Woodrats, weighing less than half a pound, possess a remarkable ability to survive venomous rattlesnake bites that could incapacitate or even prove fatal to a full-grown human. New research from the University of Michigan has shed light on this phenomenon, revealing that these tiny rodents, also known as packrats, have developed potent immunity by accumulating extra copies of specific genes.
The study, published in the journal Molecular Biology and Evolution, focused on a group of genes known as SERPINs, which encode proteins that inhibit a common component of snake venom. While previous research highlighted the role of the SERPINA1 gene in neutralizing European rattlesnake venom, the current study delves into the lesser-known SERPINA3 gene.
Unraveling the Genetic Basis of Venom Resistance
“We wanted to see if we could determine a genetic basis underlying this venom resistance,” explained Matthew Holding, an evolutionary biologist at the U-M Life Sciences Institute. “We noticed that, whereas humans have only one SERPINA3 gene, these rats have 12 copies. They each encode a slightly different protein, and we have no idea what any of them do.”
This research, supported by the National Institutes of Health and the University of Michigan’s Honors Summer Fellowship, identified that the dozen SERPINA3 genes in woodrats emerged through a process called tandem duplication. This process involves the insertion of an extra gene copy into the genome during development, allowing the original gene to maintain its function while the new copy evolves to potentially encode a different protein with a novel function.
Evolutionary Arms Race: Snakes and Their Prey
Tandem duplications are not exclusive to woodrats; they are frequently observed in snake venom. As prey species develop resistance to venom, snakes evolve new proteins to maintain their toxicity. The research team speculated that genetic changes in snake venom might be driving the duplication and diversification of SERPINA3 genes in woodrats.
Meilyn Ward, a former undergraduate student in the Ginsburg lab who co-led the study with Holding, conducted tests on the proteins produced by each of the 12 woodrat SERPINA3 genes against venom samples collected from rattlesnakes. The findings revealed that many SERPINA3 proteins directly bound to venom components, neutralizing their toxic effects.
“Our findings brought SERPINA3 proteins into the conversation about venom resistance,” said Ward, now a medical student at Duke University. “Previous work in this area had focused mainly on SERPINA1, and we now know that these duplicate SERPINA3 genes are an important factor in the coevolution between woodrats and their predators.”
Implications for Understanding Venom Resistance
The research team also observed significant variation in the activities of different SERPINA3 proteins. While some proteins did not interact with the venom, suggesting alternative roles in woodrat survival, others inhibited multiple venom components simultaneously, highlighting the complexity of this evolutionary adaptation.
Holding emphasized the broader implications of the study, noting that gene duplication could be one of many factors contributing to venom resistance. “It uncovers one more tool in the rodents’ toolbox that can be studied across other animals as part of this larger question of how to survive venomous snakebites,” he said.
In addition to Holding and Ward, the study’s authors include Laura Haynes and David Ginsburg from the University of Michigan, Mark Margres from the University of South Florida, and Marjorie Matocq from the University of Nevada Reno.
This discovery not only enhances our understanding of the genetic mechanisms underlying venom resistance but also opens new avenues for research into similar adaptations in other species. As scientists continue to explore these genetic defenses, the findings could inform the development of new treatments for venomous bites in humans and other animals.
