Predicting experimental designs leading to rewiring of transcription program and evolution of anticipatory regulation in E. coli.

Environmental cues in an ecological niche are often temporal in nature. For instance, in temperate climates, temperature is higher in daytime compared to during night. In response to these temporal cues, bacteria have been known to exhibit anticipatory regulation, whereby they trigger response to a yet to appear cue, anticipating its actual arrival in the near future. Such an anticipatory response in known to enhance Darwinian fitness, and hence, is likely an important feature of regulatory networks in microorganisms. However, the conditions under which an anticipatory response evolves as an adaptive response are not known. In this work, we develop a quantitative model to study response of a population to two temporal environmental cues, and predict variables which are likely important for evolution of anticipatory regulatory response. We follow this with experimental evolution of E. coli in alternating environments of a pentose sugar, rhamnose, and an oxidative stress molecule, paraquat for more than 800 generations. We demonstrate that growth in this cyclical environment leads to evolution of anticipatory regulation, whereby, exposure to rhamnose leads to partial induction of the oxidative stress response regulon. As a result, pre-exposure to rhamnose leads to a greater fitness in paraquat environment. Overall, we show that in niches where environmental stimuli have a cyclical nature, anticipatory regulation can evolve as an adaptive strategy, in a time course of a few hundred generations. This contributes to our understanding of how environment shapes the topology of regulatory networks in an organism.