Chemical Arms Race: Opossum vs. Viper

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The lean, mean, snake-killing machine recently discovered to have been the evolutionary catalyst for rattlers to develop a venomous attack, and not just a noisy defense, is today most often seen as roadkill.

Though its strategy against cars has a long way to go, the Virginia opossum (Didelphis virginiana) has a long history of dodging death while dining on venomous pit vipers. When copperheads and rattlesnakes, for example, bite the opossums, their venom proves ineffective.

Luckily for the marsupial, opossum blood contains a chemical that fights off the worst effects of the venom.

Rapid evolution of both the snake’s venom and the opossum’s venom defense suggest that the two creatures are in a chemical arms race, having evolved in response to each other, according to researchers at the American Museum of Natural History in an article published in PLoS One.

"We've known for years that venom genes evolve rapidly in snakes, but the partner in this arms race was unknown until now. Opossums eat snakes because they can," said Robert Voss, curator in the Department of Mammalogy at the American Museum of Natural History, in a press release.

"Snake venom toxins evolve incredibly rapidly," said Voss.

"Most herpetologists interpret this as evidence that venom in snakes evolves because of interactions with their prey, but if that were true you would see equally rapid evolution in toxin-targeted molecules of prey species, which has not yet been seen. What we've found is that a venom-targeted protein is evolving rapidly in mammals that eat snakes. That suggests that venom has a defensive as well as a trophic role."

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American pit viper venom is mostly hemotoxic, meaning it attacks the blood. One way it does this is by breaking down substances in mammal blood that help it clot. A protein in the opossum, called von Willebrand Factor, seems to have evolved rapidly to improve the animal’s ability to fight off the anti-coagulant effect of viper venom.

"It is so uncommon to find genes under strong positive selection, that the exceptions are really interesting and often conform to one evolutionary circumstance when two organisms are coevolving with each other," said Voss.

"This finding took us by surprise," said Sharon Jansa, associate professor in the Department of Ecology, Evolution and Behavior at the University of Minnesota and a Museum research associate.

"We sequenced several genes—including the one that codes for von Willebrand Factor (vWF)—to use in a study of opossum phylogeny. Once we started to analyze the data, vWF was a real outlier. It was evolving much more rapidly than expected in a group of opossums that also, as it turns out, are resistant to pit-viper venom."

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The ‘possum vs. viper arms race can be observed through the way the animals DNA mutated and evolved. The opossum’s vWF gene showed strong evidence of replacement substitutions. Replacement substitutions occur when a short section of the DNA code is replaced by a different bit of code and results in a change of the amino acid coded for by the DNA.

Many substitutions have no effect, and are called silent substitutions. Silent substitutions don’t influence evolution much. But a large number of replacement substitutions often relates to rapid evolution.

"Most nucleotide substitutions have little or no effect on protein function, but that doesn't seem to be the case with vWF in these venom-resistant opossums," said Jansa. "The specific amino acids in vWF that interact with toxin proteins show unexpectedly high rates of replacement substitutions. These substitutions undoubtedly affect protein function, suggesting that the vWF protein can no longer be attacked by these snake toxins."

IMAGE 1: A rattlesnake and a copperhead. (Wikimedia Commons)

IMAGE 2: The Virginia opossum (Wikimedia Commons)

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