Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Timing the day: what makes bacterial clocks tick?

Key Points

  • Bacteria exhibit daily timekeeping capabilities, including bona fide circadian rhythmicity.

  • Circadian clock mechanisms in cyanobacteria are the best characterized in terms of biochemistry and biophysics, owing to an in vitro oscillating system that is composed of three clock proteins, as well as complete 3D structures of these proteins.

  • The timekeeping systems in cyanobacteria and purple bacteria confer fitness advantages to these organisms in rhythmic environments.

  • Comparisons between timekeeping mechanisms in cyanobacteria and other bacteria suggest selective forces and stages by which circadian rhythmicity might have evolved.

  • Reciprocal interactions between host and microbiome have an important temporal dimension that is just beginning to be appreciated.

Abstract

Chronobiological studies of prokaryotic organisms have generally lagged far behind the study of endogenous circadian clocks in eukaryotes, in which such systems are essentially ubiquitous. However, despite only being studied during the past 25 years, cyanobacteria have become important model organisms for the study of circadian rhythms and, presently, their timekeeping mechanism is the best understood of any system in terms of biochemistry, structural biology, biophysics and adaptive importance. Nevertheless, intrinsic daily rhythmicity among bacteria other than cyanobacteria is essentially unknown; some tantalizing information suggests widespread daily timekeeping among Eubacteria and Archaea through mechanisms that share common elements with the cyanobacterial clock but are distinct. Moreover, the recent surge of information about microbiome–host interactions has largely neglected the temporal dimension and yet daily cycles control important aspects of their relationship.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Many bacteria are exposed to daily selective pressures.
Figure 2: Circadian molecular and genetic oscillators in cyanobacteria.
Figure 3: The post-translational oscillator (PTO).
Figure 4: KaiC phosphorylation temporal patterns differ between complete circadian clocks that consist of KaiA–KaiB–KaiC and proto-circadian KaiB–KaiC systems.
Figure 5: Criteria for testing the adaptive fitness of daily timekeeping mechanisms.
Figure 6: A hypothesis for the evolution of Kai-based timekeepers in bacteria.

Similar content being viewed by others

References

  1. Grobbelaar, N., Huang, T., Lin, H. & Chow, T. Dinitrogen-fixing endogenous rhythm in Synechococcus RF-1. FEMS Microbiol. Lett. 37, 173–177 (1986). This is the first persuasive report of a circadian rhythm expressed by a bacterium.

    CAS  Google Scholar 

  2. 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). This paper establishes the cyanobacterial circadian system that has been so productive in understanding the mechanism and adaptive importance of circadian rhythms.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Johnson, C. H., Golden, S. S., Ishiura, M. & Kondo, T. Circadian clocks in prokaryotes. Mol. Microbiol. 21, 5–11 (1996).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  5. Ito, H. et al. Cyanobacterial daily life with Kai-based circadian and diurnal genome-wide transcriptional control in Synechococcus elongatus. Proc. Natl Acad. Sci. USA 106, 14168–14173 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Vijayan, V., Zuzow, R. & O'Shea, E. K. Oscillations in supercoiling drive circadian gene expression in cyanobacteria. Proc. Natl Acad. Sci. USA 106, 22564–22568 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Guerreiro, A. C. et al. Daily rhythms in the cyanobacterium Synechococcus elongatus probed by high-resolution mass spectrometry-based proteomics reveals a small defined set of cyclic proteins. Mol. Cell. Proteomics 13, 2042–2055 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. 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).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Dong, G. et al. Elevated ATPase activity of KaiC applies a circadian checkpoint on cell division in Synechococcus elongatus. Cell 140, 529–539 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Woelfle, M. A., Xu, Y., Qin, X. & Johnson, C. H. Circadian rhythms of superhelical status of DNA in cyanobacteria. Proc. Natl Acad. Sci. USA 104, 18819–18824 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Smith, R. M. & Williams, S. B. Circadian rhythms in gene transcription imparted by chromosome compaction in the cyanobacterium Synechococcus elongatus. Proc. Natl Acad. Sci. USA 103, 8564–8569 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Diamond, S., Jun, D., Rubin, B. E. & Golden, S. S. The circadian oscillator in Synechococcus elongatus controls metabolite partitioning during diurnal growth. Proc. Natl Acad. Sci. USA 112, E1916–E1925 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Mitsui, A. et al. Strategy by which nitrogen-fixing unicellular cyanobacteria grow photoautotrophically. Nature 323, 720–722 (1986).

