Determining the contribution of gene duplication to the resolution of healthy aging in long-lived species

Abstract Project Title: Determining the contribution of gene duplication to the evolution of healthy aging in large, long-lived species Project Summary: A major constraint on the evolution of large body sizes and long lifespans in animals is an increased risk of developing cancer. If all cells have a similar risk of malignant transformation and equivalent cancer suppression mechanisms, organism with many cells should have a higher risk of developing cancer than organisms with fewer cells. Similarly, organisms with long lifespans have more time to accumulate cancer-causing mutations than organisms with shorter lifespans and therefore should be at an increased risk of developing cancer, a risk that is compounded in large-bodied, long-lived organisms. There are no correlations, however, between body size and cancer risk or lifespan and cancer risk across species, this lack of correlation is often referred to as `Peto's Paradox'. The project proposes to use a combination of comparative genomics to identify genes that may be associated with the evolution of large bodies and long-lifespans in elephants, Bowhead whales, and Myotis bats. Candidate genes will be functionally characterized in experimental studies to identify those that are causally related to the cancer biology and ageing. These studies will identify the mechanisms by which elephants, Bowhead whales, and Myotis bats evolved enhanced cancer resistance and provide new insights into the mechanisms of evolution and the biology of cancer.