How Do Garter Snakes Eat Toxic Newts? An Evolutionary Arms Race

The deadly prey: the rough-skinned newt

The rough-skinned newt (Taricha granulosa) lives in ponds, lakes and damp forests along the Pacific coast of North America, from southeastern Alaska to the Santa Cruz area of California. Its brown back and bright orange belly hide a powerful defense: its skin contains tetrodotoxin (TTX), the same nerve poison famous from pufferfish.

Tetrodotoxin works by plugging voltage-gated sodium channels, tiny pores in nerve and muscle cells that let sodium flow in when a signal fires. With the channels blocked, nerves cannot send signals and muscles stop working. A predator that swallows a toxic newt can become paralyzed and die from respiratory failure. The most toxic newts carry enough TTX to be dangerous to a person if swallowed, and at least one fatal human case is on record from Oregon.

When threatened, a newt arches its body and curls up its tail to show off the orange underside. To most predators, this warning is enough.

How garter snakes resist tetrodotoxin

Most snakes and other vertebrates die after swallowing a highly toxic newt. Yet in parts of the Pacific Northwest and California, the common garter snake routinely eats them.

Starting in the late 1980s, Edmund D. Brodie Jr., his son Edmund D. Brodie III and colleagues measured this resistance in a clever way. They timed snakes crawling along a short racetrack, then gave them a measured dose of TTX and timed them again. Snakes that slowed down only a little were resistant; snakes that stopped were not. Their tests showed huge differences between populations: snakes living with highly toxic newts tolerated doses that would immobilize snakes from other places.

The cause turned out to be molecular. In 2002, Shana Geffeney and colleagues reported in the journal Science that resistant snakes have sodium channels in their skeletal muscles that are less sensitive to TTX. Later work traced this to a few mutations in the gene for the muscle sodium channel, called Nav1.4. The changes sit in the part of the channel where TTX normally binds, so the toxin attaches less firmly and sodium can still flow.

Costs of being resistant

Resistance is not free, and that helps explain why it is not found everywhere:

• Slower snakes. The Brodies found that the most resistant snakes tended to crawl more slowly than less resistant snakes, even without any toxin. Changed sodium channels may make muscles work slightly less well.
• Temporary paralysis. Even resistant snakes can be slowed or immobilized for hours after eating a very toxic newt. A snake lying still and unable to flee is easy prey for hawks and other predators.
• Choosing the right meal. Experiments suggest that garter snakes can reject a newt that is too toxic for them, sometimes taking it into the mouth and then releasing it.

Where newts are only mildly toxic or absent, the costs outweigh the benefits, and resistance stays low.

A geographic mosaic of hot spots and cold spots

The snake-newt arms race does not look the same everywhere. Across the West Coast, biologists have mapped a patchwork, or geographic mosaic, of interactions:

In many places, snake resistance and newt toxicity rise and fall together, which is strong evidence that each species is driving evolution in the other. In some hot spots, snake resistance even seems to have pulled ahead of newt toxicity, so the snakes can eat essentially any newt they meet.

Resistance evolved more than once

Genetic studies show that TTX resistance has evolved independently several times. Different populations of common garter snakes carry different mutations in the same sodium channel gene, and at least two other western garter snake species that eat toxic newts have evolved resistance on their own. Similar changes have also been found in some other animals that eat TTX-bearing prey. When the same molecular solution appears again and again, it shows how strongly natural selection can shape a single gene.

Snakes that become poisonous

There is a final twist. Resistant garter snakes do not destroy all the toxin they eat. They can store tetrodotoxin in their liver for several weeks after a meal, which makes the snake itself poisonous to any bird or mammal that eats it. A garter snake can therefore be mildly venomous through its own saliva and poisonous through its diet; see Are garter snakes venomous? and Is a snake venomous or poisonous? for the difference.

The story of the garter snake and the newt is now a textbook example of coevolution. It links a visible behavior, a snake swallowing a deadly newt, to measurable changes in a single protein and to patterns that stretch across an entire coastline.