    CAS  Google Scholar 

  14. Ma, P., Mori, T., Zhao, C., Thiel, T. & Johnson, C. H. Evolution of KaiC-dependent timekeepers: a proto-circadian timing mechanism confers adaptive fitness in the purple bacterium Rhodopseudomonas palustris. PLoS Genet. 12, e1005922 (2016). This paper reports daily timekeepers that might not be circadian and also establishes an alternative fitness tests for biological timers.

    PubMed  PubMed Central  Google Scholar 

  15. Robertson, J. B., Davis, C. R. & Johnson, C. H. Visible light alters yeast metabolic rhythms by inhibiting respiration. Proc. Natl Acad. Sci. USA 110, 21130–21135 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Pittendrigh, C. S. Temporal organization: reflections of a Darwinian clock-watcher. Annu. Rev. Physiol. 55, 17–54 (1993).

    Google Scholar 

  17. Nikaido, S. S. & Johnson, C. H. Daily and circadian variation in survival from ultraviolet radiation in Chlamydomonas reinhardtii. Photochem. Photobiol. 71, 758–765 (2000).

    CAS  PubMed  Google Scholar 

  18. Chang, Y.-G. et al. A protein fold switch joins the circadian oscillator to clock output in cyanobacteria. Science 349, 324–328 (2015). This study of the biochemical oscillator of the cyanobacterial clock unveils a substantial conformational change in the KaiB protein prior to its binding to KaiC.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Abe, J. et al. Atomic-scale origins of slowness in the cyanobacterial circadian clock. Science 349, 312–316 (2015). This study provides the first biochemical explanation of how circadian clockwork can have such a long (slow) time constant of approximately 24 hours.

    CAS  PubMed  Google Scholar 

  20. Paulose, J. K., Wright, J. M., Patel, A. G. & Cassone, V. M. Human gut bacteria are sensitive to melatonin and express endogenous circadian rhythmicity. PLoS ONE 11, e0146643 (2016). A new study that reports a gut bacterium that seems to exhibit daily rhythms when isolated outside of the host.

    PubMed  PubMed Central  Google Scholar 

  21. Zarrinpar, A., Chaix, A., Yooseph, S. & Panda, S. Diet and feeding pattern affect the diurnal dynamics of the gut microbiome. Cell Metab. 20, 1006–1017 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Leone, V. et al. Effects of diurnal variation of gut microbes and high-fat feeding on host circadian clock function and metabolism. Cell Host Microbe 17, 681–689 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Voigt, R. M. et al. Circadian disorganization alters intestinal microbiota. PLoS ONE 9, e97500 (2014). This study shows that disruption of the host circadian system alters the composition of the gut microbiome.

    PubMed  PubMed Central  Google Scholar 

  24. Thaiss, C. A. et al. Transkingdom control of microbiota diurnal oscillations promotes metabolic homeostasis. Cell 159, 514–529 (2014).

    CAS  PubMed  Google Scholar 

  25. Liang, X., Bushman, F. D. & FitzGerald, G. A. Rhythmicity of the intestinal microbiota is regulated by gender and the host circadian clock. Proc. Natl Acad. Sci. USA 112, 10479–10484 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Edgar, R. S. et al. Peroxiredoxins are conserved markers of circadian rhythms. Nature 485, 459–464 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Lu, Y. et al. Regulation of the cyanobacterial circadian clock by electrochemically controlled extracellular electron transfer. Angew. Chem. Int. Ed. Engl. 53, 2208–2211 (2014).

