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Long-term survival during stationary phase: evolution and the GASP phenotype

Key Points

  • The bacterial life cycle includes five phases. Traditionally, the life cycle of bacteria in the laboratory is described as having three phases: lag, exponential and stationary phases. However, when batch cultures are incubated for longer periods of time there are two additional phases: death phase and long-term stationary phase.

  • During long-term stationary phase, cells expressing the growth advantage in stationary phase (GASP) phenotype emerge. GASP mutations confer a competitive ability to cells during stationary phase.

  • The best-characterized GASP mutations are in rpoS. Although mutations in rpoS are not required for expression of the GASP phenotype, mutations that reduce, but do not eliminate, RpoS activity are frequently associated with the expression of GASP.

  • Long-term stationary-phase cultures are dynamic. The appearance of GASP mutants reflects the fact that stationary-phase cultures are highly dynamic, with new genotypes constantly appearing over time.

  • Mutation frequency can increase during long-term stationary phase. Virtually all long-term batch cultures of Escherichia coli express the GASP phenotype. Furthermore, molecular and genetic methods have shown a wide variety of mutations throughout the chromosome during stationary phase, indicating that mutation frequency is increased during stationary phase, perhaps as a stress response.

  • The methyl-directed mismatch repair system and the error-prone DNA polymerases might have a role in the generation of genetic diversity during stationary phase. Data from various experiments indicate that the modulation of the activity of these two systems can help the cell to regulate the degree of fidelity of replication and repair. Under conditions in which the cell senses significant stress, this alteration of mutation frequency can be viewed as a stress response.

  • The ability to observe evolution in a test tube in real time might reflect processes that are occurring in natural environments. Incubating bacteria under suboptimal conditions can provide an insight into the stress responses that are active in real-world environments. Unlike the standard incubation protocols in which nutrients are usually in abundance, stationary-phase incubation conditions better simulate the stresses of natural environments. The processes leading to the expression of the GASP phenotype might reflect the mechanisms of generation of genetic diversity used by a wide variety of organisms.


The traditional view of the stationary phase of the bacterial life cycle, obtained using standard laboratory culture practices, although useful, might not always provide us with the complete picture. Here, the traditional three phases of the bacterial life cycle are expanded to include two additional phases: death phase and long-term stationary phase. In many natural environments, bacteria probably exist in conditions more akin to those of long-term stationary-phase cultures, in which the expression of a wide variety of stress-response genes and alternative metabolic pathways is essential for survival. Furthermore, stressful environments can result in selection for mutants that express the growth advantage in stationary phase (GASP) phenotype.

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Figure 1: The five phases of the bacterial life cycle.
Figure 2: Four 'flavours' of growth advantage in stationary phase (GASP) phenotypes.
Figure 3: Population dynamics of long-term stationary-phase cultures.
Figure 4: Morphologies of cells isolated from long-term stationary-phase batch cultures.


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The author is greatly indebted to R. Kolter, in whose laboratory his studies of long-term stationary phase were initiated, to S. Nair, G. O'Toole, V. Palchevskiy, E. Pepper, E. Zinser and three anonymous reviews for helpful comments and discussions, and to K. Sivaraman for assistance in the preparation of the manuscript. Work in the author's laboratory is supported in part by a grant from the W. M. Keck Foundation and a National Science Foundation CAREER award.

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Batch culture

A closed culture system in which all of the nutrient substrate is added at the beginning.

Quorum sensing

A system by which bacteria communicate. Signalling molecules — chemicals similar to pheromones that are produced by an individual bacterium — can affect the behaviour of surrounding bacteria.


Paired loci found in the chromosomes of almost all free-living prokaryotes, and many plasmids and phage genomes, encoding a toxin and its antidote that have been proposed to function in bacterial programmed cell death or stress physiology.

Serial passage

An experimental evolution culture system in which a fraction of a culture is sampled and inoculated into a fresh culture of the same medium repeatedly. Over time, cells propagated in this way will show changes in genotype and phenotype associated with changes in relative fitness.

Alternative sigma (σ) factor

Alternative σ factors are produced under specific conditions and allow the RNA polymerase to transcribe a different set of genes than the housekeeping σ factor, σ70.


A mutation between two pyrimidines (T–C) or two purines (A–G).


A point mutation in which a purine base is substituted for a pyrimidine base and vice versa; for example, an AT to CG transversion.


A device that allows the continuous growth of a bacterial population on a growth-rate-limiting resource. The resource flows into the chemostat at a constant rate; depleted medium and cells are washed out at the same rate. The population grows and consumes the resource until the bacteria reach an equilibrium density at which their growth rate equals the flow rate through the vessel.

Very short patch repair

A mismatch-correction system that corrects T:G mismatches to C:G in certain sequence contexts, independent of Dam methylation.

SOS response

The bacterial response to DNA damage that is regulated by the LexA and RecA proteins and involves the expression of a network of >40 genes, including several DNA-repair enzymes.

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Finkel, S. Long-term survival during stationary phase: evolution and the GASP phenotype. Nat Rev Microbiol 4, 113–120 (2006).

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