Loss of Heterozygosity associated with ubiquitous environments in yeast.

Abstract

The effect of ubiquitous environmental conditions on mutational mechanisms, particularly loss of heterozygosity (LOH) remains poorly understood. Environment induced LOH can rapidly alter the genome and promote disease progression. Using mutation accumulation (MA) lines, we analysed the effect of ubiquitous environmental conditions on mutational mechanisms in a diploid hybrid (S288c/YJM789) baker's yeast strain. These included blue light, low glucose (calorie restriction), oxidative stress (H2O2), high temperature (37°C), ethanol, and salt (NaCl). The frequency of LOH increased significantly in all environments including calorie restriction relative to the control (YPD). Interestingly, the percentage of the genome covered by LOH varied significantly depending on the condition. For example, the LOH tracts seen in calorie restriction conditions were significantly shorter than those observed in blue light exposure that rapidly homozygotized the genome. We also report a unique mutational signature of blue light exposure comprising LOH, small indels, large deletions and transversion mutations (G:C > T:A; G:C > C:G), with the latter likely to result from the photooxidation of guanine bases. Our results suggest ubiquitous environmental conditions cause LOH but result in distinct mutational signatures due to the type of damage induced and the pathways used to repair them.