    CAS  PubMed  Google Scholar 

  28. Rust, M. J., Golden, S. S. & O'Shea, E. K. Light-driven changes in energy metabolism directly entrain the cyanobacterial circadian oscillator. Science 331, 220–223 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Kim, Y.-I., Vinyard, D. J., Ananyev, G. M., Dismukes, G. C. & Golden, S. S. Oxidized quinones signal onset of darkness directly to the cyanobacterial circadian oscillator. Proc. Natl Acad. Sci. USA 109, 17765–17769 (2012). References 28 and 29 show that environmental resetting of the cyanobacterial clock seems to be mediated by daily light-driven and dark-driven driven changes in intracellular ATP and/or redox levels.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Cohen, S. E. & Golden, S. S. Circadian rhythms in cyanobacteria. Microbiol. Mol. Biol. Rev. 79, 373–385 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Pattanayak, G. K., Phong, C. & Rust, M. J. Rhythms in energy storage control the ability of the cyanobacterial circadian clock to reset. Curr. Biol. 24, 1934–1938 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Johnson, C. H. & Egli, M. Metabolic compensation and circadian resilience in prokaryotic cyanobacteria. Annu. Rev. Biochem. 83, 221 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Hardin, P. E., Hall, J. C. & Rosbash, M. Feedback of the Drosophila period gene product on circadian cycling of its messenger RNA levels. Nature 343, 536–540 (1990).

    CAS  PubMed  Google Scholar 

  34. Aronson, B. D., Johnson, K. A., Loros, J. J. & Dunlap, J. C. Negative feedback defining a circadian clock: autoregulation of the clock gene frequency. Science 263, 1578–1584 (1994).

    CAS  PubMed  Google Scholar 

  35. Dibner, C. et al. Circadian gene expression is resilient to large fluctuations in overall transcription rates. EMBO J. 28, 123–134 (2009).

    CAS  PubMed  Google Scholar 

  36. Johnson, C. H. Circadian clocks and cell division: what's the pacemaker? Cell Cycle 9, 3864–3873 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Egli, M. & Johnson, C. H. A circadian clock nanomachine that runs without transcription or translation. Curr. Opin. Neurobiol. 23, 732–740 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Ishiura, M. et al. Expression of a gene cluster kaiABC as a circadian feedback process in cyanobacteria. Science 281, 1519–1523 (1998).

    CAS  PubMed  Google Scholar 

  39. Nakajima, M. et al. Reconstitution of circadian oscillation of cyanobacterial KaiC phosphorylation in vitro. Science 308, 414–415 (2005). This study details a unique reconstitution of a circadian biochemical oscillator in vitro with three purified clock proteins from cyanobacteria.

    CAS  PubMed  Google Scholar 

  40. Kitayama, Y., Nishiwaki, T., Terauchi, K. & Kondo, T. Dual KaiC-based oscillations constitute the circadian system of cyanobacteria. Genes Dev. 22, 1513–1521 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Qin, X. et al. Intermolecular associations determine the dynamics of the circadian KaiABC oscillator. Proc. Natl Acad. Sci. USA 107, 14805–14810 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Johnson, C. H., Egli, M. & Stewart, P. L. Structural insights into a circadian oscillator. Science 322, 697–701 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Hosokawa, N., Kushige, H. & Iwasaki, H. Attenuation of the posttranslational oscillator via transcription–translation feedback enhances circadian-phase shifts in Synechococcus. Proc. Natl Acad. Sci. USA 110, 14486–14491 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Pattanayek, R. et al. Visualizing a circadian clock protein: crystal structure of KaiC and functional insights. Mol. Cell 15, 375–388 (2004). This study reports the 3D structure of the core cyanobacterial clock protein, as well as the identification of the first phosphorylation site that regulates its function.

