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Resilient circadian oscillator revealed in individual cyanobacteria


Circadian oscillators, which provide internal daily periodicity, are found in a variety of living organisms, including mammals, insects, plants, fungi and cyanobacteria1. Remarkably, these biochemical oscillators are resilient to external and internal modifications, such as temperature and cell division cycles. They have to be ‘fluctuation (noise) resistant’2 because relative fluctuations in the number of messenger RNA and protein molecules forming the intracellular oscillators are likely to be large. In multicellular organisms, the strong temporal stability of circadian clocks, despite molecular fluctuations, can easily be explained by intercellular interactions3,4,5. Here we study circadian rhythms and their stability in unicellular cyanobacteria Synechoccocus elongatus. Low-light-level microscopy has allowed us to measure gene expression under circadian control in single bacteria, showing that the circadian clock is indeed a property of individual cells. Our measurements show that the oscillators have a strong temporal stability with a correlation time of several months. In contrast to many circadian clocks in multicellular organisms, this stability seems to be ensured by the intracellular biochemical network, because the interactions between oscillators seem to be negligible.

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Figure 1: Circadian oscillation of bioluminescence in individual bacteria.
Figure 2: Growing micro-colonies of cyanobacteria, oscillating with different phases.
Figure 3: Temporal evolution of individual oscillators' phase is independent of close proximity.


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We thank S. Golden for the AMC412 strain and for advice, D. Peoples for advice and technical assistance, B. Houchmandzadeh, J. Paulsson, J. Vilar, C. Weitz and M. Young for discussions, and N. Questembert-Balaban, E. Kussell and M. Vallade for comments on the manuscript. This work was supported partially by Princeton University through the Lewis Thomas Fellowship (I.M.), the National Institutes of Health, the Howard Hughes Medical Institute and the Centre National de Recherche Scientifique through an ATIP and an AC ‘Dynamique et réactivité des assemblages biologiques’.

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Correspondence to Irina Mihalcescu.

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Supplementary Discussion

This has four sections containing discussions and Supplementary Figures S1 to S7. 1. Circadian oscillations of individual bacteria; 2. Estimation of the oscillator noise; 3. Extraction of the detection noise; 4. Detection limit of the coupling strength between oscillators. (PDF 1599 kb)

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Mihalcescu, I., Hsing, W. & Leibler, S. Resilient circadian oscillator revealed in individual cyanobacteria. Nature 430, 81–85 (2004).

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