Bet-hedging and epigenetic inheritance in bacterial cell development

Molecular Genetics Group, Groningen Biomolecular Sciences and Biotechnology Institute, and Theoretical Biology Group, Centre for Ecological and Evolutionary Studies, University of Groningen, 9751 NN, Haren, The Netherlands.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 04/2008; 105(11):4393-8. DOI: 10.1073/pnas.0700463105
Source: PubMed


Upon nutritional limitation, the bacterium Bacillus subtilis has the capability to enter the irreversible process of sporulation. This developmental process is bistable, and only a subpopulation of cells actually differentiates into endospores. Why a cell decides to sporulate or not to do so is poorly understood. Here, through the use of time-lapse microscopy, we follow the growth, division, and differentiation of individual cells to identify elements of cell history and ancestry that could affect this decision process. These analyses show that during microcolony development, B. subtilis uses a bet-hedging strategy whereby some cells sporulate while others use alternative metabolites to continue growth, providing the latter subpopulation with a reproductive advantage. We demonstrate that B. subtilis is subject to aging. Nevertheless, the age of the cell plays no role in the decision of its fate. However, the physiological state of the cell's ancestor (more than two generations removed) does affect the outcome of cellular differentiation. We show that this epigenetic inheritance is based on positive feedback within the sporulation phosphorelay. The extended intergenerational "memory" caused by this autostimulatory network may be important for the development of multicellular structures such as fruiting bodies and biofilms.

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Available from: Oscar Kuipers, Sep 10, 2014
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    • "Bacillus subtilis divides by binary fission to produce identical daughter cells during vegetative growth but switches to asymmetric division when undergoing the developmental process of spore formation (Piggot and Coote, 1976; Stragier and Losick, 1996). To sporulate, cells place a division septum near a randomly chosen pole of the cell (Veening et al., 2008) to create two unequally sized daughter cells with dissimilar programs of gene expression. The smaller cell, the forespore, which largely consists of the cell pole, will become the spore, whereas the larger cell, the mother cell, nurtures the developing spore (Figure 1B). "
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    ABSTRACT: Formation of a division septum near a randomly chosen pole during sporulation in B. subtilis creates unequal sized daughter cells with dissimilar programs of gene expression. An unanswered question is how polar septation activates a transcription factor (σ(F)) selectively in the small cell. We present evidence that the upstream regulator of σ(F), the phosphatase SpoIIE, is compartmentalized in the small cell by transfer from the polar septum to the adjacent cell pole where SpoIIE is protected from proteolysis and activated. Polar recognition, protection from proteolysis, and stimulation of phosphatase activity are linked to oligomerization of SpoIIE. This mechanism for initiating cell-specific gene expression is independent of additional sporulation proteins; vegetative cells engineered to divide near a pole sequester SpoIIE and activate σ(F) in small cells. Thus, a simple model explains how SpoIIE responds to a stochastically-generated cue to activate σ(F) at the right time and in the right place.
    Full-text · Article · Oct 2015 · eLife Sciences
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    • "In the bacterial population , sporulation does not occur homogenously, but rather occurs in subpopulations. Presumably, this is a bet-hedging strategy that allows the cell to absolutely confirm the need to sporulate prior to engaging in this highly energy-consuming and, once committed, irreversible developmental programme (Veening et al., 2008). The first bet-hedging strategy to delay entry into sporulation is the 'cannibalistic' behaviour displayed by a subpopulation of cells that are the first to detect the onset of starvation conditions. "
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    ABSTRACT: Although prokaryotes ordinarily undergo binary fission to produce two identical daughter cells, some are able to undergo alternative developmental pathways that produce daughter cells of distinct cell morphology and fate. One such example is a developmental programme called sporulation in the bacterium Bacillus subtilis, which occurs under conditions of environmental stress. Sporulation has long been used as a model system to help elucidate basic processes of developmental biology including transcription regulation, intercellular signalling, membrane remodelling, protein localization and cell fate determination. This review highlights some of the recent work that has been done to further understand prokaryotic cell differentiation during sporulation and its potential applications.
    Full-text · Article · Jun 2014 · Environmental Microbiology Reports
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    • "Phenotypic variability, including epigenetic inheritance, also plays an important role in the framework of bet-hedging in which variable populations show increased fitness compared with homogeneous populations in fluctuating environments [39], [40]. However, unlike the concept of bet-hedging, in which population variability maintained in a benign environment serves to rescue the population upon a switch to harsh conditions [36], [41], [42], our phenotypic variations represent exploration toward stabilizing a relaxed, adapted state all within a constant environment. "
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    ABSTRACT: Neo-Darwinian evolution has presented a paradigm for population dynamics built on random mutations and selection with a clear separation of time-scales between single-cell mutation rates and the rate of reproduction. Laboratory experiments on evolving populations until now have concentrated on the fixation of beneficial mutations. Following the Darwinian paradigm, these experiments probed populations at low temporal resolution dictated by the rate of rare mutations, ignoring the intermediate evolving phenotypes. Selection however, works on phenotypes rather than genotypes. Research in recent years has uncovered the complexity of genotype-to-phenotype transformation and a wealth of intracellular processes including epigenetic inheritance, which operate on a wide range of time-scales. Here, by studying the adaptation dynamics of genetically rewired yeast cells, we show a novel type of population dynamics in which the intracellular processes intervene in shaping the population structure. Under constant environmental conditions, we measure a wide distribution of growth rates that coexist in the population for very long durations (>100 generations). Remarkably, the fastest growing cells do not take over the population on the time-scale dictated by the width of the growth-rate distributions and simple selection. Additionally, we measure significant fluctuations in the population distribution of various phenotypes: the fraction of exponentially-growing cells, the distributions of single-cell growth-rates and protein content. The observed fluctuations relax on time-scales of many generations and thus do not reflect noisy processes. Rather, our data show that the phenotypic state of the cells, including the growth-rate, for large populations in a constant environment is metastable and varies on time-scales that reflect the importance of long-term intracellular processes in shaping the population structure. This lack of time-scale separation between the intracellular and population processes calls for a new framework for population dynamics which is likely to be significant in a wide range of biological contexts, from evolution to cancer.
    Full-text · Article · Dec 2013 · PLoS ONE
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