Robust, coherent, and synchronized circadian clock-controlled oscillations along Anabaena filaments.

Rinat Arbel-Goren,Ana Valladares,Sergio Camargo,Joel Stavans,Duccio Fanelli,Francesca Di Patti,Antonia Herrero,Valentina Buonfiglio,Enrique Flores,Anna Zhitnitsky

doi:10.7554/elife.64348

Abstract

Circadian clocks display remarkable reliability despite significant stochasticity in biomolecular reactions. We study the dynamics of a circadian clock-controlled gene at the individual cell level in Anabaena sp. PCC 7120, a multicellular filamentous cyanobacterium. We found significant synchronization and spatial coherence along filaments, clock coupling due to cell-cell communication, and gating of the cell cycle. Furthermore, we observed low-amplitude circadian oscillatory transcription of kai genes encoding the post-transcriptional core oscillatory circuit and high-amplitude oscillations of rpaA coding for the master regulator transducing the core clock output. Transcriptional oscillations of rpaA suggest an additional level of regulation. A stochastic one-dimensional toy model of coupled clock cores and their phosphorylation states shows that demographic noise can seed stochastic oscillations outside the region where deterministic limit cycles with circadian periods occur. The model reproduces the observed spatio-temporal coherence along filaments and provides a robust description of coupled circadian clocks in a multicellular organism.

Highlights

Endogenous circadian clocks allow the alignment of cellular physiology with diurnal light/darkness cycles onEarth, endowing organisms, from unicellular cyanobacteria to multicellular plants and mammals, with a selective fitness advantage (Cohen and Golden, 2015)
Salient feature of the circadian clock in Synechococcus is the high temporal precision it can exhibit, despite the fact that biochemical reactions in a cell are stochastic events and that clock components may be subject to variations in molecular copy numbers between cells, variations known as demographic noise (Tsimring, 2014)
In addition to inheritance following cell division as in unicellular Synechococcus (Amdaoud et al, 2007), the behaviors of both the spatial autocorrelation (Fig. 2D), and the complex coherence function (Fig. 6D) represent strong evidence that these two characteristics result from local coupling between clocks of neighboring cells due to cell-cell communication via septal junctions

Summary

Introduction

Endogenous circadian clocks allow the alignment of cellular physiology with diurnal light/darkness cycles onEarth, endowing organisms, from unicellular cyanobacteria to multicellular plants and mammals, with a selective fitness advantage (Cohen and Golden, 2015). The molecular mechanisms behind autonomous circadian clocks have been elucidated primarily in the unicellular Synechococcus elongatus. These investigations have shown that the core of the circadian clock consists of three proteins, KaiA, KaiB and KaiC (Ishiura et al., 1998), whose oscillating behavior can be reconstituted in vitro (Nakajima et al, 2005). Many studies have addressed the robustness of circadian rhythms to demographic noise in Kai proteins (Mihalcescu et al, 2004; Chabot et al, 2007; Teng et al, 2013; Pittayakanchit et al, 2018; Chew et al., 2018), but copy number variations in KaiC phosphoforms, which impact directly on clock function, has not been previously considered

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Conclusion