Shining light on hibernator genomes: using radiation to reveal DNA damage and repair dynamics in Arctic ground squirrels

Abstract

Mammalian hibernation is characterized by dynamic changes in metabolism and body temperature; it may be sustained for up to nine months in some species. The majority of hibernation is spent in torpor, a dormant state, which is regularly interrupted by brief periods of activity referred to as interbout arousal. Upon arousal thermogenesis begins in vascularized fat and ends with whole-body shivering until the animal reaches a body temperature around 36-37 °C. Interbout arousal is usually less than a day long and is commonly thought to be necessary for maintenance and repair of tissues, in addition to the cycling and replenishment of metabolites. While physiologically extreme, torpor-arousal cycles do not drastically impact the health of hibernators. Rather, hibernators are recognized for their longevity and resistance to a variety of stresses, such as ischemia/reperfusion and the brain damage that typically follows. It remains unknown how the process of hibernation challenges genome stability and the basic molecular mechanisms of DNA repair. Therefore, this thesis begins with a review on current knowledge of genome maintenance in the context of mammalian hibernation, distinguishing it from other similar and often correlated conditions like hypothermia. Then, we present the first cellular and molecular study to be conducted on DNA damage and repair dynamics in a hibernator using the Alaskan arctic ground squirrel. Our results indicate that hibernators can avoid genome instability during torpor-arousal cycles through status-specific combinations of strategies for preventing DNA damage and efficient DNA repair, paired with anti-apoptotic environments. The unique suite of adaptations necessary to endure torpor-arousal cycles may help explain the longevity and radio-resistance that are often observed in hibernating species.