Stochastic variation in single cells

About this book

Protein production involves a series of stochastic chemical steps. A consequence of this is that the copy number of any given protein varies substantially from cell-to-cell even within isogenic populations [1-13]. In this work, we investigate several possible contributing sources to this cellular individuality, including the roles that chromosomal position, gene copy-number, noisy upstream regulators, and weak expression levels all play. We discovered that the fluctuations we observed were not due to the low number of the molecules expressed from a gene per se , but instead originated in the random, rare events of gene activation. The frequency of these events and the correlation between stochastic expressions of genes within a single cell depend on the positioning of the genes along the chromosomes. Finally, we showed that natural transcriptional regulators subject to such random expression can propagate their noise to their target genes. Next we investigated the role stochasticity plays in epigenetic or non-Mendelian inheritance. To accomplish this, we tracked families of the yeast Saccharomyces cerevisiae as they switched between two semi-stable epigenetic states. We found that long after two cells divided they continued to switch in a synchronized manner, despite our observation that individual cells switch in an exponentially distributed manner. By comparing these results to a model Poisson process, we show that the time-evolution of an epigenetic state depends initially on inherited factors, with stochastic processes requiring several generations to decorrelate closely related cells.