
Variations in temperature and diet can affect this rodent’s ability to survive venomous snake bites

The power of a snake’s venom to incapacitate its prey may depend on more than just its potency, or even the prey’s tolerance for the toxin. According to a new study published in Biology Letters, it also depends a bit on the weather.
“Even across different populations of the same snake species, eating the same prey, we see evolutionary differences in their venoms,” says Matthew Holding, Ph.D., an evolutionary biologist in the University of Michigan Life Sciences Institute and lead author of the study. “With this study, we really wanted to dig into what drives these differences in the natural coevolutionary arms races between the snakes and their prey.”
With colleagues from the University of Nevada Reno and University of Utah, Holding analyzed how blood serum samples from wild woodrats responded to rattlesnake venom. As the natural prey of rattlesnakes, woodrats have evolved resistance to the snakes’ venom: they can survive between 500 to 1,000 times the amount of venom that would kill a standard lab mouse. This resistance comes from proteins circulating in the rats’ blood that can neutralize the venom.
For this study, the researchers used serum samples from rats that had been exposed to either warm (29.5°C) or cooler (21°C) temperatures. They found that samples from warm group were better at inhibiting the venom’s activity, compared with samples from the cold group. The results represent the first experimental evidence that a rodent’s environmental temperature can affect the blood-based venom resistance, Holding says.
“These were samples that were drawn in Utah and then frozen, thawed back out, and analyzed at the same room temperature here in Michigan — and we could still see a significant difference between rats from the cold and warm groups,” Holding explains. “That tells us that it’s the actual content of their blood that is changing in response to environmental temperature, and it leads to large differences in the ability of that blood serum to inhibit snake venom.”
In both the temperature and diet tests, there appears to be a physiological trade-off to deal with the various forms of stress to the animal. If the animals are dedicating energy to staying warm or to digesting a toxic diet, they may have less energy available for producing these venom-resistant proteins.
The team also analyzed differences in the serum from woodrats fed basic rat chow compared with those fed more of their natural diet, which consists mainly of a fairly toxic plant called creosote bush. Previous research has demonstrated how woodrats are able to tolerate the near-lethal food. This latest study indicates that consuming the toxic plant may come at a cost, though: The serum from rats that had eaten more creosote was less effective in inhibiting the rattlesnake venom.
“In both the temperature and diet tests, there appears to be a physiological trade-off to deal with the various forms of stress to the animal,” says Denise Dearing, Ph.D., distinguished professor of biological sciences at the University of Utah and senior author of the study. “If the animals are dedicating energy to staying warm or to digesting a toxic diet, they may have less energy available for producing these venom-resistant proteins. And turning on their internal heater to stay warm seems to exert a larger physiological cost in terms of venom resistance.”
The team next hopes to identify which of the hundreds of proteins found in woodrat serum are changing, which may offer more clues about how the animas are able to neutralize rattlesnake venom.
“The study of venoms and the animals that resist them has uncovered some very potent pharmacologically active molecules and has led to the development of medications like anticoagulants and even Ozempic,” Holding says. “I’m really interested in the basic science of how the environment can impact coevolutionary relationships between snakes and their prey from one location to another. But it can also lead to the discovery OF powerful molecules that may have other important applications.”
Top image: Woodrats, the natural prey of rattlesnakes, have evolved resistance to their predator's venom. (Photo credit: Denise Dearing Ph.D.)
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“Ambient temperature and toxic diets constrain snake venom resistance in a desert rodent,” Biology Letters. DOI: 10.1098/rsbl.2025.0068