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Bacterial growth is closely tied to nutrient availability, with cells proliferating exponentially under favorable conditions and entering a stationary phase when resources become scarce. This transition is mediated by a regulatory mechanism known as the stringent response, which allows bacteria to adapt to nutrient deprivation by modulating gene expression and metabolic activity.During nutrient scarcity, intracellular amino acid levels decline. It results in the accumulation of uncharged tRNAs...
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Gene expression in prokaryotes is governed by constitutive and regulated systems, allowing cells to balance the production of essential proteins with adaptive responses to environmental changes.Constitutive Gene ExpressionConstitutive, or housekeeping, genes are continuously expressed as they encode proteins vital for fundamental cellular processes. These include enzymes for glycolysis, ribosomal components for protein synthesis, and proteins involved in DNA replication. Their constant...
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Bacterial protein maturation is a tightly regulated process that ensures newly synthesized polypeptides achieve correct functional conformations. This maturation involves a series of modifications, folding events, and quality control steps, often assisted by specialized chaperone proteins.N-Terminal ModificationsThe maturation of bacterial polypeptides begins cotranslationally as the polypeptide exits the ribosome. The first amino acid, N-formylmethionine (fMet), is typically modified at the...
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Crenarchaeota, a prominent phylum of Archaea, is remarkable for its ability to thrive in extreme environments characterized by high temperatures and acidity. These microorganisms inhabit sulfuric hot springs, volcanic systems, and submarine hydrothermal vents, where temperatures often exceed 100°C. The unique adaptations of Crenarchaeota not only allow survival under such extreme conditions but also provide insights into the mechanisms of life in primordial Earth-like...
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The DNA replication, transcription, and translation processes are intricately coupled in bacteria, allowing efficient gene expression and rapid protein synthesis. While this physical and functional coordination is advantageous, it introduces challenges that bacteria overcome through specific regulatory mechanisms.Coupling of Replication, Transcription, and TranslationThe coupling of replication, transcription, and translation is a hallmark of bacterial gene expression. As the replisome unwinds...
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Adaptive genetics reveals constraints on protein structure/function by evolving E. coli under constant nutrient

Katja Schwartz1, Margie Kinnersley2, Charles Ross Lindsey3

  • 1Department of Genetics, Stanford University School of Medicine, Stanford, CA, 94305-5120, USA.

BMC Biology
|August 19, 2025
PubMed
Summary

Adaptive genetics reveals key genes and mutation sites driving bacterial adaptation under nutrient limitation. This method identifies specific genetic changes conferring a selective advantage in evolving E. coli populations.

Keywords:
E. coliAdaptive geneticsExperimental evolutionFunctional genomicsMetabolic networksParallelismWhole genome sequencing

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Area of Science:

  • Microbiology
  • Evolutionary Biology
  • Genomics

Background:

  • Microbial evolution under laboratory selection generates genetic diversity through mutations and competition.
  • Whole-genome sequencing enables identification of adaptive mutations and mapping of gene structure-function relationships.
  • Adaptive genetics leverages these capabilities to study adaptation in evolving microbial populations.

Purpose of the Study:

  • To discover targets of selection and their mutational consequences in E. coli during chronic nutrient limitation.
  • To apply adaptive genetics to identify genes and specific residues under selection pressure.
  • To map gene structure-function relationships in evolving microbial systems.

Main Methods:

  • Culturing replicate E. coli populations for over 300 generations in glucose-limited chemostats.
  • Performing whole-genome, whole-population sequencing every 50 generations at 1000X coverage.
  • Identifying mutations reaching at least 1% frequency to pinpoint targets of selection.

Main Results:

  • Identified 39 high-value genes frequently mutated, far exceeding chance expectation.
  • A majority of these genes encode regulatory proteins controlling gene expression at multiple levels.
  • Recurrent mutations cluster at sites involved in RNA-protein or protein-protein interactions, affecting both regulatory and structural genes.

Conclusions:

  • Experimental evolution coupled with sequencing validates inferences from traditional molecular genetics.
  • Adaptive genetics effectively identifies genes conferring selective advantages and specific residues involved in adaptation.
  • This approach provides insights into the 'why' and 'how' of specific selective advantages conferred by mutations.