Cellular Adaptation Through Fitness-Directed Transcriptional Tuning

Cells adapt to changes in their environment through transcriptional responses that are hard-coded in their regulatory networks. Such dedicated pathways, however, may be inadequate for adaptation to novel or extreme environments. We propose the existence of a fitness optimization mechanism that tunes the global transcriptional output of a genome to match arbitrary external conditions in the absence of dedicated gene-regulatory networks. We provide evidence for the proposed tuning mechanism in the adaptation of Saccharomyces cerevisiae to laboratory-engineered environments that are foreign to its native gene-regulatory network. We show that transcriptional tuning operates locally at individual gene promoters and its efficacy is modulated by genetic perturbations to chromatin modification machinery.