Genome‐wide transcriptional plasticity underlies cellular adaptation to novel challenge

Abstract

By recruiting the essential HIS3 gene to the GAL regulatory system and switching to a repressing glucose medium, we confronted yeast cells with a novel challenge they had not encountered before along their history in evolution.Adaptation to this challenge involved a global transcriptional response of a sizeable fraction of the genome, which relaxed on the time scale of the population adaptation, of order of 10 generations.For a large fraction of the responding genes there is no simple biological interpretation, connecting them to the specific cellular demands imposed by the novel challenge.Strikingly, repeating the experiment did not reproduce similar transcription patterns neither in the transient phase nor in the adapted state in glucose.These results suggest that physiological selection operates on the new metabolic configurations generated by the non-specific large scale transcriptional response to eventually stabilize an adaptive state.

Inherited adaptation of genome‐rewired cells in response to a challenging environment

“…The process that leads to cell arrest in our experiments is presumably different from the one observed during starvation since it is imposed only on some of the cells and because it facilitates the generation of an adapted state in others. This observation might be supported by our previous work showing that along phase I there has been a genomewide arbitrary transcriptional response involving a large fraction of the genome and having a very small overlap with known stress responses (Stern et al, 2007). Such a dramatic transcriptional response might significantly affect the physiology in ways that on the one hand will lead to cell arrest but on the other will open up new opportunities for adaptation.…”

“…In previous studies, the growth dynamics of the population upon exposure to Glu-his was studied in a chemostat (Novick and Szilard, 1950) in which large populations of rewired cells were grown in Gal-his and switched to Glu-his medium under controlled and otherwise stable environmental conditions. Our chemostat setup allowed us to monitor online the cell density [optical density (OD)] and automatically sample the population at a high temporal resolution for further analyses of the cells [see examples in Stolovicki et al (2006) and Stern et al (2007)]. In this study, repeated chemostat experiments were carried out under identical conditions and the reproducible patterns of the population growth dynamics pointed out to a few robust features (Fig.…”

“…The cells had not exercised regulation of HIS3 by carbon sources availability along their history, so a substantial adaptive response was required for them to survive in a medium lacking histidine. Recently, we have shown that a cell population carrying this GAL-HIS3 rewired genome can rapidly adapt to grow competitively in histidine-lacking glucose medium despite the strong repression of the GAL system and HIS3 (Stolovicki et al, 2006;Stern et al, 2007). Once established, the adaptation have been propagated stably for hundreds of generations (Stolovicki et al, 2006).…”

Dispensability of Escherichia coli ’s latent pathways

“…This scenario cannot be rejected by existing experimental results (30) and is appealing as it allows for an indirect, long-term benefit of temporary reaction activation even if, as predicted here, this activation inhibits growth in the short term. Although whole-cell regulation remains largely unexplained, there are known mechanisms that could subsequently lead to optimal growth (43,44).…”

The enemy within: An epigenetic role of retrotransposons in cancer initiation

“…The most dramatic case of transcriptional reprogramming following a stress involves a genetically engineered form of starvation for histidine in yeast [30], which transcriptionally reprograms more than 1,000 genes (although the gene sets are different in different cells) [31]; the involvement of RTNs in this system has not yet been established, however.…”