The genomic, environmental, and evolutionary interruptions caused the changes in bacterial growth, which were stringently associated with changes in gene expression. The growth and gene expression changes remained unclear in response to these interruptions that occurred combinative. As a pilot study, whether and how bacterial growth was affected by the individual and dual interruptions of genome reduction, environmental stress, and adaptive evolution were investigated. Growth assay showed that the presence of the environmental stressors, i.e., threonine and chloramphenicol, significantly decreased the growth rate of the wild-type Escherichia coli, whereas not that of the reduced genome. It indicated a canceling effect in bacterial growth due to the dual interruption of the genomic and environmental changes. Experimental evolution of the reduced genome released the canceling effect by improving growth fitness. Intriguingly, the transcriptome architecture maintained a homeostatic chromosomal periodicity regardless of the genomic, environmental, and evolutionary interruptions. Negative epistasis in transcriptome reorganization was commonly observed in response to the dual interruptions, which might contribute to the canceling effect. It was supported by the changes in the numbers of differentially expressed genes (DEGs) and the enriched regulons and functions. Gene network analysis newly constructed 11 gene modules, one out of which was correlated to the growth rate. Enrichment of DEGs in these modules successfully categorized them into three types, i.e., conserved, responsive, and epistatic. Taken together, homeostasis in transcriptome architecture was essential to being alive, and it might be attributed to the negative epistasis in transcriptome reorganization and the functional differentiation in gene modules. The present study directly connected bacterial growth fitness with transcriptome reorganization and provided a global view of how microorganisms responded to genomic, environmental, and evolutionary interruptions for survival from wild nature.

Fitness and mutability are the primary traits of living organisms for adaptation and evolution. However, their quantitative linkage remained largely deficient. Whether there is any general relationship between the two features and how genetic and environmental variables influence them remained unclear and were addressed here. The mutation and growth rates of an assortment of Escherichia coli strain collections, including the wild-type strains and the genetically disturbed strains of either reduced genomes or deletion of the genes involved in the DNA replication fidelity, were evaluated in various media. The contribution of media to the mutation and growth rates was differentiated depending on the types of genetic disturbance. Nevertheless, the negative correlation between the mutation and growth rates was observed across the genotypes and was common in all media. It indicated the comprehensive association of the correlated mutation and growth rates with the genetic and medium variation. Multiple linear regression and support vector machine successfully predicted the mutation and growth rates and the categories of genotypes and media, respectively. Taken together, the study provided a quantitative dataset linking the mutation and growth rates, genotype, and medium and presented a simple and successful example of predicting bacterial growth and mutability by data-driven approaches.