Cold Weather Weakens Woodrats’ Snake Venom Defense

For desert woodrats, survival against rattlesnake bites might boil down to something as simple as the weather forecast, according to research published Tuesday in Biology Letters.

Scientists have discovered that these remarkable rodents, known for their impressive resistance to toxins, lose much of their natural immunity to snake venom when temperatures drop – a finding that reveals new complexities in the evolutionary arms race between predator and prey.

The study shows that woodrats maintained in cooler environments (70°F) had significantly weaker venom resistance compared to those kept in warmer conditions (85°F), suggesting that seasonal temperature changes could dramatically affect their survival odds during snake encounters.

“We weren’t really thinking about the effect of temperature on rattlesnake resistance, so we were pretty surprised by the results that there was such a huge effect,” said Denise Dearing, a distinguished professor of biology at the University of Utah and senior author on the study. “In the cooler environments, the rattlesnake venom resistance was really low. And in the warmer environments, it was really high.”

“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,”

Desert woodrats, also called pack rats, have evolved extraordinary resistance to toxins. These unassuming herbivores can survive doses of rattlesnake venom 500 to 1,000 times greater than what would kill a laboratory mouse. This resistance comes from specialized proteins circulating in their blood that neutralize the venom’s deadly components.

The research team analyzed blood samples collected in 2014 from woodrats in southwest Utah. These samples had been drawn after the animals were acclimated to either warm or cool captive environments. Years later, when researchers thawed and tested these samples, the temperature-based difference in venom resistance remained clearly evident.

“We could still see a significant difference between rats from the cold and warm groups,” explained Matthew Holding, an evolutionary biologist at the University of Michigan and lead author of the study. “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 study also revealed another surprising factor that weakens woodrats’ venom resistance: their native diet. When researchers compared woodrats fed standard lab food with those consuming creosote bush – their primary natural food source and itself loaded with toxins – they found that the creosote-eating rats showed reduced ability to neutralize snake venom.

This suggests that woodrats face trade-offs when allocating their body’s resources. Dealing with one type of stress – be it cold temperatures or processing toxic foods – seems to compromise their ability to handle other threats.

“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,” Dearing noted. “And turning on their internal heater to stay warm seems to exert a larger physiological cost in terms of venom resistance.”

The findings provide insight into why rattlesnake venom composition varies across different habitats. Previous research has shown that rattlesnakes produce different venom types depending on where they live, even when preying on the same species.

“Even across different populations of the same snake species, eating the same prey, we see evolutionary differences in their venoms,” said Holding. “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.”

Researchers are now working to identify which specific proteins in woodrat blood change in response to temperature. Uncovering these mechanisms could advance our understanding of venom resistance and potentially lead to new medical applications.

“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.

Beyond potential pharmaceutical applications, the study suggests that changing climate patterns could disrupt the delicate balance of predator-prey relationships that have evolved over millennia. If warming trends continue, rattlesnakes may face more venom-resistant woodrats, potentially triggering evolutionary changes in snake venom composition.

The research team included Alexandra Coconis and Marjorie D. Matocq from the University of Nevada, Reno, and Patrice Kurnath Connors, now an associate professor at Colorado Mesa University, who collected the original samples as part of her doctoral work.

Funded by the National Science Foundation, the study offers a glimpse into how environmental factors shape the ongoing evolutionary battle between predator and prey – a battle where, at least for woodrats, staying warm might be just as important as avoiding fangs.