Bats are exceptionally long-lived for their body size and can tolerate or control viruses that cause severe disease in other mammals. A major comparative genomics study in Nature now suggests that these two unusual traits may be connected: millions of years of evolutionary conflict with viruses appear to have reshaped immune genes in ways that may also contribute to cancer resistance, DNA-damage control and exceptional longevity.
Researchers generated near-complete genome assemblies and cell lines from eight closely related species of Myotis, one of the largest bat genera. Some Myotis species can live for several decades despite their small size, while closely related species have much shorter lifespans, providing an unusual natural experiment for studying ageing.
The team combined comparative genomics, structural-variation analyses and experiments in primary bat cells to investigate adaptation to viruses, ageing and cancer.
DNA and RNA viruses have shaped bat genomes differently
One of the clearest findings is that bats appear to have evolved different genetic strategies against DNA and RNA viruses. Proteins that interact with DNA viruses showed strong signatures of positive selection, evidence that repeated evolutionary conflicts favoured advantageous changes in host proteins over many generations.
RNA-virus-interacting proteins showed another pattern: they were enriched for copy-number variation, meaning that bats frequently carry different numbers of copies of immune-related genes.
This distinction suggests that viral pressure has shaped the bat immune system through more than one evolutionary mechanism.
PKR reveals an ancient arms race with viruses
The researchers examined one immune factor in particular: EIF2AK2, better known as PKR. PKR is part of the innate antiviral response. It detects double-stranded RNA produced during many viral infections and can inhibit protein synthesis, helping prevent viruses from replicating.
In Myotis, the researchers identified repeated duplications of the PKR gene. Remarkably, some of these different copy-number variants appear to have persisted across species for millions of years.
Such long-lived genetic variation suggests that no single version of PKR provides a permanent evolutionary advantage. Instead, changing viral pressures may continually favour different combinations, evidence of a prolonged host–virus evolutionary arms race.
Viral defence and cancer resistance may be connected
The study then moves beyond infectious disease. Long-lived animals face a theoretical problem: the longer an animal lives, the more cell divisions it experiences and the more opportunities there are for mutations that could lead to cancer. Yet bats show unexpectedly low cancer rates relative to their longevity.
The researchers found that repeated evolution of long lifespan in Myotis was associated with positive selection in pathways involved in cancer biology and cellular stress responses. This raises an intriguing possibility: genes repeatedly modified during evolutionary conflicts with viruses may have broader effects on cellular processes involved in ageing and tumour suppression.
The authors describe this as pleiotropy, when the same genetic adaptation influences several biological traits.
Long-lived bat cells respond differently to DNA damage
The researchers also tested primary cells from the long-lived little brown bat, Myotis lucifugus. When exposed to DNA damage, these cells showed an unusual response compared with cells from shorter-lived mammals. Rather than simply tolerating damaged cells, long-lived bat cells appeared particularly effective at repairing damage or eliminating compromised cells.
Both mechanisms could help reduce the accumulation of mutations over decades of life. That finding provides experimental support for the genomic signal linking longevity with cancer-related pathways rather than relying solely on evolutionary correlations.
What bats could teach human medicine
The study does not mean that bat genes can simply be transferred into humans to extend lifespan or prevent cancer. Many of the adaptations evolved within the unique physiology, metabolism and immune systems of bats, and their effects may depend on complex interactions between multiple genes.
But the work provides a valuable comparative model. Instead of studying ageing, cancer and antiviral immunity as separate biological problems, bats suggest that they may share some of the same underlying molecular pathways.
Understanding how bats maintain effective antiviral defences while avoiding excessive inflammation, controlling DNA damage and suppressing malignant cells could therefore reveal new targets for research into age-related disease and immune regulation.
A different view of viral evolution
The findings also change the way viral exposure can be viewed over evolutionary timescales. Viruses are not simply pathogens attacking their hosts. Over millions of years, they can act as powerful selective forces, reshaping host genomes.
In Myotis, that evolutionary pressure appears to have influenced immune genes, genomic architecture and pathways associated with longevity.
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