Information Processing In Single Yeast Cells: Homogeneous Signal Transduction Result In Heterogeneous Gene Expression

Abstract

How cells sense their environment using signal transduction pathways and respond to environmental changes by regulating gene expression is a key problem in systems biology. The mitogen-activated protein kinase (MAPK) pathways, which are evolutionarily conserved from yeast to mammals, provide an excellent model to study how signal transduction is coupled to gene expression. Our research focus on the high-osmolarity glycerol (HOG) MAPK pathway in single, Saccharomyces cerevisiae yeast cells. During the last few decades, the components and regulatory network of this pathway have been elucidated via genetic and biochemical assays performed on large populations of yeast cells. However, surprisingly little is known about the detailed coupling dynamics of signal transduction and gene expression in individual cells. After osmotic shock, homogeneous Hog1 kinase dynamics were measured in all cells. In the subsequent gene expression of STL1, a gene that encodes for a glycerol proton symporter of the plasma membrane, we observed that one subpopulation of cells exhibits no gene expression at all (OFF-population), whereas another subpopulation of cells show gene expression over a wide range of expression levels (ON-population). Further, the ratio of the two subpopulations of cells remained constant despite changes in osmolyte concentration from 0.3 M to 0.6 M NaCl. To identify the origin of the bi-modality in gene expression, we over expressed specific transcription factors that regulate STL1 - gene expression. After over expression of one specific transcription factor, we observed a mono modal gene expression distribution for STL1. Furthermore, single cell time-lapse experiments, indicate that switching between gene expression levels after subsequent osmotic shocks was random and uncorrelated. These results indicate, that at least one transcription factor is responsible for the bi-modality and stochasticity in gene expression.