Fluctuating environments that consist of regular cycles of co-occurring stress are a common challenge faced by cellular populations. For a population to thrive in constantly changing conditions, an ability to coordinate a rapid cellular response is essential. Here, we identify a mutation conferring an arginine-to-histidine (Arg to His) substitution in the transcription terminator Rho. The R109H mutation frequently arose in populations experimentally evolved under repeated long-term starvation conditions, during which the accumulation of metabolic waste followed by transfer into fresh media results in drastic environmental pH fluctuations associated with feast and famine. Metagenomic sequencing revealed that populations containing the mutation also possess putative loss-of-function mutations in , which encodes a recently characterized transcription factor associated with pH homeostasis. Genetic reconstructions of these mutations show that the allele confers plasticity via an alkaline-induced reduction of Rho function that, when found in tandem with a Δ allele, leads to intracellular alkalization and genetic assimilation of Rho mutant function. We further identify Arg to His substitutions at analogous sites in alleles from species that regularly experience neutral to alkaline pH fluctuations in their environments. Our results suggest that Arg to His substitutions in Rho may serve to rapidly coordinate complex physiological responses through pH sensing and shed light on how cellular populations use environmental cues to coordinate rapid responses to complex, fluctuating environments.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11441560PMC
http://dx.doi.org/10.1073/pnas.2405546121DOI Listing

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