Tuesday, April 24, 2007

Cellular adaptation to unforeseeable events

How do cells react to changes in external conditions ? It has been noted before than in many cases the immediate transcriptional response includes unspecific changes in gene expression for a large group of genes (Gash et al, 2000). Fong and colleagues have shown that in E. coli, 20 to 40 days after the initial changes, most of the genes return to expression levels prior to the modifications of the environment. The differentially expressed genes at this stage are situation specific but not necessarily always the same. In this same paper, the gene expression changes were followed for different independent populations evolving under the same changes in conditions. Out of ~1100 gene expression changes (on average) that were possibly adaptive to the new conditions, only 70 were common to all 7 parallel populations.

A new studied published in MSB, adds more information to these interesting findings. In this study the authors tried to challenge S. cerevisiae with a perturbation that these cells should not have seen during their evolutionary history. They used a his3 deletion strain with a plasmid having HIS3 under the GAL1 promoter. In these cells the essential HIS3 gene should be efficiently turned off in a glucose medium. They then tracked the gene expression changes over time when the medium was changed from galactose to glucose. The cells adapted to these conditions within around 10-20 generations. Again the initial gene expression changes involved a large number of genes (~1000-1600 genes> 2 fold change) with most of them (65%-70% ) returning to their original expression levels in 10-20 generations. Again, different populations had different genes differentially expressed in response to the transition from gal to glu.

There is a detailed analysis in the paper regarding the functional classes of the genes but for me these general trends were by themselves very interesting. How does the cell cope with unforeseeable events ?

Maybe there is a general mechanism that senses discrepancies between metabolic requirements and the current cellular state and, in the absence of a programed response, drives an almost chaotic search for plausible solutions ? If there is such a sensing mechanism it could provide the necessary feedback for the selection of cellular states at a physiological time scale. In a environment were frequent unpredictable changes occur such a system could possibly be selected for.

For further reading have a look at the news and views by Eugene Koonin