Which Came First: The Opossum or The Snake?

by Katie Pratt

The other day I was idly perusing the science and nature section on Netflix, trying to decide between people, animals, or dramatic landscapes. I settled on National Geographic’s Australia’s Deadly Dozen, and less than an hour later was utterly terrified of the continent. There are a gajillion venomous beasties there! Spiders, octopuses, fish, in the water, on land, in the wood shed, in your laundry, everywhere. And these things don’t mess around; their venoms usually kill within hours unless you get your bitten self to the ER in time to receive anti-venom (N.B. not available all colors or sizes).

Some of the nastiest tails were about snake venom, which is a powerful cocktail of anti-coagulants and metabolic poisons. The show’s narrator relished the opportunity to explain the effects of snake venom, which often include paralysis and massive internal bleeding.

But some animals attack and eat venomous snakes (for example, the mongoose and the badass honey badger). Not only do these predators ignore debilitating snakebites, they eat a massive amount of the venom in their serpentine meal. At the molecular level, there are three potential ways in which venom-resistance could manifest: 1. The organism lacks the venom target, 2. The resistant animal possesses some kind of neutralizing factor in its blood, or 3. The venom target is modified in such a way that it is no longer vulnerable. The first mechanism has long been ruled out, as snake venoms select essential physiological targets, however many examples exist for mechanism number two.

In a paper published recently in PLoS ONE Sharon Jansa and Robert Voss (from The University of Minnesota and the American Museum of Natural History in New York, respectively) use their evolutionary biology skills to shed some light on the third mechanism. While co-evolution of venom and resistance has often been described as a kind of “arms race”, where an alteration in venom structure is quickly recognized and accommodated for by the target species, it has never actually been observed. Until now!

Green Pit Viper. Unless you're an opossum or honey badger, this should scare the crap out of you.

Jansa and Voss used the relationship between opossums and pitvipers in their study. Various opossum species in the Didelphis, Lutreolina, and Philander genuses are resistant to pitviper (a family of snakes that include rattlesnakes) venom, not only because they inhabit the same environments (predominantly in south America), but also because pitvipers make up a huge chunk of the opossum’s diet.

Pitviper venom contains, amongst other nasties, C-type lectin-like proteins (CLPs) that target von Willebrand Factor (vWF), a critical protein in the blood-clotting process. Crucially for this study, the region of vWF recognized and bound by CLPs has been mapped in detail, and the exact amino acid residues needed for them to be effective are known. Since no CLP-neutralizing factors have been identified, the authors looked for amino acid changes in vWF that could explain decreased venom potency. Sure enough, they found that there had been strong positive selection for amino acid substitutions that altered the hydrophobicity of the site on vWF recognized by CLPs.

Perhaps the most interesting piece of brain candy in this paper is in differentiating between the hunter and the hunted. While there is clearly an “arms race” going on, who is the aggressor? Snake venom evolved as a way to stun and kill prey, but when the snake is prey, the venom becomes a way of exacting revenge on the animal ballsy enough to eat it. So then are the venom-resistant mutations in the opossum due to extensive snake-eating, or defense against a venomous aggressor? I feel like I am tying my neurons in knots…either way, this is a fascinating example of rapid and specific co-evolution.

Oh and don’t worry, after the initial shock wore off, I continued making plans to take a trip down under!

Katie Pratt is a graduate student in Molecular Biology at Brown University. She has a passion for science communication, and in an attempt to bring hardcore biology and medicine to everyone, she blogs jargon-free at www.katiephd.com. Follow her escapades in the lab and online on Twitter.

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