A genetic adaptation makes certain squirrels and hamsters immune to the cold
You step outside of your building, bundled up in four different layers and a marshmallow coat. Buried beneath scarves, hats, and gloves, it’s still not enough to keep the cold out. Your face stings from the biting wind, and you can feel icicles forming on your nose. There’s snow melting in your boots and you’ve long since lost the ability to feel your hands. You feel like you’ll never be warm again. While we may cower in the face of cold weather, for some animals, the cold is no big deal. In fact, they don’t even feel it.
A team of researchers at Yale led by Elena Gracheva and Sviatoslav Bagriantsev are currently investigating a molecular adaptation in the Syrian hamster and a species of squirrel native to North America, called the thirteen-lined ground squirrel, that enables them to endure harsh winters. The body temperatures of these rodents adjust to match the air around them, enabling them to hibernate for months in temperatures just above freezing without noticing the gruelling winter.
Bring on the Cold
The root cause of this ability comes down to genetics. “Being sensitive to the cold would prevent the rodents from hibernating, much like how being cold would prevent us from sleeping,” Gracheva said. Therefore, there must be some quirk in their DNA that allows them to withstand the extreme cold for such extended periods of time.
In behavioral studies performed on the rodents, the researchers found that when given the choice between two plates of different temperatures, the squirrels and the hamsters did not avoid the cold as strongly as mice did. This suggests that there are genetic differences among rodents that allow some species to endure the cold but not others. This diminished sensitivity to the cold could be caused by a number of different factors such as a reduced ability to perceive cold in the nerves responsible for registering temperature, known as somatosensory nerves, or a suppression of the instinct to avoid cold in the central nervous system of certain rodents.
A Cold-Sensing Protein
In a study published in Cell Reports, Gracheva and her colleagues found that by imaging the somatosensory neurons of the rodents, they were able to isolate the adaptation to a specific protein called TRPM8. TRPM8 is an ion channel, which is a type of protein found in a cell’s membrane that allow specific charged atoms or molecules to pass through. Many ion channels open and close in response to certain stimuli in order change the electric potential of the cellular membrane, and thus are particularly important in allowing nerve cells to relay electrical signals to the brain. Specifically, TRPM8 is a cold-activated ion channel—when the temperature decreases, this channel opens and excites neurons, leading to generation of electrical signals that are transmitted throughout the rodents’ nervous system. “The neuron then sends electric impulses to signal to the brain that cold temperature has been encountered,” Bagriantsev said.
Something different in the TRPM8 of the thirteen-lined ground squirrels and Syrian hamsters makes the protein insensitive to the cold. Upon isolating the protein, the researchers were able to identify the adaptation in a specific group of six amino acids, the building blocks of proteins, that are the difference between cold sensitive and cold insensitive organisms. Although the scientists do not know exactly when the hibernators developed this adaptation evolutionarily, they do know that the squirrels and the hamsters developed it independently. “They use different structural elements at the molecular level but arrive at the same end product, which is cold-insensitive ion channels,” Gracheva said.
Because the adaptations were developed independently, there are slight differences in temperature reactions between the two species. Specifically, hamsters are slightly more sensitive to the cold than the squirrels. However, when compared to species without the adaptation, such as the mice, these differences are negligible. In a previous report published by the lab, researchers found that the thirteen-lined ground squirrel is also extremely resistant to heat, enabling it to survive in harsh climates such as deserts, though this ability stems from an adaptation in a protein other than TRPM8.
Now that the exact adaptation has been located, the researchers are working to reintroduce cold sensitivity into the TRPM8 of the squirrels and hamsters by substituting their key amino acids for the ones found in the mice. The researchers are also attempting the opposite—inserting genetic substitutions into the mice to see if they can become cold-insensitive.
Through this research, the team has taken significant steps towards a better understanding of the hibernation puzzle. Scientists still do not fully understand what induces hibernation among certain species and how it is possible biologically. For example, little is understood about what causes heart rates to slow down, how these species go months without consuming nutrients or water, or how the animals do not lose bone mass during this time of inactivity. TRPM8 is one piece to the puzzle. The genetic adaptation explains how certain hibernating species can sleep through extremely cold temperatures. However, it is not that TRPM8 becomes cold-insensitive specifically for the hibernation period. Rather, the adaptation is encoded in their DNA such that they have this cold-insensitivity from birth. “We still don’t know everything about what causes hibernation,” Gracheva said. “It’s possible that certain genes do turn on when the rodents enter this state but TRPM8 is not specifically related to hibernation. It is cold-insensitive all the time.”
In addition to studying hibernation, the group also plans to investigate whether cold-insensitive rodents can adapt to temperatures below ten degrees Celsius. The group’s goal is to the test the limit of the animals’ tolerance, as well as to try to understand how these animals ward off hypothermia.
Potential Human Applications
Don’t put away your jackets yet though, because even though the researchers are working on replicating the cold-insensitivity in mice, there’s a long way to go before we could even think about substituting the adaptation into humans.
But there are other ways this research applies to humans—specifically in the field of medicine. For example, one major detriment to chemotherapy is that patients often develop an extreme aversion to even mild cold. It is possible that this research could be used to minimize these effects and help patients be able to better tolerate the cold.
“This study furthers our understanding of how vertebrates, including humans, feel cold. It will help develop approaches toward better organ preservation and contribute to the development of novel techniques for lowering human body temperature, which is required during some medical procedures and may be useful for long-time space travel,” Bagriantsev said.
So good luck tomorrow on your walk through the bitter February cold. Just remember to channel your inner thirteen-lined ground squirrel.
About the Author
Elizabeth Ruddy is a Sophomore Physics major in Berkeley. She enjoys dancing, writing for the Yale Scientific, and hibernating.
The author would like to thank Professor Gracheva and Professor Bagriantsev for sharing their time for this article.
 Thirteen-lined ground squirrels have adapted to become less sensitive to the extreme cold than other mammals. Cred: Elena Gracheva
 The Syrian hamster has also demonstrated a marked tolerance for the cold. Cred: wikimedia
 Graphical abstract of the difference between the cold-insensitive rodents and the control group of mice. Cred: Elena Gracheva