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Circadian rhythms persist without transcription in a eukaryote


Circadian rhythms are ubiquitous in eukaryotes, and coordinate numerous aspects of behaviour, physiology and metabolism, from sleep/wake cycles in mammals to growth and photosynthesis in plants1,2. This daily timekeeping is thought to be driven by transcriptional–translational feedback loops, whereby rhythmic expression of ‘clock’ gene products regulates the expression of associated genes in approximately 24-hour cycles. The specific transcriptional components differ between phylogenetic kingdoms3. The unicellular pico-eukaryotic alga Ostreococcus tauri possesses a naturally minimized clock, which includes many features that are shared with plants, such as a central negative feedback loop that involves the morning-expressed CCA1 and evening-expressed TOC1 genes4. Given that recent observations in animals and plants have revealed prominent post-translational contributions to timekeeping5, a reappraisal of the transcriptional contribution to oscillator function is overdue. Here we show that non-transcriptional mechanisms are sufficient to sustain circadian timekeeping in the eukaryotic lineage, although they normally function in conjunction with transcriptional components. We identify oxidation of peroxiredoxin proteins as a transcription-independent rhythmic biomarker, which is also rhythmic in mammals6. Moreover we show that pharmacological modulators of the mammalian clock mechanism have the same effects on rhythms in Ostreococcus. Post-translational mechanisms, and at least one rhythmic marker, seem to be better conserved than transcriptional clock regulators. It is plausible that the oldest oscillator components are non-transcriptional in nature, as in cyanobacteria7, and are conserved across kingdoms.

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Figure 1: Transcriptionally inactive cells show a phase-dependent response to re-illumination.
Figure 2: Circadian cycles of PRX oxidation are detected during light/dark cycles and in constant darkness, and persist during drug inhibition of gene expression.
Figure 3: Circadian timing can survive the inhibition of cellular transcription, or cytosolic translation.
Figure 4: Circadian period in O. tauri can be modulated pharmacologically in a dose-dependent manner by the application of inhibitors that have been previously validated in other taxa.


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CSBE is a Centre for Integrative Systems Biology funded by BBSRC and EPSRC award D019621. C.T. is supported by a BBSRC/ANR joint project F005466 awarded to F.-Y.B. and A.J.M. and by the HFSP. A.B.R. is supported by the Wellcome Trust (083643/Z/07/Z) and the MRC Centre for Obesity and Related metabolic Disorders (MRC CORD).

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J.S.O’N., G.v.O. and L.E.D. designed and performed the experiments; J.S.O’N., G.v.O., L.E.D., C.T., A.B.R. and A.J.M. analysed data. F.-Y.B. and F.C. generated essential protocols and biomaterials. All authors contributed to writing. J.S.O’N. and G.v.O. contributed equally to this paper.

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Correspondence to Akhilesh B. Reddy or Andrew J. Millar.

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The authors declare no competing financial interests.

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O’Neill, J., van Ooijen, G., Dixon, L. et al. Circadian rhythms persist without transcription in a eukaryote. Nature 469, 554–558 (2011).

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