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Cancer is the result of the accumulation of mutations in the DNA of somatic tissue during the lifetime of an organism. Therefore, animals that live longer and/or have a larger number of cells should have a higher incidence of cancer. However there appears not to be no clear correlation between the longevity or body-size of a species and its rates of cancer incidence This lack of an expected correlation is known as ‘Peto’s paradox’. One potential explanation of this paradox is that as species increase in size or longevity there is selection for mechanisms to decrease cancer risk. One potential mechanism for this Is reducing the somatic mutation rate. However, we currently know almost nothing about the somatic mutation rate in non-human species. To address this, we plan to compare the somatic mutation rate in a range of species. In particular, mice and naked-mole rats have a similar body size yet differ drastically in their longevity, with laboratory mice having a maximum life-span of a few years while naked-mole rats can live >32 years. By quantifying the somatic mutation rate of these species using whole-genome sequence data from monoclonal colonies derived from blood stem cells and laser-capture microdissected individual colonic crypts we will be able to compare the somatic mutation rate across these species. We will also compare the mutational signatures of these species, to learn more about the variation in the mutational processes that underlie somatic mutation across species. These results are expected to further our understanding of the evolution of the somatic mutation rate across species and may have implications for our understanding of cancer. |