Bats' virus defenses and their long, cancer-free lives may be the same genes doing double duty

The mechanism the authors lean on is pleiotropy, one gene holding down more than one job. If the genes that adapted under viral pressure are the same genes sitting in longevity and cancer pathways ^[9], the bat's three famous tricks are not separate systems but one system read three ways. That is the move that matters for anyone hunting drug targets: a locus an immunologist flagged for antiviral work becomes, on this account, a candidate an oncologist or a longevity researcher would want too.

The route the paper emphasizes is copy-number variation rather than point mutation. Co-lead author Elise Lauterbur of the University of Vermont argues that coding changes usually break a gene rather than repurpose it, while duplicating a gene lets one copy keep its old function and another diversify ^[12]. The worked example is EIF2AK2, also called PKR, a key immune factor the team found duplicated in Myotis-specific ways and carrying ancient copy-number polymorphisms shared across species ^[11].

The sharpest contrast with humans is in which viruses did the shaping. Across the genome the bats show positive selection for proteins that interact with DNA viruses and raised copy-number variation for those interacting with RNA viruses ^[3], a pattern the authors say differs from every other mammal they examined ^[4]. Humans run the other way, with selection concentrated on RNA-virus proteins such as those engaging SARS-CoV-2 and influenza, while bats lean toward DNA viruses like hepatitis B and herpesviruses ^[5]. The authors read that mismatch as one reason a pathogen crossing between the species can find both poorly prepared ^[6]. On the aging side, the repeated evolution of long life across Myotis tracks with positive selection in cancer pathways ^[7], and primary cells from the long-lived little brown bat showed a distinctive response to DNA damage ^[8].

There is real spread to work with. Within the genus lifespan varies sixfold, from Myotis brandtii at 42 years to Myotis nigricans at 7, in lineages that split only about 10.6 million years ago ^[13]. That closeness is the useful part, because it narrows the set of genetic differences that could explain so large a gap.

The evidence, published in Nature ^[1], rests on eight near-complete genome assemblies that place an average of 98.6% of nucleotides on 22 to 23 chromosomal scaffolds ^[16], built from wing skin punches rather than dissected organs, a sampling method co-lead author Manny Vazquez of Penn State designed so the animals live ^[14]. That matters most for the little brown bat, North America's longest-lived bat and the species hit hardest by white-nose syndrome ^[15]. The correlations are strong and the cell work is suggestive, but the paper stops at linkage.