Systems-Level Response to Point Mutations in a Core Metabolic Enzyme Modulates Genotype-Phenotype Relationship

摘要: Linking the molecular effects of mutations to fitness is central understanding evolutionary dynamics. Here, we establish a quantitative relation between global effect on E. coli proteome and bacterial fitness. We created strains with specific destabilizing in chromosomal folA gene encoding dihydrofolate reductase (DHFR) quantified ensuing changes abundances 2,000+ proteins mutant using tandem mass tags subsequent LC-MS/MS. mRNA same were also quantified. The proteomic DHFR are quantitatively linked phenotype: SDs distributions logarithms relative (to WT) protein anticorrelate growth rates. Proteomes hierarchically cluster first by media conditions, within each condition, severity perturbation function. These results highlight importance systems-level layer genotype-phenotype relationship.