Fig. 4. A large fraction of E. coli genes are transcribed less than once per cell cycle.

(A) A comparison of simulation and experimental results (32) with regard to the number of proteins expressed per cell for each gene. The proteins are grouped as being highly abundant if the measured count per cell is greater than or equal to 30, and otherwise low-abundant. The R-squared statistic is computed separately for each group on the log-transformed data. (B) Simulations of mRNA and protein expression over multiple generations for genes that are expressed at high (left, in red) and low levels (right, in blue; note that colors are conserved to preserve meaning throughout the figure) of transcriptional frequencies. Counts are shown for a representative six-generation long window, with an arbitrarily chosen zeroth starting generation. (C) Frequency of observing at least one gene transcript per generation over a 32-generation simulation. Histograms show that 1,547 genes are transcribed at least once per cell cycle (red), 203 genes are essentially never expressed in this environment (yellow), and the remaining 2,603 genes are transcribed with a frequency between zero and one (blue). (D) Expression frequency analysis of known essential genes. (E) Division of the sub-generationally transcribed genes into those for which at least one protein is present at all times during the simulations, and those for which the protein is absent for at least one time step (gray bars). Protein products of essential genes are indicated by the blue bars. Distinct protein units represent sub-generationally expressed monomers and protein complexes composed of sub-generationally expressed monomers. (F) Transcription, translation, complexation and metabolic activity of the PabAB heterodimer, which catalyzes a reaction responsible for producing folates. Each new generation is indicated with a tick mark along the x-axis; the gray area highlights a period of time in which the heterodimer is not present in the cell. All y-axes are linearly scaled except the [10^-3, 0.44] region of the reaction flux plot which is log-scaled for better readability. Full details of the analysis required to generate this figure, as well as a pointer to the generating code, can be found in the Supplement, Section 1.2.