The hallmarks of a tradeoff in transcriptomes that balances stress and growth functions

Abstract Fit phenotypes are achieved through optimal transcriptomic allocation. Here, we performed a high-resolution, multi-scale study of the transcriptomic tradeoff between two key fitness phenotypes, stress response (fear) and growth (greed), in Escherichia coli. We introduced twelve RNA polymerase (RNAP) mutations commonly acquired during adaptive laboratory evolution (ALE) and found that single mutations resulted in large shifts in the fear vs. greed tradeoff, likely through destabilizing the rpoB-rpoC interface. RpoS and GAD regulons drive the fear response while ribosomal proteins and the ppGpp regulon underlie greed. Growth rate selection pressure during ALE results in endpoint strains that often have RNAP mutations, with synergistic mutations reflective of particular conditions. A phylogenetic analysis found the tradeoff in numerous bacteria species. The results suggest that the fear vs. greed tradeoff represents a general principle of transcriptome allocation in bacteria where small genetic changes can result in large phenotypic adaptations to growth conditions.