This strain is a derivative of MG1655 that contains and under control of a promoter, which were inserted into the chromosome at the and locus. concentration fluctuated at low amplitude with sinusoidal-like dependence on cell cycle phase. Traces of individual cells were consistent with a sudden two-fold increase in expression rate, together with other non-cell cycle noise. A model was used to relate the findings and to explain the cell cycle-induced variations for different chromosomal positions. Conclusions We found that the bacterial cell cycle contribution to expression noise consists of two parts: a deterministic oscillation in synchrony with the cell cycle and a stochastic CD40LG component caused by variable timing of gene replication. Together, they cause half of the expression rate noise. Concentration fluctuations are partially suppressed by a noise cancelling mechanism that involves the exponential growth of cellular volume. A model explains how the functional form of the concentration oscillations depends on chromosome position. Electronic supplementary material The online version of this article (doi:10.1186/s12915-016-0231-z) contains supplementary material, which is available to authorized users. have indeed shown quasi-periodic fluctuations of protein expression rates [20] and concentrations [21] in synchrony with the cell cycle. The prokaryotic cell cycle does not display such distinct replication and growth phases. cells as they grew into micro-colonies and measured gene expression as the fluorescence signal of chromosomally encoded fluorescent proteins (Additional file 1: movie S1). As shown herein, understanding the temporal dynamics requires detailed information on cellular volume increases in time, as protein concentrations are affected both by time-dependent expression and dilution. Thus, we accurately determined protein expression and cell size at sub-cell cycle resolution. We further developed a model to predict the cell cycle dependence and amplitude of these quasi-periodic fluctuations in expression rate and concentration. The model predicted their dependence on chromosomal position, which we LY-411575 tested with genetic constructs. Results and discussion The protein production rate fluctuates quasi-periodically To measure the effect of the cell cycle on protein expression, we first determined protein production rate as quantified by the time derivative of the total cellular fluorescence (Methods). Taking the data for all cells with a completed cell cycle (n?=?393) over all cell cycle phases, the protein expression rate displayed a total noise intensity (defined as standard deviation divided by the mean) of 0.48 [17]. When plotting the production rate versus cell cycle phase (where 0 is cell birth and 1 is cell division) and averaging over all cells (Fig.?1a), it displayed the following trend: it was approximately constant in the first half, after which it rose to about two-fold at the LY-411575 end of the cycle (Fig.?1b, Additional file 2: Figure S1). An initially constant rate and two-fold increase is consistent with the known chromosome replication pattern for the observed mean growth rate (0.6 dbl/h): a single chromosome copy in the first period of the cell cycle, after which replication occurs in the second period that makes two copies [29]. Each chromosome duplicate yields a set expression price then. This isn’t unreasonable, as additional components necessary for manifestation, such LY-411575 as for example RNA ribosomes and polymerases, two times through the entire cell routine also. At faster development, replication occurs through the entire cell routine for multiple nested chromosome copies [30]. Regularly, we LY-411575 discovered that the creation price had not been toned primarily, but instead increased continuously through the entire cell routine when growing on the different moderate that supported an increased mean development rate of just one 1.8 dbl/h (Additional file 2: Figure S2). The full total increase continued to be two-fold, in contract with an anticipated doubling of the real amount of gene copies. General, these data indicate how the mean protein manifestation rate is probable proportional towards the gene duplicate number and therefore doubles during chromosome replication. This variant is more constant at high development.