Growth arrest and chromosome instability in aneuploid yeast

Aneuploid generation and stability are biologically important. In the present study, we investigated fission yeast aneuploids, focusing on the process through which aneuploidy is resolved into stable euploidy. The viability and growth patterns of aneuploid spores were greatly influenced by culture conditions, including nutrition and temperature. Germ tube formation and DNA synthesis in a major portion of aneuploids were greatly delayed or arrested. Observation of individual spores and their growth profiles revealed that a certain type(s) of aneuploid resolved its aneuploidy into normal euploids through anomalous cell divisions, which in many cases produced dead cells. Another type of aneuploid, disomy of chromosome 3, the only maintainable aneuploid between n and 2n, showed a peculiar cell division arrest phenotype under a certain growth condition. Microcolonies that formed from this type of aneuploid often contained a population of cells that became incompetent for cell division. This cell division arrest was not due to a nutritional limitation. During this peculiar process of colony formation, stable haploids or diploids were frequently produced. All other types of aneuploids are usually inviable, at least under our experimental conditions. To examine the aneuploid issue more systematically, we constructed a system to select for disomy of chromosome 1 or 2 using intragenic complementation of ade6-M210 and -M216 alleles. This genetic selection system revealed that fission yeast aneuploids can be stabilized through structural chromosome changes, including partial duplication and circular mini-chromosomes.