Chromosome loss rate in cells of different ploidy can be explained by spindle self-organization

Abstract

The mitotic spindle segregates chromosomes and minimizes chromosome loss for the specific number of chromosomes present in an organism. In Saccharomyces cerevisiae, for example, haploid and diploid cells are part of the sexual life cycle and have a thousand times lower rate of chromosome loss than tetraploid cells. Currently it is unclear what constrains the number of chromosomes that can be segregated with high fidelity in an organism. Here we developed a mathematical model to study if different rates of chromosome loss in cells with different ploidy can arise from changes in (1) spindle dynamics and (2) a maximum duration of mitotic arrest, after which cells enter anaphase. Our model reveals how small increases in spindle assembly time can result in exponential differences in rate of chromosomes loss between cells of increasing ploidy and predicts the maximum duration of mitotic arrest.