Genome‐wide transcriptional plasticity underlies cellular adaptation to novel challenge

TLDR

Cells modulate transcription to adapt to environmental and genetic changes, yet it remains unclear how much of this response is evolutionarily selected. The study tests whether adaptive metabolic states can arise from non‑pre‑designed transcriptional reprogramming by exposing yeast to a novel challenge. The authors rewired the essential HIS3 gene into the GAL network and then shifted yeast from galactose to glucose in a chemostat, repressing HIS3 and forcing adaptation over roughly ten generations. Genome‑wide arrays revealed a global reprogramming of over 1,200 genes, many of which were nonreproducible across repeats, indicating that a nonspecific, plastic transcriptional response underlies adaptation to novel challenges.

Abstract

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. 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.