A Full-Locus Duplication of TP53 Enhances the Stress Response of the Little Brown Bat, *Myotis lucifugus*


While there exists a clear correlation between size, lifespan, and cancer risk between individuals of a species, this correlation does not hold when comparing across species, a phenomenon known as Peto’s Paradox. Bats represent an ideal clade to study this paradox, as the large number of extant members - combined with the recent divergence time of the order - preserves a detailed record of the various genetic changes underlying their diversity in body size and lifespan. Previous work performed by our group revealed that the long-lived bat, Myotis lucifugus, has 8 copies of TP53, a central regulator of the DNA damage response present in all living organisms. Two of these copies, the canonical locus plus a second full-locus duplication, are unique to M. lucifugus, and show high levels of transcription in publically-available RNA-seq studies. We show that these two loci are expressed in primary cell lines of different M. lucifugus individuals, and contribute to an enhanced DNA damage response in M. lucifugus relative to 4 other closely related bat species (M. evotis, M. thysanodes, M. yumanensis, and E. fuscus). These results contribute to our understanding of how pre-existing tumor suppressor mechanisms have been enhanced through gene duplication to resolve Peto’s Paradox in large, long-lived organisms.”