We determined the LOH rates in young cells at loci on chromosome IV and chromosome XII simultaneously. By scoring ∼20,000 colonies per time point, we measured an LOH rate of 6.69×10−4 events/cell division at MET15 on chromosome XII and a rate of 1.25×10−4 events/cell division at an intergenic region on chromosome IV (Figure 1A and 1B). The LOH rate at MET15 was significantly higher than the chromosome IV locus (p = 0.0059, Fisher's exact test using contingency tables), suggesting that MET15 LOH rate is affected by proximity to a “hotspot”. As mother cells were aged in liquid culture, a robust and significant increase in LOH rates associated with increasing replicative age was observed at the MET15 locus (Figure 1A). This increase was significant at 45 hours (p<0.0001, Fisher's exact test using contingency tables), a time point where ∼25% of the original mother population retained viability, and continued to increase as the viability of the population declined below 10%. Thus, the increase in LOH rate at MET15 affects cells that have exceeded the median life span potential of the population. In
