 1 turtle, allowing the changes in the sequence to be mapped over time as the animals evolved. As time went on, it was found that some groups of snakes kept building up their resistance to TTX and that they always evolved the resistant nerves first, followed by the resistant muscles. The researchers discovered that the toxicity-resistance was first gained by garter snake ancestors about 40 million years ago. An important milestone, as without this first step the snakes wouldn’t have ever been able to eat the newts and take part in this evolutionary contest.

But as the snakes gained stronger resistance to the toxic newts, this created pressure on the newts to increase the level of their toxicity to prevent the snakes from eating them. This is the arms race. As one side develops their weapons or defence, the other must also do so in order to survive.

Without this selective pressure, the snakes stop developing their resistance. This was discovered by surveying newts at 28 locations down the West coast. It was found that in 1/3 of the locations, less resistant snakes were still hunting the rough-skinned newts. Even at this lower level of resistance, they were still able to predate the newts, suggesting there is currently no pressure for the snakes to develop stronger resistance. This could mean that the snakes are starting to gain the advantage over the newts.

Snakes are pulling ahead

It appears that the garter snakes are starting to outstrip the newts by developing their resistance a lot faster than the newts can increase their toxicity. This is because of several factors. One is that increasing resistance to TTX only requires a few changes as only a small number of genes are involved in coding for the sodium channels. Changing toxicity, on the other hand, needs more complex changes.

Furthermore, the newts themselves aren’t actually immune to their own TTX, they just have an extremely high resistance to it. They can only produce a certain amount in their bodies before they cause their own demise.

Whilst resistant snakes can in theory gobble up as many newts as they can handle, a side-effect of increased resistance is that the snakes travel more slowly. This means the snakes are more vulnerable to their own predators, such as snapping turtles and hawks. This potentially could cause lower resistance to be selected for again, finding some balance between being able to eat the newts and preventing themselves from being eaten. Theoretically, this could make lower toxicities in newts effective again, but it would need many years of research to confirm if this scenario would occur.

What’s next?

There are several ways this research could be used. Other potentially resistant species could be looked at to see if resistance to TTX was developed in the same way as it was in garter snakes. It has been claimed that some species of birds have been seen to eat the newt and survive.

Traits like toxin resistance, that are controlled by more than one gene, are generally hard to study. But this research helps provide a basis for investigating how these traits might develop and how they affect the ecology of an animal. One of the researchers, Joel McGlothlin said that this step by step evolution of resistance in the garter snakes “can be used as a model for understanding complex adaptations that involve more than one gene.”

It is also hoped that this kind of research could be used to help look into epilepsy and other illnesses that involve a reduced function of sodium channels, applying the knowledge gained of how they are blocked by TTX. Therefore, this battle between newts and garter snakes is an interesting area of study, and can be developed to increase our understanding of sodium channel function and the development of important ecological traits.


McGlothlin, J. W., Kobiela, M. E., Feldman, C. R., Castoe, T. A., Geffeney, S. L., Hanifin, C. T., … & Pfrender, M. E. (2016). Historical Contingency in a Multigene Family Facilitates Adaptive Evolution of Toxin Resistance. Current Biology. DOI: 10.1016/j.cub.2016.04.056


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