Cells adjust their transcriptional state to accommodate
environmental and genetic perturbations. An open question is to what extent
transcriptional response to perturbations has been specifically selected along
evolution. To test the possibility that transcriptional reprogramming does not
need to be ‘pre-designed’ to lead to an adaptive metabolic state on
physiological timescales, we confronted yeast cells with a novel challenge they
had not previously encountered along evolution. We rewired the genome by recruiting
an essential gene, HIS3, from the histidine biosynthesis pathway to a foreign
regulatory system, the GAL network responsible for galactose utilization.
Switching medium to glucose in a chemostat caused repression of the essential
gene and presented the cells with a severe challenge to which they adapted over
approximately 10 generations. Using genome-wide expression arrays, we show here
that a global transcriptional reprogramming (>1200 genes) underlies the
adaptation. A large fraction of the responding genes is nonreproducible in
repeated experiments. These results show that a nonspecific transcriptional
response reflecting the natural plasticity of the regulatory network supports
adaptation of cells to novel challenges.
