Noise Minimization in Eukaryotic Gene Expression

By Hunter B. Fraser, Aaron E. Hirsh, G. Giaever, J. Kumm, Michael B. Eisen. PLoS Biology, 2004

446 citations recorded by the source corpus.

All organisms have elaborate mechanisms to control rates of protein production. However, protein production is also subject to stochastic fluctuations, or “noise.” Several recent studies in Saccharomyces cerevisiae and Escherichia coli have investigated the relationship between transcription and translation rates and stochastic fluctuations in protein levels, or more generally, how such randomness is a function of intrinsic and extrinsic factors. However, the fundamental question of whether stochasticity in protein expression is generally biologically relevant has not been addressed, and it remains unknown whether random noise in the protein production rate of most genes significantly affects the fitness of any organism. We propose that organisms should be particularly sensitive to variation in the protein levels of two classes of genes: genes whose deletion is lethal to the organism and genes that encode subunits of multiprotein complexes. Using an experimentally verified model of stochastic gene expression in S. cerevisiae, we estimate the noise in protein production for nearly every yeast gene, and confirm our prediction that the production of essential and complex-forming proteins involves lower levels of noise than does the production of most other genes. Our results support the hypothesis that noise in gene expression is a biologically important variable, is generally detrimental to organismal fitness, and is subject to natural selection.

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/53c7de9b45f6305e78ceaff7c2a8ea201713c757

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Citations in the corpus

Analytical distributions for stochastic gene expression (2008, background): “Large fluctuations can vastly reduce the efficiency of complex assembly by preventing complete complexes forming because of a shortage of one or more components [11, 35].”
Robustness of Cellular Functions (2004, unknown): “Hence, the claim of higher order detrimental effects (Fraser et al., 2004) as well as for behavior to be robust and thereby to confer functional exploiting noise to generate beneficial diversity (Raser advantage requires careful justification. and O'Shea, 2004).”
Phenotypic consequences of promoter-mediated transcriptional noise. (2006, background): “Noise in gene expression can be viewed as a detriment to cell function necessitating minimization (Becskei and Serrano , 2000; Fraser et al., 2004; Acar et al., 2005), as fluctuations in protein levels may disrupt intracellular signaling and cellular regulation.”
Insights into the regulation of protein abundance from proteomic and transcriptomic analyses (2012, unknown): “In addition, translation regulation has a role in the lack of correlation: when comparing different classes of genes across yeast cells, concentrations of proteins in the same complex are less noisy compared with proteins that are not within one comple”
Histone variant H2A.Z marks the 5' ends of both active and inactive genes in euchromatin. (2005, methodology): “To address this issue, we selected from the H2A.Z ChIP microarray data those genes that contain two H2A.Z nucleosomes flanking a NFR and compared the levels of H2A.Z enrichment at each of the two nucleosomes to two distinct measurements of transcriptional activity for the corresponding gene (Figure ”
Noise in protein expression scales with natural protein abundance (2006, background): “For example, it has been hypothesized that essential genes and genes that work in a complex will be characterized by low noise level”