Bibi, N; (2013) Impact of ploidy and cell size on genome expression in fission yeast. Doctoral thesis (PhD), UCL (University College London).

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Abstract

Cells are classified based on their ploidy into haploids, containing a single chromosome set, diploids, containing two chromosome sets, polyploids, containing more than two chromosome sets, and aneuploids, containing abnormal chromosome numbers. Polyploidy is typically accompanied by increased cell size. Polyploid cells are found in most tumors and exhibit chromosomal instability that leads to aneuploidy. The effects of aberrant ploidy on genome regulation and on cell size are not well understood. I used fission yeast as a model to analyse impacts of altered ploidy and cell size on gene expression. Using aneuploids that are disomic or trisomic for a portion of chromosome III, I find that total mRNA levels scale with DNA copy numbers. Aneuploidy also affects the transcription of some genes present in monosomic areas, possibly reflecting associated regulatory genes in disomic or trisomic areas. I also analysed the effect of polyploidy on genome expression by constructing diploid and tetraploid strains. Diploids were stable with normal cell shape, while tetraploids showed irregular morphologies and often lost chromosomes. Increased ploidy resulted in increased cell size, and also in a linear increase in cellular RNA levels. Using spike-in controls and normalization, we showed that increased transcription in polyploids does not affect ratios between total RNA and mRNA. Cells kept a tight control on genome-wide transcription which generally scaled with the copy numbers of genes, a few genes were differentially regulated as a function of polyploidy and/or cell size. These genes were present in multiple copies close to telomeres and may function at the cell surface. They were also differentially regulated in haploid cell-size mutants, indicating a role of cell size, rather than ploidy, in controlling these genes. Intriguingly, deletion and overexpression of these genes in turn resulted in a significant decrease or increase in cell size, respectively, raising the possibility that the genes are involved in size control.

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