Bats are extraordinarily long-lived relative to other mammals; among them, *Myotis lucifugus* is one of the longest-lived bats. While *M. lucifugus* and other closely-related species of bats have been the focus of research for a long time, there have been no reported cases of cancer in the literature - despite their long lifespan - suggesting that they have a low lifetime risk of cancer. In this bat, we find that there is a duplication of the TP53-WRAP53 locus, which is the only such known duplication among sequenced species. The two loci show active transcription both *in vivo* and *in vitro* in primary fibroblasts, suggesting that they are both functional. The responses to DNA damage response in *M. lucifugus* relative to its closest relatives is reminiscient of the effects of a TP53-WRAP53 duplication in transgenic mouse models, suggesting that this duplication may play an important role in mediating the cancer resistance of *M. lucifugus*.
Based on emperical studies of humans, mice, and various other species, an individual's cancer risk is directly proportional to their cell count (body size) and lifespan. This leads to a theoretical prediction that large and/or long-lived species would possess a higher predisposition to cancer compared to smaller, shorter-lived species; compounding this risk is the fact that body size and lifespan are strongly correlated. However, in a phenomenon known as Peto's Paradox, cancer risk between species does not correlate with either their body sizes or lifespans. This implies that enhanced cancer resistance mechanisms must co-evolve with increases in body size and lifespan; however, there are many ways this can come about. Rather than reinventing the wheel, species can carry an increased load of cancer risk by increasing the number of wheels they have. My thesis focuses on the role tumor suppressor gene duplications play in Peto's Paradox: Chapter 1 explores whether or not tumor suppressor genes are especially enriched among duplicated genes in large, long lived species, while Chapters 2 and 3 functionally characterize two such duplications. Overall, my work here highlights the vital role that tumor suppressor gene duplicates play in lowering the cancer risk of large, long-lived species, while also highlighting new questions for future work, especially regarding antagonistic pleitropy and growth-suppression paradoxes with these duplicates.
My acceptance talk on behalf of UC SACNAS for the 2019 Chapter of the Year award.
A talk I gave for the Student Honors section for the 2019 NASBR meeting, on the TP53-WRAP53 duplication in the Little Brown Bat, *Myotis lucifugus*
A talk I gave at the 2019 Biology of Aging GRC on the TP53-WRAP53 duplication in the Little Brown Bat, *Myotis lucifugus*