Figure 1.
Decomposing gene expression variability into extrinsic and intrinsic noise using a two-color reporter assay.
Two identical copies of a promoter express two different reporter proteins. Correlation in reporter levels is a measure of extrinsic noise that arises from cell-to-cell differences in shared cellular factors. Intrinsic noise is the protein variability that is not accounted for by extrinsic noise, and typically originates from the inherent stochastic nature of biochemical processes.
Figure 2.
Schematic of the gene expression model (left). The stochastic model consists of four events that occur randomly at exponentially-distributed time intervals. Discrete changes in the mRNA () and protein (
) population count for different events are shown in the second column of the table. Third column lists the event propensity function that determines how often an event occurs.
Figure 3.
Gene expression variability for individual-parameter fluctuations.
Intrinsic and extrinsic noise measured in two-color assay as a function of (extent of parameter fluctuations) for fluctuations in the transcription burst frequency (left), transcription burst size (middle) and mRNA translation rate (right). Intrinsic noise is independent of
for transcription burst frequency fluctuations. However, for transcription burst size or translation rate fluctuations, intrinsic noise increases with
. Extrinsic noise always increases with
and is the largest for translation rate fluctuations.
Figure 4.
Gene expression variability for multiple-parameter fluctuations.
Intrinsic noise measured in two-color assay as a function of (extent of parameter fluctuations) for simultaneous fluctuations in the transcription burst frequency/translation rate (left), and transcription burst size/translation rate (right). The latter case generates larger intrinsic noise and also yields different qualitative trends compared to burst frequency/translation rate fluctuations. Depending on parameter regimes, intrinsic noise can increase, decreases or change non-monotonically with
. High, medium, low protein populations correspond to an average of 300, 30 and 10 protein copies per cell, respectively. Other model parameters taken as mRNA half-life = 2 hours, protein half-life = time-scale of parameter fluctuations = 10 hours, mean transcriptional burst size = 10 and mean mRNA copy number per cell = 50.