    CAS  PubMed  Google Scholar 

  45. Terauchi, K. et al. ATPase activity of KaiC determines the basic timing for circadian clock of cyanobacteria. Proc. Natl Acad. Sci. USA 104, 16377–16381 (2007). This study details the discovery of the key rate-limiting reaction in KaiC that determines circadian period.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Nishiwaki, T. et al. A sequential program of dual phosphorylation of KaiC as a basis for circadian rhythm in cyanobacteria. EMBO J. 26, 4029–4037 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Rust, M. J., Markson, J. S., Lane, W. S., Fisher, D. S. & O'Shea, E. K. Ordered phosphorylation governs oscillation of a three-protein circadian clock. Science 318, 809–812 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Xu, Y. et al. Identification of key phosphorylation sites in the circadian clock protein KaiC by crystallographic and mutagenetic analyses. Proc. Natl Acad. Sci. USA 101, 13933–13938 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Pattanayek, R. et al. Structures of KaiC circadian clock mutant proteins: a new phosphorylation site at T426 and mechanisms of kinase, ATPase and phosphatase. PLoS ONE 4, e7529 (2009).

    PubMed  PubMed Central  Google Scholar 

  50. Xu, Y. et al. Intramolecular regulation of phosphorylation status of the circadian clock protein KaiC. PLoS ONE 4, e7509 (2009).

    PubMed  PubMed Central  Google Scholar 

  51. Tomita, J., Nakajima, M., Kondo, T. & Iwasaki, H. No transcription–translation feedback in circadian rhythm of KaiC phosphorylation. Science 307, 251–254 (2005). This study contains the first definitive evidence that indicates that the cyanobacterial clock system might not be based on a TTFL loop.

    CAS  PubMed  Google Scholar 

  52. Xu, Y., Mori, T. & Johnson, C. H. Circadian clock protein expression in cyanobacteria: rhythms and phase setting. EMBO J. 19, 3349–3357 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Iwasaki, H., Nishiwaki, T., Kitayama, Y., Nakajima, M. & Kondo, T. KaiA-stimulated KaiC phosphorylation in circadian timing loops in cyanobacteria. Proc. Natl Acad. Sci. USA 99, 15788–15793 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Williams, S. B., Vakonakis, I., Golden, S. S. & LiWang, A. C. Structure and function from the circadian clock protein KaiA of Synechococcus elongatus: a potential clock input mechanism. Proc. Natl Acad. Sci. USA 99, 15357–15362 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Kim, Y.-I., Dong, G., Carruthers, C. W., Golden, S. S. & LiWang, A. The day/night switch in KaiC, a central oscillator component of the circadian clock of cyanobacteria. Proc. Natl Acad. Sci. USA 105, 12825–12830 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Pattanayek, R. & Egli, M. Protein–protein interactions in the cyanobacterial circadian clock: structure of KaiA dimer in complex with C-terminal KaiC peptides at 2.8 Å resolution. Biochemistry 54, 4575–4578 (2015).

    CAS  PubMed  Google Scholar 

  57. Egli, M. et al. Dephosphorylation of the core clock protein KaiC in the cyanobacterial KaiABC circadian oscillator proceeds via an ATP synthase mechanism. Biochemistry 51, 1547–1558 (2012).

    CAS  PubMed  Google Scholar 

  58. Nishiwaki, T. & Kondo, T. Circadian autodephosphorylation of cyanobacterial clock protein KaiC occurs via formation of ATP as intermediate. J. Biol. Chem. 287, 18030–18035 (2012). References 57 and 58 report the remarkable result that KaiC seems to regenerate ATP from ADP as it dephosphorylates.

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Kageyama, H. et al. Cyanobacterial circadian pacemaker: Kai protein complex dynamics in the KaiC phosphorylation cycle in vitro. Mol. Cell 23, 161–171 (2006).

