Indirect and suboptimal control of gene expression is widespread in bacteria

Gene regulation in bacteria is usually described as an adaptive response to an environmental change so that genes are expressed when they are required. We instead propose that most genes are under indirect control: their expression responds to signal(s) that are not directly related to the genes’ function. Indirect control should perform poorly in artificial conditions, and we show that gene regulation is often maladaptive in the laboratory. In Shewanella oneidensis MR‐1, 24% of genes are detrimental to fitness in some conditions, and detrimental genes tend to be highly expressed instead of being repressed when not needed. In diverse bacteria, there is little correlation between when genes are important for optimal growth or fitness and when those genes are upregulated. Two common types of indirect control are constitutive expression and regulation by growth rate; these occur for genes with diverse functions and often seem to be suboptimal. Because genes that have closely related functions can have dissimilar expression patterns, regulation may be suboptimal in the wild as well as in the laboratory. This study shows that, in bacteria grown in the laboratory, there is little correlation between when genes are important for fitness and when they are more highly expressed. Most genes thus appear to be regulated by signals that are not related to their function. Synopsis This study shows that, in bacteria grown in the laboratory, there is little correlation between when genes are important for fitness and when they are more highly expressed. Most genes thus appear to be regulated by signals that are not related to their function. Many bacterial genes are expressed when they are detrimental to fitness. Most genes are not upregulated when they are important for fitness. Even biosynthetic genes are often not downregulated when they are not needed (except in E. coli ). Genes with closely related functions often have different expression patterns.