title: Genome-wide transcriptional plasticity underlies cellular adaptation to novel challenge.
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.
authors: Department of Chemical Engineering, Technion-Israel Institute of Technology, Haifa, Israel.
authors: Shay
authors: S
authors: Stern
authors: Tali
authors: T
authors: Dror
authors: Elad
authors: E
authors: Stolovicki
authors: Naama
authors: N
authors: Brenner
authors: Erez
authors: E
authors: Braun
mesh_terms: D000220:Adaptation, Biological; D000222:Adaptation, Physiological; D016000:Cluster Analysis; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D016681:Genome, Fungal; D005947:Glucose / Q000378:metabolism; D008954:Models, Biological; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D005947:Glucose