Extraordinary variation in radiation tolerance: Mechanisms and evolution

Ionizing radiation is a potent environmental mutagen, producing damaged bases and single and double-stranded DNA breaks. Acute high-dose radiation exposure is therefore toxic, causing cellular and organismal mortality, while lower doses can give rise to high mutation rates and cancer. Radiation sensitivity furthermore varies dramatically between organisms and cell types, with certain organisms exhibiting extreme tolerance to ionizing radiation. It is puzzling however, how such radiotolerance evolved in nature, as toxic radiation doses are not observed outside of medical and nuclear settings. In this review, we explore the mechanisms and evolution of extraordinary radiotolerance in metazoans. We contrast two extensively studied genetic models, mammals and Caenorhabditis elegans, as well as two lineages known to tolerate extreme radiation when compared to closely related species: naked mole rats and tardigrades. We describe similar strategies employed by these disparate lineages to protect DNA, repair DNA, and attenuate cellular responses following radiation exposure. We further discuss how these mechanisms may have evolved in response to other extreme conditions tolerated by each species in their natural environment, giving rise to radiotolerance as a correlated response.