Evolution of venom, binge eating seen in snake DNA

Snake genes are in high evolutionary gear.

Complete genomes of the Burmese python and king cobra reveal that many snake genes have changed more rapidly than those of other vertebrates, researchers report December 2 in two studies in the Proceedings of the National Academy of Sciences.

The two genomes are the first complete sets of snake genes ever assembled. 

Snakes evolved some extreme survival strategies. Cobras and pythons represent some of the most out-there examples, says David Pollock, a coauthor of both studies who is an evolutionary biologist and genomicist at the University of Colorado School of Medicine in Aurora.

Burmese pythons (Python molurus bivittatus) are ambush predators that seldom find meals. When they do, they gorge. Adult pythons can swallow an adult pig whole. Within four days of consuming such a feast, the snake’s organs expand by at least 35 percent, with some even doubling in size.

“The change in metabolic activity is greater than a racehorse going from standing still to running a quarter-mile race,” Pollock says. After the meal is digested, the organs shrink back to size within days. Pollock and his colleagues determined that this extreme metabolism is coordinated by hundreds of genes.

King cobras, in contrast, rely on venom to take down prey. They are one of the deadliest species of venomous snakes, says Jimmy McGuire, an evolutionary biologist at the University of California, Berkeley. “One is almost certainly toast if bitten by an adult king cobra in a setting where there is no immediate access to antivenin.”  Studying how snake venom evolved may lead to better treatments, he suggests.

The king cobra, Ophiophagus hannah, preys on other snakes and is ideal for studying venom evolution because it must evolve new toxins to take down its victims as prey develop defenses against old toxins.

Michael Richardson, an evolutionary biologist at Leiden University in the Netherlands, and his colleagues discovered that cobras’ venom glands produce a small RNA known as a miR-375, which in other animals is found in the pancreas and the pituitary gland. MicroRNAs help regulate where and when proteins are made. Finding the microRNA in the venom gland may revive an out-of-favor theory that venom glands evolved from the pancreas, though Richardson cautions that the result does not prove evolutionary connection. He thinks that organs such as the pancreas and venom gland both produce miR-375 because they need to secrete proteins.

As for venom components, the researchers discovered that king cobras produce 20 different types of toxins. Many are altered versions of proteins produced elsewhere in the body. The team found that many venom genes started out as duplications of “normal, old, innocent housekeeping genes,” Richardson says. During cobra evolution, those genes in the venom glands rapidly shifted and took on new, deadly properties.

The quick change of nontoxic proteins into venom surprised Scott Edwards, an evolutionary biologist at Harvard University. “Proteins tend to evolve in a very conservative manner,” he says. The rapid change probably reflects strong evolutionary pressure to keep up with and override prey defenses.

The researchers also found a genetic explanation for snakes’ limbless bodies: a missing gene. Snakes have a nearly complete set of Hox genes, which lay out the body plans of a variety of animals. Even though snakes have almost all the genes required to build legs, they lack one called Hoxd12, which scientists previously showed to be important for limb development in four-legged creatures. The gene probably went missing in an early snake ancestor.