Identification of and Characterization of Genes Required for Differentiation of Quiescent and Nonquiescent Cells in Stationary Phase Cultures of Saccharomyces Cerevisiae

Almost all cells on earth are in some type of slow-growing or non-dividing, quiescent state, about which relatively little is known.  Because this state represents a large percentage of any organisms life cycle, it presents a significant opportunity for natural selection.  Saccharomyces cerevisiae (yeast) is an ideal eukaryotic model organism for studying quiescence.  We have found that two cellular fractions differentiate as cultures of yeast enter stationary phase.  These fractions are separable by density and termed non-quiescent (NQ) and quiescent (Q). The NQ fraction is viable but about 50% of cells have high levels of reactive oxygen species (ROS) and lack the ability to reproduce. The other sub-fraction of NQ cells can reproduce, but is genomically unstable.  Quiescent cells are viable, able to reproduce, stress resistant, and genomically stable.   We have used the yeast deletion library (>7000 different mutants) to statistically identify over 400 genes involved in formation of Q cells, including a highly significant representation of genes required for mitochondrial organization and translation.  We have identified over 60 genes that affect formation of NQ cells. We will report on the phenotypic assays of these mutants.  Our goal is to identify the processes and specific levels of regulation required for formation of Q cells, especially those that are also involved in formation of mammalian stem cells.