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Roy Wood/U.S. Geological Survey

How Snakes Got Their Extreme Makeovers

When two groups of scientists decided to sequence a snake genome, both figured they might as well pick one of the most extreme species. One group chose the king cobra, the largest venomous snake in the world and one of the most deadly ones. The other went for the Burmese python, a species that lacks venom but has remarkable eating habits: It strangles its prey to death and can survive on just three to five meals a year.

Now, both groups have published their analysis of the genomes, and their findings reveal the molecular basis behind these snakes’ remarkable traits. The Burmese python’s genome allows it to rev up its metabolism to 40 times its usual rate after it eats, during which organs like the kidney, liver, and gut can double in size in less than 3 days. In the cobra’s genome, entire gene families were repurposed to help produce a sophisticated, highly toxic mix of proteins and peptides that kept changing as prey evolved mechanisms to elude it. Both papers, published online today in the Proceedings of the National Academy of Sciences, show that snakes have evolved very rapidly.

These are only the first two snake genomes ever sequenced; snake scientists have studied snakes around the world, but were late to join the revolution in molecular biology, says Nicholas Casewell, a snake scientist at Bangor University in the United Kingdom and a co-author on the king cobra paper.

The team that sequenced the python genome, led by Todd Castoe of the University of Texas, Arlington, zoomed in on the changes that happen in the Burmese python—which lives in Southeast Asia and recently invaded the Florida Everglades—after it eats. The researchers checked the activity of genes in the heart, kidney, small intestine, and liver before a meal and again 1 and 4 days after eating. “The magnitude of the gene expression response really floored us,” Castoe says. Half the python’s genes changed their activity significantly within 48 hours, the team reports in its paper.

With the study in hand, “people are going to have a ton of new targets for looking at the genomics” of how snakes adapt physiologically, predicts Harvard University evolutionary biologist Scott Edwards.

The team also compared the 7442 genes found as single copies in both the cobra and the python with the same genes in all other land vertebrates sequenced so far. The bottom line: Snake genomes have changed a lot—and they have changed very fast to meet the demands of their unusual lifestyles.

The scientists who sequenced the king cobra—which occurs in India, China, and Southeast Asia—focused on its venom, a very toxic mix of 73 peptides and proteins. They measured gene activity in the venom gland and in the so-called accessory gland, a poorly understood structure through which the venom passes before it leaves the cobra’s mouth.

In the paper, the researchers report that the two glands have very different gene activity patterns. The accessory gland doesn’t produce toxins but makes many different lectins, a group of proteins that bind carbohydrates. In some other snake venoms, toxic lectins are part of the mix, but in the cobra, lectins are never released into the venom. The accessory gland's role may be to activate the venom somehow, but “we really don’t know” what lectins do exactly, Casewell says.

The venom gland itself relies on 20 gene families for its toxins. The scientists found that the genes for each toxin family were also used in other parts of the body in the snake's evolutionary past and even today. “These dangerous proteins are co-opted from elsewhere in the body and [are] turned into weapons and diversified,” says Frank Burbrink, an evolutionary biologist at the City University of New York. Often, a gene was copied more than once, allowing each copy to mutate in different ways, yielding an ever more sophisticated mix.

That gives the snake an advantage in an evolutionary arms race. The cobra’s prey evolve constantly as well, developing ways to resist being immobilized or killed by the toxins. For snakes, this genetic competition can be deadly, because ineffective venom can enable potential prey to turn on the snake and kill it.

The paper is "a stunning piece of work, just amazing," says Jimmy McGuire, an evolutionary biologist at the University of California, Berkeley. Vonk, Castoe, and their colleagues stress that they have only just begun to milk their data. And another 10 snake genomes or so are likely to come out within the next couple of years, Casewell says.

Check out the 6 December print issue of Science for a news package on snakes, including more on the genomes, a story about efforts to develop drugs from venom, and a report about the fight against the invasive brown tree snake in Guam.