As poison frogs go, you are what you eat ...

DALLAS — Some of the world's best chemists will never be honored with a Nobel Prize. They are the tiny, jewel-colored poison frogs of Central and South America.

These frogs have figured out how to produce nearly 600 complicated chemicals in their skin. Some of the poisons are relatively mild, just enough to give a bird or a snake incentive to drop a frog it may have picked up for dinner. Other toxins are so potent that hunters used to rub the tips of blow darts against frogs to better bring down prey.

New research has revealed that at least three frog species can modify their poison into a more lethal form. In a further surprise, biologists have discovered that poison frogs evolved their bright warning coloration at least four times in the evolutionary past.

"It's not just something that happened once in these frogs, but it seems to be going on and on," says David Cannatella, a herpetologist at the University of Texas at Austin.

He and graduate student Juan Carlos Santos recently used DNA to draw a new family tree of the poison frogs known as dendrobatids. The research has shown, in part, how some species that had been thought related to each other really aren't.

"We can reclassify the frogs in a more accurate way," says Santos, lead author of a study that appeared online this month in the Proceedings of the National Academy of Sciences.

The question of how poison frogs got their colors has fascinated biologists since Charles Darwin. Ordinarily, bright colors would draw far too much unwanted attention from a predator. But poison frogs apparently flaunt their colors as a way to show that they taste bad.

"If you imagine the first brightly colored member of a population, it's going to get attacked," says poison-frog specialist Kyle Summers.

That first suicidal frog could be taking the hit for several reasons, he explains. It might be sacrificing itself so that others of its species would be protected in the future. Or the coloration could be a purely selfish act, a way to keep from getting bitten again.

Animals' use of colors as warning signals is called aposematism, and biologists had thought it such an unusual trait that it would have evolved only once among poison frogs. But that's not what Cannatella's group found when it started looking at frog DNA.

The project, now based in Austin, arose in Quito, Ecuador, when Santos was an undergraduate student working with biologist Luis Coloma of the Pontificia Universidad Catolica del Ecuador. Santos wanted to study how the different dendrobatid frogs were related to each other. So off he went into the field.

In hillsides, pastures, forests and more, Santos collected dozens of species of dendrobatids. Fortunately, they weren't hard to find.

"It's kind of striking because you just see these red things hopping around," he says.

More challenging were the "cryptic," or camouflage-colored, poison frogs. These may make up half or more of all poison-frog species, yet little is known about them because they're not as visually striking.

Armed with their new amphibian collection, Santos and Coloma approached University of Texas' Cannatella. Together they ran DNA analyses and pieced together a new family tree.

The results had them nearly hopping with surprise. Some of the most colorful species turned out to be more closely related to the cryptic frogs than to each other. Previously, biologists had thought that the brightly colored frogs had evolved from the more primitive cryptic ancestors.

By analyzing the family tree, the researchers discovered that aposematism had arisen several times over millions of years of frog history. That suggests that it's not as difficult to evolve as scientists had thought.

Some poison frogs are more poisonous than others, but they all get their toxins from the same place — their diet of ants, mites, millipedes and other arthropods, which are rich in alkaloid chemicals. The frogs take the poison from their dinner and put it into their skin.

Ironically, the frogs' poison may have unmatched medicinal value. For instance, the frog chemical epibatidine turned out to be 200 times more potent a painkiller than morphine.

By studying the toxicity of frogs over time, John Daly of the National Institutes of Health has made some startling discoveries about the complex interplay between diet and poison. One frog species that wasn't very poisonous when sampled in the 1970s, for instance, had become quite toxic by the time it was re-studied in the 1990s, he says. The frog must have begun eating alkaloid-rich millipedes instead of its ordinary, nontoxic food.

"As man has disturbed the habitat, this millipede has become a source of food for the frogs," he says.

In fact, biologists are racing to study the poison frogs before many of the species disappear. Habitat destruction, fungal infections and other threats are affecting frogs worldwide.

Santos discovered this while frog-hunting in Ecuador.

"Sometimes it's pretty sad," he says, "because you go where people used to say there were tons of frogs and you find nothing."