Tiger snake. Image Courtesy Steward Macdonald.

Being bitten by an Australian tiger snake is a wholly unpleasant experience. Within minutes, you start to feel pain in your neck and lower extremities—symptoms that are soon followed by tingling sensations, numbness, and profuse sweating. Breathing starts to become difficult, paralysis sets in, and if left untreated, you’ll probably die. Remarkably, the venom responsible for these horrifying symptoms has remained the same for 10 million years—the result of a fortuitous mutation that makes it practically impossible for evolution to find a counter-solution.


Typically, predator/prey relationships instigate evolutionary arms races in which rival species continually adapt to each other’s tactics over time. Classic examples of these adaptations and counter-adaptations include increasing speed among cheetahs and Thomson’s gazelles, hypersonic hearing among bats and moths (where moths have learned to evade echolocating bats), and any number of animals—both predators and prey—who have had to evolve an immunity to various venoms and poisons.

But as an intriguing new study published in Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology points out that evolution has had to throw in the towel in its efforts to counter the deadly effects of tiger snake venom. New research conducted by Associate Professor Bryan Fry from the University of Queensland School of Biological Sciences shows that tiger snake venom hasn’t changed in over 10 million years, and that’s because it hasn’t had to. Surprisingly, however, this discovery could have a medical benefit for humans.


The secret to tiger snake venom has to do with its biological target—a clotting protein called prothrombin. This critically important protein is responsible for healthy blood clotting, and it exists across a diverse array of animal species (humans included). Any changes to this protein and the way it works can be catastrophic to an animal, leading to life-threatening conditions such as hemophilia. It’s this vulnerable target that makes the tiger venom so potent, but at the same time, animals are under intense evolutionary pressure to maintain prothrombin in its default, functional state. As Fry explained in a release, if the animals had any variation in their blood clotting proteins, “they would die because they would not be able to stop bleeding.”

But as Charles Darwin pointed out over 150 years ago, evolution tends to thrive on variability, where only the “fittest” survive. In the case of prothrombin, however, any variability (i.e. a genetic tweak arising from random mutation) simply won’t work; the protein must stay exactly as it is, or the clotting cascade breaks down. That’s why prothrombin exists across so many species (i.e. it’s a trait that’s conserved by evolution)—and why no species has been able to evolve a natural immune response to the tiger snake’s poison.

For the study, Fry analyzed the venom of 16 tiger snake populations across all of Australia. It’s the most comprehensive analysis ever conducted of this family of snakes, and it’s overturned a longstanding assumption about venom evolution.

“A long-held belief is that snake venom varies with diet—that is, as the snakes evolve into new species and specialize on new prey, the venom changes along with it,” noted Fry. “Our research has shown that tiger snakes and their close relatives have toxins that are almost identical, despite this group of snakes being almost 10 million years old. We worked out the reason was [sic] that the toxins target a part of the blood clotting cascade that is almost identical across all animals. So we have a new addition to the theory of venom evolution; that when the target [prothrombin] itself is under extreme negative selection pressure against change, then the toxins themselves are under similar such pressure [to also not change].”


The stubbornness of this venom to resist evolutionary change, however, may be of benefit to humans. This discovery explains why tiger snake antivenom is so useful in treatments against bites from other Australian snakes which affect blood in the same way. Tiger snake antivenom has an extraordinary level of “cross reactivity” against other snake species, meaning it can neutralize the lethal effects of venomous bites in many other cases.

“No other antivenom in the world is so spectacularly effective against such a wide range of snakes this way and now we know why,” explained Fry.


[Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology]