Fig. 4From: Evolution of the repression mechanisms in circadian clocksNovel “phospholock” model of the eukaryotic circadian clock. A Schematic of the “phospholock” model of the eukaryotic circadian clock. The activator complex, A, promotes transcription of the repressor gene, which is then translated to the repressor protein r. Next, the repressor protein(s) form complexes with other proteins, specifically kinases. Then, the repressor complex binds to the activator complex. Over time, the repressor proteins become gradually more phosphorylated until it dissociates, leaving the activator complex free, and thus completing the cycle. B The repression function f(R) (top) from System (E) and the sensitivity (bottom) for a specific parameter set (see the “Methods” section) with Kd=1. The ratio of phosphorylation to dephosphorylation is increased from 1 (blue) to 10000 (red). As the ratio increases, the cusp of the repression function sharpens, reflected in the increase in the magnitude of the peak sensitivity (bottom). C The percent of parameter sets that exhibit oscillations increases with increasing phosphorylation strength and varying Kd values (0.0001, 0.001, 0.01, 0.1, and 1). When the Kd values are small (≤ 0.01), the system is more likely to generate oscillations when dephosphorylation is stronger than phosphorylation. However, at more likely Kd levels, i.e., Kd≥0.1, the system is more likely to generate oscillations when phosphorylation is stronger than dephosphorylation. D Schematic of the phospholock mechanism with the additional phosphorylation of the activator (as in the Neurospora system). E The distribution of stoichiometric ratios (R:A) calculated from parameter sets that generate oscillations for increasing k3 values. Adding phosphorylation of the activator increases the range of stoichiometric ratios from parameter sets that exhibit oscillations as the k3 parameter increasesBack to article page