RII Track-4: A Functional Genomics Approach to Explain the Evolution of Large Bodies and Long Life Spans

University Of South Alabama, Mobile AL

Investigators

Abstract

Non-Technical Abstract We use reptiles, specifically giant tortoises, to study the processes behind aging and cancer. Mammals, including humans, have long been used to study these topics, with obvious applications for improving health. However, it is becoming clear that all kinds of animals -not just mammals- have evolved ways of delaying aging and avoiding cancer. Thus, focusing on mammals limits our arsenal for understanding how biology has solved these major physiological challenges. In this project, we will investigate which genes have allowed giant tortoises to mitigate cancer and other biological processes in order to grow so big and live so long. Specifically, we will use cells from long-lived, giant tortoises and their small tortoise relatives to see whether certain genes related to aging and cancer behave differently in these two types of tortoises. This work will not only expand how we look at the importance of animal diversity for meeting challenges in human health, but will also shed light on why we see such amazing diversity in animal life spans and body sizes in nature. The project also has a large outreach component including the development of high school learning modules to teach students cutting-edge technologies in genetics. Technical Abstract Evolutionary theory predicts that natural selection should drive species to grow bigger and live longer because of an improved ability to defend against predators, compete for resources, and invest in offspring. Despite such advantages, there is a major constraint to the evolution of increased body sizes and life spans: the risk of accumulating genotoxic and cytotoxic damage that comes with living longer and having more cells, which can ultimately lead to cancer. Yet, some species have overcome these barriers and have evolved remarkably large body sizes and long life spans, sometimes within a narrow window of evolutionary time. Here, we examine the function of key genes related to longevity and cancer resistance in giant tortoises as compared to their smaller, shorter-lived relatives. These candidate genes have recently been identified from analyzing the newly sequenced genomes of giant Galapagos and Aldabra tortoises. Specifically we will use cell lines from both giant and small tortoises to evaluate the influence of these candidate genes on critical processes including DNA repair, apoptosis, necrosis, and cell viability. Our unique study design, pairing gigantic tortoises with their much smaller relatives, will address a major paradox in biology, and show how evolution has overcome the costs of being large and long-lived. The project also has a large outreach component including the intellectual transfer of advanced cell culture and gene editing technology among universities, the development of high school learning modules, and the development of educational panels and videos for zoos on the biology of cancer and aging. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.