Rare codons are enriched at gene start in many genomes. Genome analysis and experimental testing show that this enrichment evolved to keep the ribosome binding site free from stable mRNA structures, in order to facilitate efficient translation initiation.

Evolutionary selection for robustness of signaling output in the face of stochastic variations in protein expression may explain the organization of bacterial chemotaxis genes.

Mutation rate balances the need to protect genome integrity with the advantage of evolutionary innovations. Microorganisms increase their mutation rate when stressed, perhaps addressing the growing need for evolutionary innovation. Such a strategy, however, is only beneficial under moderate stresses that allow cells to divide and realize their mutagenic potential. In contrast, severe stresses rapidly kill the majority of the population with the exception of a small minority of cells that are in a phenotypically distinct state termed persistence. Although persisters were discovered many decades ago, the stochastic event triggering persistence is poorly understood. We report that spontaneous DNA damage triggers persistence in Saccharomyces cerevisiae by activating the general stress response, providing protection against a range of harsh stress and drug environments. We further show that the persister subpopulation carries an increased load of genetic variants in the form of insertions, deletions or large structural variations, which are unrelated to their stress survival. This coupling of DNA damage to phenotypic persistence may increase genetic diversity specifically in severe stress conditions, where diversity is beneficial but the ability to generate de novo mutations is limited.

Cellular signaling systems show astonishing precision in their response to external stimuli despite strong fluctuations in the molecular components that determine pathway activity. To control the effects of noise on signaling most efficiently, living cells employ compensatory mechanisms that reach from simple negative feedback loops to robustly designed signaling architectures. Here, we report on a novel control mechanism that allows living cells to keep precision in their signaling characteristics – stationary pathway output, response amplitude, and relaxation time – in the presence of strong intracellular perturbations. The concept relies on the surprising fact that for systems showing perfect adaptation an exponential signal amplification at the receptor level suffices to eliminate slowly varying multiplicative noise. To show this mechanism at work in living systems, we quantified the response dynamics of the E. coli chemotaxis network after genetically perturbing the information flux between upstream and downstream signaling components. We give strong evidence that this signaling system results in dynamic invariance of the activated response regulator against multiplicative intracellular noise. We further demonstrate that for environmental conditions, for which precision in chemosensing is crucial, the invariant response behavior results in highest chemotactic efficiency. Our results resolve several puzzling features of the chemotaxis pathway that are widely conserved across prokaryotes but so far could not be attributed any functional role.