    CAS  PubMed  Google Scholar 

  60. Mori, T. et al. Elucidating the ticking of an in vitro circadian clockwork. PLoS Biol. 5, e93 (2007).

  61. Lin, J., Chew, J., Chockanathan, U. & Rust, M. J. Mixtures of opposing phosphorylations within hexamers precisely time feedback in the cyanobacterial circadian clock. Proc. Natl Acad. Sci. USA 111, E3937–E3945 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Vakonakis, I. & LiWang, A. C. Structure of the C-terminal domain of the clock protein KaiA in complex with a KaiC-derived peptide: implications for KaiC regulation. Proc. Natl Acad. Sci. USA 101, 10925–10930 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Nishiwaki-Ohkawa, T., Kitayama, Y., Ochiai, E. & Kondo, T. Exchange of ADP with ATP in the CII ATPase domain promotes autophosphorylation of cyanobacterial clock protein KaiC. Proc. Natl Acad. Sci. USA 111, 4455–4460 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Espinosa, J. et al. Cross-talk and regulatory interactions between the essential response regulator RpaB and cyanobacterial circadian clock output. Proc. Natl Acad. Sci. USA 112, 2198–2203 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Markson, J. S., Piechura, J. R., Puszynska, A. M. & O'Shea, E. K. Circadian control of global gene expression by the cyanobacterial master regulator RpaA. Cell 155, 1396–1408 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Takai, N. et al. A KaiC-associating SasA–RpaA two-component regulatory system as a major circadian timing mediator in cyanobacteria. Proc. Natl Acad. Sci. USA 103, 12109–12114 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Taniguchi, Y., Takai, N., Katayama, M., Kondo, T. & Oyama, T. Three major output pathways from the KaiABC-based oscillator cooperate to generate robust circadian kaiBC expression in cyanobacteria. Proc. Natl Acad. Sci. USA 107, 3263–3268 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Iwasaki, H. et al. A KaiC-interacting sensory histidine kinase, SasA, necessary to sustain robust circadian oscillation in cyanobacteria. Cell 101, 223–233 (2000).

    CAS  PubMed  Google Scholar 

  69. Pattanayek, R. et al. Combined SAXS/EM based models of the S. elongatus post-translational circadian oscillator and its interactions with the output His-kinase SasA. PLoS ONE 6, e23697 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Iida, T. et al. Importance of the monomer–dimer–tetramer interconversion of the clock protein KaiB in the generation of circadian oscillations in cyanobacteria. Genes Cells 20, 173–190 (2015).

    CAS  PubMed  Google Scholar 

  71. Qin, X., Byrne, M., Xu, Y., Mori, T. & Johnson, C. H. Coupling of a core post-translational pacemaker to a slave transcription/translation feedback loop in a circadian system. PLoS Biol. 8, e1000394 (2010).

    PubMed  PubMed Central  Google Scholar 

  72. Teng, S.-W., Mukherji, S., Moffitt, J. R., De Buyl, S. & O'Shea, E. K. Robust circadian oscillations in growing cyanobacteria require transcriptional feedback. Science 340, 737–740 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Zwicker, D., Lubensky, D. K. & ten Wolde, P. R. Robust circadian clocks from coupled protein-modification and transcription–translation cycles. Proc. Natl Acad. Sci. USA 107, 22540–22545 (2010). References 71–73 show that the coupled PTO and TTFL oscillator systems in cyanobacteria promote an emergent robustness.

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  75. Ito, H. et al. Autonomous synchronization of the circadian KaiC phosphorylation rhythm. Nat. Struct. Mol. Biol. 14, 1084–1088 (2007). This paper reports the remarkable ability of the KaiA–KaiB–KaiC in vitro oscillator to maintain itself without damping for 10 or more days.

