In high school biology, you learned that co-evolution was an arms race. Gazelles speed up to escape cheetahs, who grow ever-swifter as the generations pass. Crabs grow more powerful claws to puncture snails’ thicker and thicker shells. Every living thing on Earth is engaged in a battle to become bigger, safer, deadlier, smarter, faster, harder to track and more difficult to evade.

But evolution is not always an all-out war. Sometimes it's more subtle — an ever-evolving negotiation between two species that are constantly sizing up one another, seeking out vulnerabilities and adjusting their strategies in response to what they find. It’s diplomatic. Except instead of concluding with peace, these negotiations end when one animal eats the other. (Let’s not share this metaphor with anyone at the United Nations.)

Take, for example, the rattlesnakes and squirrels of northern California, combatants in a notoriously bitter conflict that has raged over centuries. Each species is armed to the teeth (literally). Squirrels team up to mob their rattlesnake predators, ward them off with bushy tails, and even chew up snake skin and rub it on their fur to confuse snakes trying to sniff them out (which is so meta). Snakes, meanwhile, perfect stealthy slithers and possess heat-sensing pits on their faces, not to mention incredibly toxic venom.

But, as is fitting for a savvy snake, a rattler uses its chief weapon as a scalpel, not a sledgehammer. A study published this week in the journal Proceedings of the Royal Society B found that California rattlesnakes’ venom is carefully calibrated to overcome the specific defenses raised by the squirrels in their region. As a result, the venom varies measurably from county to county, possibly even from one highway exit to the next. California snake venom is kind of like wine — it comes in regional varieties. None of which you want to be drinking.

The battle starts at birth, when squirrels begin creating anti-venom proteins that they pump into their blood stream, arming themselves for the day when a rattlesnake attacks. These proteins vary based on the environment — altitude, annual rainfall, type of vegetation — and on the venom of the snakes that live in the region.

In response, the snakes are constantly tweaking the composition of their own venom, working on ways to overcome those defenses.

“It’s like a lock and a key,” said Matthew Holding, an evolutionary ecologist at Ohio State University and the lead author of the study. “Resistance is a lock and venom is the key and I have to have the right key to open the door.”

This process isn’t a conscious one; it’s a product of natural selection. Squirrels with inadequate defenses get eaten before they can pass their wimpy genes down to their children. Likewise, snakes with unsuitable venom starve to death before they can reproduce. Those that do live are the ones best suited for battle.

And at the moment, the snakes seem to have the upper hand, Holding said. When he and his colleagues tested 12 venoms from 12 different regions against 12 squirrel blood samples from those same areas, the venoms usually beat out the blood from their same region. These fights were staged in test tubes, but it’s simple to imagine what they mean for the real world: lots of dead squirrels.

That’s surprising, Holding said, because most theories of evolutionary biology predict that prey’s defenses should be marginally better than their predator’s weapons. Prey, after all, have more to lose.

“It’s a longstanding idea called the Life-Dinner principle,” Holding said. “If the predator loses in a given contest it just misses a meal. But if the prey loses it dies.”

Natural selection should work more intensely on those that avoid dying than ones who simply manage to get dinner, he continued. But the snake venom study suggests that something more complex may go down when two species co-evolve.

It’s important that we understand how this works — and not just because it’s interesting to evolutionary biologists (or because we feel bad for squirrels). Venomous snakes bite several thousand people a year in the United States, and every year a few of those people die. Doctors, pharmaceutical companies and ophidiophobes would all like to know more about variation in snake venom and ways of protecting against it.

“It’s a complex and fascinating system with lots of other questions to ask,” Holding said. 

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