Study: Ambient temperature and toxic diets constrain snake venom resistance in a
desert rodent (DOI: 10.1098/rsbl.2025.0068)
The power of a snake's venom to incapacitate its prey may depend on more than just its potency or the prey's tolerance for the toxin-it also depends a bit on the weather, says a University of Michigan researcher.
"Even across different populations of the same snake species, eating the same prey, we see evolutionary differences in their venoms," said Matthew Holding, an evolutionary biologist in the University of Michigan Life Sciences Institute and lead author of the study published in Biology Letters.
"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."
Holding and colleagues from the University of Nevada Reno and University of Utah 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 the 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 said.
"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 said. "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."
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," said Denise Dearing, 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 animals 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 said. "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."
This research was funded by the National Science Foundation and the University of Utah. Animal research for this study was approved by the University of Utah Institutional Animal Care and Use Committee and performed in accordance with the institutional guidelines.
In addition to Holding and Dearing, study authors include: Alexandra Coconis and Marjorie Matocq of the University of Nevada Reno, and Patrice Connors of the University of Utah.
Related stories:
-
U-M study uncovers secret color language of snakes
-
Snakes do it faster, better: How a group of scaly, legless lizards hit the evolutionary jackpot
-
Hiss-toric first: U-M museum's 70,000 snake specimens form world's largest research collection