    CAS  PubMed  Google Scholar 

  76. Kitayama, Y., Nishiwaki-Ohkawa, T., Sugisawa, Y. & Kondo, T. KaiC intersubunit communication facilitates robustness of circadian rhythms in cyanobacteria. Nat. Commun. 4, 2897 (2013).

    PubMed  Google Scholar 

  77. Loza-Correa, M., Gomez-Valero, L. & Buchrieser, C. Circadian clock proteins in prokaryotes: hidden rhythms? Front. Microbiol. 1, 130 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Dvornyk, V., Vinogradova, O. & Nevo, E. Origin and evolution of circadian clock genes in prokaryotes. Proc. Natl Acad. Sci. USA 100, 2495–2500 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Holtzendorff, J. et al. Genome streamlining results in loss of robustness of the circadian clock in the marine cyanobacterium Prochlorococcus marinus PCC 9511. J. Biol. Rhythms 23, 187–199 (2008).

    CAS  PubMed  Google Scholar 

  80. Zinser, E. R. et al. Choreography of the transcriptome, photophysiology, and cell cycle of a minimal photoautotroph, Prochlorococcus. PLoS ONE 4, e5135 (2009).

    PubMed  PubMed Central  Google Scholar 

  81. Axmann, I. M. et al. Biochemical evidence for a timing mechanism in Prochlorococcus. J. Bacteriol. 191, 5342–5347 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Mullineaux, C. W. & Stanewsky, R. The rolex and the hourglass: a simplified circadian clock in Prochlorococcus? J. Bacteriol. 191, 5333–5335 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Whitehead, K., Pan, M., Masumura, K., Bonneau, R. & Baliga, N. S. Diurnally entrained anticipatory behavior in archaea. PLoS ONE 4, e5485 (2009).

    PubMed  PubMed Central  Google Scholar 

  84. Min, H., Guo, H. & Xiong, J. Rhythmic gene expression in a purple photosynthetic bacterium, Rhodobacter sphaeroides. FEBS Lett. 579, 808–812 (2005).

    CAS  PubMed  Google Scholar 

  85. Woelfle, M. A., Ouyang, Y., Phanvijhitsiri, K. & Johnson, C. H. The adaptive value of circadian clocks: an experimental assessment in cyanobacteria. Curr. Biol. 14, 1481–1486 (2004).

    CAS  PubMed  Google Scholar 

  86. Ouyang, Y., Andersson, C. R., Kondo, T., Golden, S. S. & Johnson, C. H. Resonating circadian clocks enhance fitness in cyanobacteria. Proc. Natl Acad. Sci. USA 95, 8660–8664 (1998). References 85 and 86 provide the first rigorous tests of the adaptive fitness that is conferred by circadian timing in any organism and establish the competition assay as a fitness test for circadian systems.

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Roenneberg, T. & Merrow, M. Life before the clock: modeling circadian evolution. J. Biol. Rhythms 17, 495–505 (2002).

    PubMed  Google Scholar 

  88. Troein, C., Locke, J. C., Turner, M. S. & Millar, A. J. Weather and seasons together demand complex biological clocks. Curr. Biol. 19, 1961–1964 (2009).

    CAS  PubMed  Google Scholar 

  89. Maurice, C. F. et al. Marked seasonal variation in the wild mouse gut microbiota. ISME J. 9, 2423–2434 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Donia, M. S. & Fischbach, M. A. Small molecules from the human microbiota. Science 349, 1254766 (2015).

    PubMed  PubMed Central  Google Scholar 

  91. Mukamolova, G. V., Kaprelyants, A. S., Young, D. I., Young, M. & Kell, D. B. A bacterial cytokine. Proc. Natl Acad. Sci. USA 95, 8916–8921 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Thaiss, C. A. et al. Microbiota diurnal rhythmicity programs host transcriptome oscillations. Cell 167, 1495–1510 (2016). This study finds that disruption of the microbiome by antibiotics feeds back on the host.

