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Resilient circadian oscillator revealed in individual cyanobacteria

Nature volume 430, pages 81–85 (2004)Cite this article

Abstract

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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References

  1. Young, M. W. & Kay, S. A. Time zones: a comparative genetics of circadian clocks. Nature Rev. Genet. 2, 702–715 (2001)

    Article  CAS  Google Scholar 

  2. Barkai, N. & Leibler, S. Circadian clocks limited by noise. Nature 403, 267–268 (2000)

    Article  ADS  CAS  Google Scholar 

  3. Pikovsky, A., Rosenblum, M. & Kurths, J. Synchronization: A Universal Concept in Nonlinear Sciences (Cambridge Univ. Press, Cambridge, 2001)

    Book  Google Scholar 

  4. Liu, C., Weaver, D. R., Strogatz, S. H. & Reppert, S. M. Cellular construction of a circadian clock: period determination in the suprachiasmatic nuclei. Cell 91, 855–860 (1997)

    Article  CAS  Google Scholar 

  5. Yamaguchi, S. et al. Synchronization of cellular clocks in the suprachiasmatic nucleus. Science 302, 1408–1412 (2003)

    Article  ADS  CAS  Google Scholar 

  6. Kondo, T. et al. Circadian rhythms in prokaryotes: luciferase as a reporter of circadian gene expression in cyanobacteria. Proc. Natl Acad. Sci. USA 90, 5672–5676 (1993)

    Article  ADS  CAS  Google Scholar 

  7. Liu, Y. et al. Circadian orchestration of gene expression in cyanobacteria. Genes Dev. 9, 1469–1478 (1995)

    Article  CAS  Google Scholar 

  8. Katayama, M., Tsinoremas, N. F., Kondo, T. & Golden, S. S. cpmA, a gene involved in an output pathway of the cyanobacterial circadian system. J. Bacteriol. 181, 3516–3524 (1999)

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Tsinoremas, N. F., Schaefer, M. R. & Golden, S. S. Blue and red light reversibly control psbA expression in the cyanobacterium Synechococcus sp. strain PCC 7942. J. Biol. Chem. 269, 16143–16147 (1994)

    CAS  PubMed  Google Scholar 

  10. Kondo, T. et al. Circadian rhythms in rapidly dividing cyanobacteria. Science 275, 224–227 (1997)

    Article  CAS  Google Scholar 

  11. Mori, T. & Johnson, C. H. Independence of circadian timing from cell division in cyanobacteria. J. Bacteriol. 183, 2439–2444 (2001)

    Article  CAS  Google Scholar 

  12. Mori, T., Binder, B. & Johnson, C. H. Circadian gating of cell division in cyanobacteria growing with average doubling times of less than 24 hours. Proc. Natl Acad. Sci. USA 93, 10183–10188 (1996)

    Article  ADS  CAS  Google Scholar 

  13. Gaspard, P. The correlation time of mesoscopic chemical clocks. J. Chem. Phys. 117, 8905–8916 (2002)

    Article  ADS  CAS  Google Scholar 

  14. Elowitz, M. B., Levine, A. J., Siggia, E. D. & Swain, P. S. Stochastic gene expression in a single cell. Science 297, 1183–1186 (2002)

    Article  ADS  CAS  Google Scholar 

  15. Kiss, I. Z., Zhai, Y. & Hudson, J. L. Emerging coherence in a population of chemical oscillators. Science 296, 1676–1678 (2002)

    Article  ADS  CAS  Google Scholar 

  16. Levine, J. D., Funes, P., Dowse, H. B. & Hall, J. C. Resetting the circadian clock by social experience in Drosophila melanogaster. Science 298, 2010–2012 (2002)

    Article  ADS  CAS  Google Scholar 

  17. Winfree, A. T. The Geometry of Biological Time, 2nd edn (Springer, New York, 2001)

    Book  Google Scholar 

  18. Goldbeter, A. Computational approaches to cellular rhythms. Nature 420, 238–245 (2002)

    Article  ADS  CAS  Google Scholar 

  19. Gonze, D., Halloy, J. & Goldbeter, A. Robustness of circadian rhythms with respect to molecular noise. Proc. Natl Acad. Sci. USA 99, 673–678 (2002)

    Article  ADS  CAS  Google Scholar 

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Acknowledgements

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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Author notes

  1. Weihong Hsing

    Present address: Johnson & Johnson PRD, PO Box 300, Raritan, New Jersey, 08869, USA

Authors and Affiliations

  1. Laboratoire de Spectrométrie Physique, Université Joseph Fourier – Grenoble I, BP87, 38402, St-Martin d'Hères Cédex, France

    Irina Mihalcescu

  2. Department of Molecular Biology, Princeton University, Princeton, New Jersey, 08544, USA

    Weihong Hsing

  3. Laboratory of Living Matter and Centre for Studies in Physics and Biology, The Rockefeller University, 1230 York Avenue, New York, 10021, USA

    Stanislas Leibler

Authors
  1. Irina Mihalcescu
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  3. Stanislas Leibler
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Correspondence to Irina Mihalcescu.

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The authors declare that they have no competing financial interests.

Supplementary information

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). https://doi.org/10.1038/nature02533

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