Abstract

Organisms accumulate mutations in somatic cells throughout their lifetime. This process can lead to cancer and may contribute to aging. Advances in genome sequencing have enabled us to study how mutations accumulate in human tissues with age. However, we know almost nothing about how mutations accumulate in other species. A better understanding of these processes in other species could help resolve long-standing biological mysteries. For example, species with larger body-sizes and longer lifespans should have a higher incidence of cancer, yet no such correlation exists. This is known as ‘Peto’s Paradox’. Additionally, species age at remarkably different rates yet the underlying mechanisms behind these differences remain unclear. Changes in the rate at which species acquire mutations as they age could contribute to both processes. To address these questions, we combine laser-capture microscopy of colonic crypts with whole genome sequencing to quantity and compare mutation rates across mammalian species. Analysing these data in combination with lifespan data records provides insights into the evolution of the mutation rate across species with implications for our understanding of cancer and ageing across species.