A unified model of aneuploid karyotype dynamics.

Aneuploidies-whole-chromosome copy number imbalances arising from nondisjunction-underlie numerous congenital and somatic disorders, but unlike many other disease-causing variants, they can readily revert back to euploidy through subsequent errors of the same type. The extent to which this inherent plasticity impacts the stability and persistence of aneuploid karyotypes in populations remains poorly understood, a gap in knowledge that continues to limit our understanding of aneuploidy-driven disease incidence, penetrance, and progression. To assess how reversion shapes aneuploid population dynamics, we developed a budding yeast system to systematically measure the rates at which aneuploidies arise and revert, and quantify the relative fitness differences between these karyotypic states. We integrated these data into a computational framework encompassing the broad physiological range of aneuploid karyotype dynamics captured in our experiments. The resulting models reveal that canonical reversion (