Advantages and Disadvantages of Circadian Rhythms: A Tale of Two Microbes

Abstract

Circadian clocks generate reliable ~24‐h rhythms despite being based on stochastic biochemical reactions. The circadian clock in Synechococcus elongatus uses a post‐translational oscillator that cycles deterministically in a test tube. Because the volume of a single bacterial cell is much smaller than a macroscopic reaction, we asked how clocks in single cells function reliably. Here, we show that S. elongatus cells must express many thousands of copies of Kai proteins to effectively suppress timing errors. Stochastic modeling shows that this requirement stems from noise amplification in the post‐translational feedback loop that sustains oscillations. The much smaller cyanobacterium Prochlorococcus expresses only hundreds of Kai protein copies and has a simpler, hourglass‐like Kai system. These altered dynamics are likely due to the loss of the KaiA protein in the Prochlorococcus system, which acts as a key node for the negative feedback loop in the system. Using advanced sampling techniques and molecular dynamics simulations, we find that KaiA acts as a nucleotide exchange factor by destabilizing the hexameric structure of the C‐terminal domain of KaiC. In KaiA‐less versions of this system, nucleotide exchange is presumably constitutive, potentially allowing the KaiC hourglass to act by measuring the ATP/ADP ratio in the cell. We show that this hourglass strategy can outperform a free‐running clock if internal noise is significant. This conclusion has implications for clock evolution and synthetic oscillator design, and it suggests hourglass‐like behavior may be widespread in microbes.Support or Funding InformationThis work was supported by NIH training grant T32‐GM007281, NIH F30 fellowship F30‐GM117962 (to J.C.), NIH R01‐GM107369 and a Pew Biomedical Scholars award (to M.J.R.).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.