Cell integrity limits ploidy in budding yeast

Evidence suggests that increases in ploidy have occurred frequently in the evolutionary history of organisms and can serve adaptive functions to specialized somatic cells in multicellular organisms. However, the sudden multiplication of all chromosome content may present physiological challenges to the cells in which it occurs. Experimental studies have associated increases in ploidy with reduced cell survival and proliferation. To understand the physiological challenges that suddenly increased chromosome content imposes on cells, we used S. cerevisiae to ask how much chromosomal DNA cells may contain and what determines this limit. We generated polyploid cells using 2 distinct methods causing cells to undergo endoreplication and identified the maximum ploidy of these cells, 32-64C. We found that physical determinants that alleviate or exacerbate cell surface stress increase and decrease the limit to ploidy, respectively. We also used these cells to investigate gene expression changes associated with increased ploidy and identified the repression of genes involved in ergosterol biosynthesis. We propose that ploidy is inherently limited by the impacts of growth in size, which accompany whole-genome duplication, to cell surface integrity.