Abstract
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.
Highlights
Growth condition perturbation or gene function disruption are commonly used strategies to study cellular systems
We show that the signature is similar to the environmental stress response (ESR) gene expression signature, previously described as a cellular response exhibited upon many different environmental perturbations such as nutrient limitations and different types of stress (Brauer et al, 2008; Gasch et al, 2000)
The finding of a slow growth associated expression signature in deletion strains fits with previous reports linking global changes in gene expression to changes in growth rates, in particular growth rate changes caused by various nutrient limitations (Brauer et al, 2008; Keren et al, 2013; Regenberg et al, 2006)
Summary
Growth condition perturbation or gene function disruption are commonly used strategies to study cellular systems. 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. Further analyses show that both the ESR and the expression signature common to slow growing deletion strains result to a large extent from shifts in the proportions of cells in different cell cycle phases. A perturbation can be the targeted disruption of a particular cellular component, for example by gene deletion or through RNA-mediated knockdown. Combinations of these two general types of perturbation are frequently applied.
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