Nature, nurture, or chance: stochastic gene expression and its consequences

Abstract

Gene expression is a fundamentally stochastic process, with randomness in transcription and translation leading to cell-to-cell variations in mRNA and protein levels. This variation appears in organisms ranging from microbes to metazoans, and its characteristics depend both on the biophysical parameters governing gene expression and on gene network structure. Stochastic gene expression has important consequences for cellular function, being beneficial in some contexts and harmful in others. These situations include the stress response, metabolism, development, the cell cycle, circadian rhythms, and aging.

Figure 1. Intrinsic and extrinsic contributions to noise in gene expression

A) A fluorescence image of individual E. coli displaying marked cell-to-cell variability in the expression of two identically regulated fluorescent proteins. B) Schematic depiction of the temporal behaviors of extrinsic noise (upper) and intrinsic noise (lower). C) Expected cell-to-cell variations when fluctuations are intrinsic, extrinsic or both. (A and B adapted from Elowitz et al., 2002).

Figure 2. Noise in prokaryotic gene expression depends on the rates of transcription and translation

A) When the transcription rate is high, variability in protein levels is low, but B) when the transcription rate is lowered and the translation rate is raised, gene expression is far noisier, even at the same mean, as shown in Ozbudak et al. (2002).

Figure 3. The Contribution of Transcriptional Bursts to Cell-to-Cell Variability

A) Transcription without bursts with a relatively small amount of noise. B) Bursts in transcription can cause significantly higher variability, even when producing the same mean number of transcripts. C) In situ detection of individual mRNA molecules reveals large cell-to-cell variability in mammalian cells. D) Experimental histogram of mRNA numbers. The grey dashed line depicts the theoretical distribution one would expect in the absence of transcriptional bursts. (C and D adapted from Raj et al., 2006)