Aneuploidy of Specific Chromosomes is Beneficial to Cells Lacking Spindle Checkpoint Protein Bub3

Aneuploidy typically poses challenges for cell survival and growth. However, recent studies have identified exceptions where aneuploidy is beneficial for cells with mutations in certain regulatory genes. Our research reveals that cells lacking the spindle checkpoint gene BUB3 exhibit aneuploidy of select chromosomes. While the spindle checkpoint is not essential in budding yeast, the loss of BUB3 and BUB1 increases the probability of chromosome missegregation compared to wildtype cells. Contrary to the prevailing assumption that the aneuploid cells would be outcompeted due to growth defects, our findings demonstrate that bub3Δ cells consistently maintained aneuploidy of specific chromosomes over many generations. We investigated whether the persistence of these additional chromosomes in bub3Δ cells resulted from the beneficial elevated expression of certain genes, or mere tolerance. We identified several genes involved in chromosome segregation and cell cycle regulation that confer an advantage to Bub3-depleted cells. Overall, our results suggest that the gain of specific genes through aneuploidy may provide a survival advantage to strains with poor chromosome segregation fidelity.