The Role of Gene Duplication in Mediating Peto's Paradox in Afrotheria and Chiroptera

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.