Prof. Edmund D. Brodie, Jr.
The garter snake has evolved a resistance to the normally deadly toxins carried by newts, making them its prey. Researchers say the newt carries enough neurotoxins to kill 50,000 mice or 10 people.

For years, scientists at Utah State University have been documenting a "chemical arms race" between normally toxic newts and the garter snakes that eat them. Now they have discovered the genetic changes that allow the snakes to evolve molecular defenses against the poison.

Garter snakes regularly do something you can't — something that perhaps no other creature but the snakes can do — eat a rough-skinned newt and live. A newt is a member of the salamander order, and rough-skinned newts are common in West Coast streams.

As garter snakes have raised their chemical defenses, the newts have become more deadly. According to USU, one newt (scientific name Taricha granulosa) carries enough neurotoxins of the same type found in Japanese puffer fish to kill 50,000 mice or 10 people.

Shana L. Geffeney, a graduate student at the Logan university, is the lead author of the study published in the most recent edition of the journal "Nature." Her co-authors are Esther Fujimoto, Edmund D. Brodie Jr. and Peter C. Ruben of USU and Edmund D. Brodie III of Indiana University. Fujimoto is now at the University of Utah, says the report.

Their study examined the way genes regulating the cell's sodium channels changed in response to the neurotoxins carried in the newts' skin. Sodium channels are openings that let sodium move in and out of the muscle cells; this movement allows the muscle to contract.

When the toxin attaches to a protein that is part of the channel's structure, sodium can't move in and out and the cell can't move.

Newt poison called tetrodotoxin (TTX) binds onto the protein, paralyzing muscle function. Muscles attached to the victim's bones don't work, and the person or animal unlucky enough to be poisoned by a newt will stop breathing.

The poison is so deadly because it blocks activity in nerve and muscle fiber, said Geffeney.

In a 2002 study in the journal Science, Geffeney, the Brodies (father and son professors) and Ruben showed that the newts and snakes were locked in the arms race. What's new is that they now know the molecular basis for the snake's defense.

The poison binds to a particular place on the protein molecule. In most animals, these proteins are the same, and the poison bonds to an important part of the molecule. From chickens to rats and humans, the sodium channels are vulnerable to TTX. But not in the garter snake.

The snakes' genetic makeup mutated so that the protein was shaped differently. The poison could not bind onto the new shape.

Snake muscles with the modified proteins were able to function even with high doses of the poison, the researchers found.

"We made specific mutations and we showed that the specific mutations altered the ability of the TTX to bind to the protein," she said.

"So we ended up learning more about the shape of the protein," Geffeney was surprised to see changes in such an important part of the protein.

Another discovery was that separated populations of garter snakes differ in their amino acid sequences. In their separate habitats, at least two populations of garter snakes apparently evolved the defenses on their own.

One question the team would like to answer, she said, is "How many times has this elevated level of resistance evolved?"

The elder Brodie, former chairman of USU's Biology Department, said the study has extended the research into the fields of neurobiology and genomics.

"Shana set out to isolate the proteins that form the sodium channel, and could sequence those and determine the mutations that had taken place in those populations that were resistant," he said.

Possibly other populations of garter snakes would show additional changes, he said. "We know that the changes have evolved at least twice independently."

So who's winning the chemical arms race?

"It seems to be sliding back and forth," Brodie said. "The snakes may be ahead for the moment, but it's variable, area to area."


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