Cell cycle population effects in perturbation studies

Growth condition perturbation or gene function disruption are commonly used strategies to study cellular systems. Although it is widely appreciated that such experiments may involve indirect effects, these frequently remain uncharacterized. Here, analysis of functionally unrelated Saccharyomyces cerevisiae deletion strains reveals a common gene expression signature. One property shared by these strains is slower growth, with increased presence of the signature in more slowly growing strains. The slow growth signature is highly similar to the environmental stress response (ESR), an expression response common to diverse environmental perturbations. Both environmental and genetic perturbations result in growth rate changes. These are accompanied by a change in the distribution of cells over different cell cycle phases. Rather than representing a direct expression response in single cells, both the slow growth signature and ESR mainly reflect a redistribution of cells over different cell cycle phases, primarily characterized by an increase in the G1 population. The findings have implications for any study of perturbation that is accompanied by growth rate changes. Strategies to counter these effects are presented and discussed. Synopsis Genetic, stress, or nutrient perturbation of yeast resulting in slower growth yields a common expression signature, previously known as the environmental stress response. This is largely due to a cell cycle population shift and is relevant to many perturbation-based studies. Yeast deletion strains with slower growth exhibit a common gene expression signature proportional to their degree of slow growth. The slow growth signature is also found in wild-type cells subjected to various environmental perturbations that result in slow growth including the environmental stress response (ESR). The ESR and the genetic perturbation slow growth signature can largely be explained by a redistribution of cells over cell cycle phases. Transformation of slow growth-affected data enriches for finding direct targets of the original perturbation. Genetic, stress or nutrient perturbation of yeast resulting in slower growth yields a common expression signature, previously known as the environmental stress response. This is largely due to a cell cycle population shift and is relevant to many perturbation-based studies.