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Cell individuality: the bistability of competence development

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Heterogeneous development of competence among cells of the bacterium Bacillus subtilis provides an appealing model of cell individuality, an area that is currently attracting considerable research interest. Under appropriate conditions, only a fraction of cells in an isogenic culture become competent for transformation. Two experimental studies have now pinpointed the same auto-stimulatory feedback loop of gene expression as the principal requirement for the establishment of this ‘bistable’ response.

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Phenotypic heterogeneity

Would a world in which all organisms of a population behaved in the same ‘optimized’ way necessarily be a better one? Evidently not. Phenotypic diversity is manifest in all organisms and in microorganisms it is readily apparent among individual cells even within isogenic populations. The benefits of such non-genotype-derived heterogeneity are likely to lie in the enhanced adaptability and hardiness of the population as a whole; promoting the chances that better-adapted phenotypic variants might

Regulatory requirements for heterogeneity in competence development

Two recently published studies of competence development in B. subtilis have helped to crystallize our understanding of the development of bistable expression states. Smits et al. [10] dissected out the various regulatory inputs to the natural signal transduction cascade that determines competence development. Similar tools were used by Maamar and Dubnau but with a focus on discriminating between two models of bistability development [9]. A major conclusion derived from both experimental

The underlying source of heterogeneity

Although protection against MecA-dependent degradation in the previous experiments increased the proportion of cells that developed competence, it did not abolish heterogeneity, consistent with this property being dependent on auto-stimulation of comK expression alone. This leads to another fundamental question, which is common to many studies of heterogeneity but for which an answer has, thus far, eluded many: what determines which cells reach the threshold? (i.e. why does the basal level of

The future

The current pace of progress in the field of cell individuality gives confidence that certain enduring experimental obstacles will be resolved in the near future. The recent introduction of dual fluorescent reporters to monitor the source of ‘noise’ in gene expression [18] and optical well arrays for temporal single-cell fluorescence measurements [19], already offers far greater insight than was previously possible (Box 1). Moreover, although it was stressed at the outset that the potential

Acknowledgements

I gratefully acknowledge the support of the NIH (R01 GM57945), the BBSRC (BB/C506656/1) and the NERC (NER/B/S/2003/00730) for heterogeneity-related work.

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