Nature reports eight near-complete Myotis genomes and laboratory-grown cells for comparing immunity and longevity
Nature reports eight near-complete Myotis genomes and laboratory-grown cells for comparing immunity and longevity
On August 26, Nature published a study of eight closely related bat species in the genus Myotis. The authors assembled near-complete genomes and established primary cell lines from skin samples, providing cells that can be studied in the laboratory. Differences in lifespan among closely related species make it possible to test how antiviral defenses and responses to DNA damage are associated with aging.
The genus Myotis contains more than 139 described species across six continents. Lifespan varies almost sixfold among closely related species: M. brandtii lives for up to 42 years, whereas M. nigricans lives for about seven years. Closely related species have fewer differences unrelated to longevity, so this lifespan gap helps narrow the search to specific gene variants and cellular responses.
The authors assembled the chromosome copies inherited from each parent separately and established primary cell lines from skin. This approach allows large DNA rearrangements and differences in gene copy number to be compared with cellular responses to DNA damage and viral infection.
Genes that interact with viruses showed two distinct evolutionary patterns. Proteins associated with DNA viruses more often showed evidence of natural selection, whereas genes associated exclusively with RNA viruses showed greater variation in copy number. The genomes identify several specific changes that can now be tested individually.
One such test examined DNA damage. In M. lucifugus, one of the longest-lived species, evidence of natural selection occurred more often in genes associated with cancer and the repair of DNA double-strand breaks, which affect both strands of the molecule. The researchers induced these breaks in primary skin cells and compared the response with cells from four other bat species. At high doses of the damaging agent, M. lucifugus cells initiated apoptosis, or programmed cell death, more often and had lower survival.
The history of the PKR gene shows why genomes of this accuracy are useful. PKR becomes active when a cell detects viral double-stranded RNA. It slows protein synthesis and limits viral replication. The authors distinguished genomic regions containing one, two, or three copies of PKR, then introduced these copies into human cells in which the native PKR gene had been disabled. When two copies functioned together, they produced an intermediate reduction in protein synthesis and limited the replication of two laboratory RNA viruses no more strongly than either copy alone. These experiments connected differences in copy number with a measurable protein function.
The authors propose that selection associated with innate antiviral defense may also have affected the cell cycle, the response to DNA damage, and traits related to aging. The genomes and cell lines make it possible to test this proposed link among closely related species and to distinguish the effects of specific variants and cellular responses from the broader similarities shared by bats.