After getting bit by a bat bug at a recent conference, Armin Scheben had a literal and figurative itch to study bats. The blood-sucking insect is one of many disease-causing parasites that latch themselves onto the flying mammals—yet, bats rarely get sick in the same way humans do.
Mammalian immune systems evolve fast as species are always challenged with new pathogens in their environment. “You need to constantly keep pace with new bad guys that are trying to infect and hurt you,” says Scheben, who is a postdoctoral fellow in population genomics at Cold Spring Harbor Laboratory (and has since recovered from the bite). And while he has studied the genetic adaptations of several mammals, they pale in comparison to the ones that have given bats the ability to fight off infections so effectively.
In a new study published today in the journal Genome Biology and Evolution, Scheben and his team have identified the genes that have contributed to bats’ rapidly evolving immune system and their unique ability to evade deadly viruses and even cancer. Understanding how bats survive diseases could inspire new immune treatments for humans and potentially help prevent another pandemic.
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The authors analyzed the DNA of 15 different bat species to get a clearer picture of how their genes evolved over time. They fully sequenced the genomes of two bat species, the Jamaican fruit bat and the Mesoamerican mustached bat, and gathered the other species from preexisting datasets.
They then compared the bat genomes to that of humans, mice, and other cancer-susceptible mammals, focusing their attention on the sequences that encode proteins responsible for causing or preventing diseases. To start, they lined up the homologous genes, or shared genes among different species inherited from a shared evolutionary ancestor. (It’s like comparing apples with apples, explains Scheben.) With each homologous gene, they hypothesized two scenarios: if bats lost it or if it mutated. If the flying mammals completely lost the gene, it suggests that the omission is important in fighting disease. But if it remained with subtle changes in the DNA sequence that are only found in bats, it could show a change in gene function that somehow helps the group stay healthy.
In the end, the most striking changes the team detected were in type one interferon (IFN) genes, which are important for controlling inflammatory responses to infections. Specifically, they observed a shift in the number of antiviral IFN-α and IFN-ω genes. For instance, three bat species seemed to have lost all of their IFN-α while increasing the number of IFN-ω genes.
According to Scheben, the most surprising finding was observing the loss of IFN-α and addition of more IFN-ω genes, “which hadn’t been reported at all before.” The results suggest the new IFN-ω and missing IFN-α genes are important in bats for resisting viral infections while preventing overactive inflammatory responses—a feature that has made inflammation a double-edged sword in humans.
But while the findings have put geneticists one step closer to understanding how bats evolved their unique ability to resist cancer and viruses, it doesn’t paint a complete picture. The study focuses only on the genetics of innate immunity (the immediate immune response to infected cells), says Tony Schountz, a professor at the Center of Vector-Borne Infectious Diseases at Colorado State University, who was not involved in the study. It does not include information about bats’ adaptive immunity, which consists of the antibody and T-cell responses that many mammals use to fight diseases. “These are two very different, but complementary components of immunity,“ Schountz explains. “Nearly all of the focus on bat immunity to date has been on innate immunity, principally because the study of adaptive immunity requires live animals, which few groups have and is much more complicated.”
Even without a full set of information, understanding the changes in the bats’ innate immune system could help scientists develop genetic treatments for humans that decrease susceptibility to certain illnesses. We can also learn which genes drive bats’ 20- to 30-year lifespans, or how their bodies have adapted to process sugar-rich foods without developing the negative consequences seen in people with diabetes.
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And though bats have gained a notorious reputation for their purported role in spreading COVID, Scheben hopes that these new findings could point researchers in the right direction in understanding how the animals host such potent viruses and parasites without getting very sick. One day, he says, that information could be used to prevent our species from suffering major symptoms when infected. “It’s absolutely not misplaced to believe that studying bats could help us prevent another pandemic.”