    CAS  PubMed  Google Scholar 

  93. McFall-Ngai, M. Divining the essence of symbiosis: insights from the squid-vibrio model. PLoS Biol. 12, e1001783 (2014).

    PubMed  PubMed Central  Google Scholar 

  94. Boettcher, K. J., Ruby, E. G. & McFall-Ngai, M. J. Bioluminescence in the symbiotic squid Euprymna scolopes is controlled by a daily biological rhythm. J. Comp. Physiol. 179, 65–73 (1996).

    Google Scholar 

  95. Wier, A. M. et al. Transcriptional patterns in both host and bacterium underlie a daily rhythm of anatomical and metabolic change in a beneficial symbiosis. Proc. Natl Acad. Sci. USA 107, 2259–2264 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Millar, A. J., Short, S. R., Chua, N.-H. & Kay, S. A. A novel circadian phenotype based on firefly luciferase expression in transgenic plants. Plant Cell 4, 1075–1087 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Yamazaki, S. et al. Resetting central and peripheral circadian oscillators in transgenic rats. Science 288, 682–685 (2000).

    CAS  PubMed  Google Scholar 

  98. Dunlap, J. C., Loros, J. J. & DeCoursey, P. J. Chronobiology: Biological Timekeeping (Sinauer Associates, 2004).

    Google Scholar 

  99. Njus, D., McMurry, L. & Hastings, J. W. Conditionality of circadian rhythmicity: synergistic action of light and temperature. J. Comp. Physiol. 117, 335–344 (1977).

    Google Scholar 

  100. Xu, Y. et al. Non-optimal codon usage is a mechanism to achieve circadian clock conditionality. Nature 495, 116–120 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  101. Johnson, C. H., Mori, T. & Xu, Y. A cyanobacterial circadian clockwork. Curr. Biol. 18, R816–R825 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors dedicate this paper to the memory of their colleague and friend D. McCauley, a population geneticist who encouraged and facilitated their tests on the adaptive fitness of circadian clocks in microorganisms. The authors thank T. Kondo, S. Golden and M. Ishiura (and past and present members of their laboratories), as well as past and present members of the laboratory of C.H.J., for an exhilarating scientific journey into the circadiana of cyanobacteria. This research in the laboratory of C.H.J. is currently supported by grants from the US National Institutes of Health (GM 067152 and GM107434).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Carl Hirschie Johnson.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

PowerPoint slides

Glossary

Diurnal

Active during the day.

Nocturnal

Active during the night.

Hourglass timer

A simple non-oscillatory timer that is set in motion and keeps track of time linearly, and thus does not self-sustain a cycle.

Photoautotrophic bacteria

Bacteria that derive their energy exclusively from light to drive photosynthetic carbon fixation and the synthesis of organic compounds.

Proto-circadian

A broad term that includes hourglass timers, damped oscillators and other potential timekeeping mechanisms that may be ancestral systems that include some, but not necessarily all, of the canonical properties of circadian clocks. Proto-circadian systems may be a step along an evolutionary trajectory that might ultimately lead to a bona fide circadian system.

Peroxiredoxins

A class of antioxidant enzymes that control peroxide levels.

Entrain

The process whereby the period of a biological rhythm becomes equal to that of an environmental cycle (for example, of light and dark). Entrainment also establishes a stable phase relationship between the entraining cycle and the biological rhythm.

Ectotherms

'Cold-blooded' animals in which the body temperature depends on the environmental temperature but is often modulated behaviourally.

Halophilic

Adapted to high concentrations of salt.

Endothermic

'Warm-blooded', that is, the maintenance of body temperature metabolically so that it is independent of the environment and behaviour.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Johnson, C., Zhao, C., Xu, Y. et al. Timing the day: what makes bacterial clocks tick?. Nat Rev Microbiol 15, 232–242 (2017). https://doi.org/10.1038/nrmicro.2016.196

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrmicro.2016.196

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing