NORMAN, Okla.—Snakes have been around for some 150 million years, but their ancient physiology might hold some important clues to developing new drugs.

Aside from their sleek exteriors, snakes' internal physiology is perhaps even more intriguing. "It's a really fun model for studying the extremes of adaptation," Todd Castoe, a researcher at the University of Colorado (CU) School of Medicine's biochemistry and molecular genetics department, said June 20 at the Evolution 2011 annual conference in Norman, Okla. In addition to the wow-factor of deciphering the snakes' interesting innards, the strange systems could help us better understand our own biology.

As infrequent feeders, snakes have a highly variable metabolism, which can dip down to one of the lowest-known rates of any vertebrate. In particular, "the Burmese python is the quintessential model of the extreme version of this," Castoe said. They can increase and decrease their metabolism by some 44-fold and their heart size by more than 50 percent depending on their energy demands.

Behind all of these unusual evolutionary assets are the genes that make these feats possible. However, even as new genetic sequencing technology has allowed researchers to amass an impressive collection of plant and animal genomes, "reptiles have been really over looked by the bulk of sequencing," Castoe noted.

Earlier this year he and his colleagues published the first draft of a snake genomethe Burmese python (Python molurus bivittatus)—and it has divulged some interesting details about this species' agile metabolism. The snake's mitochondria, which are in charge of energy use in cells, "have undergone the single most extensive change that we're aware of," Castoe said.

To learn more about how the Burmese python heart undergoes such vast changes, Castoe and his team looked specifically at cardiac gene expression. Over the 72-hour metabolic cycle, they found many rapid changes in gene expression in the heart. In just a 24-hour sample, there were 1,852 unique transcriptomes (expressed RNAs in the tissue)—261 of which were up-regulated more than five fold.

These changes might help shed light on human heart development and disease. "We're pretty excited to not look at this in a vacuum," Castoe said. Some heart growth in humans is a good thing, such as that which occurs in childhood and due to exercise—what Castoe calls "Lance Armstrong-style heart growth." But other heart enlargement, such as that caused by heart disease, cardiac hypertrophy, is a definite negative and the target of much drug development.

"If we are able to understand the genetic cues involved in rapid python heart muscle increases and decreases, that to be says there is the potential to develop therapeutics for humans," Leslie Leinwand, director of CU Boulder's Cardiovascular Institute, said in a prepared statement in 2008, before the genome had been completed.

More work remains to be done before these new findings can be translated into potential drugs for heart disease in humans. And as researchers digest more of these big snakes' genome, more medical applications might also emerge.

A second and more thoroughly annotated draft of the python genome is expected out this fall. And other snakes are set to join the ranks of the sequenced, including the garter snake, the rattlesnake and the king cobra. Castoe notes that the field only keeps getting more interesting, adding: "If you're not studying snakes already, you should start."

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Image courtesy of Wikimedia Commons/And0283