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Noise in protein expression scales with natural protein abundance

Nature Genetics volume 38, pages 636–643 (2006)Cite this article

Abstract

Noise in gene expression is generated at multiple levels, such as transcription and translation, chromatin remodeling and pathway-specific regulation. Studies of individual promoters have suggested different dominating noise sources, raising the question of whether a general trend exists across a large number of genes and conditions. We examined the variation in the expression levels of 43 Saccharomyces cerevisiae proteins, in cells grown under 11 experimental conditions. For all classes of genes and under all conditions, the expression variance was approximately proportional to the mean; the same scaling was observed at steady state and during the transient responses to the perturbations. Theoretical analysis suggests that this scaling behavior reflects variability in mRNA copy number, resulting from random 'birth and death' of mRNA molecules or from promoter fluctuations. Deviation of coexpressed genes from this general trend, including high noise in stress-related genes and low noise in proteasomal genes, may indicate fluctuations in pathway-specific regulators or a differential activation pattern of the underlying gene promoters.

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Figure 1: Single-cell distributions of fluorescence levels.
Figure 2: Scaling of noise with mean protein abundance.
Figure 3: Theoretical analysis of noise propagation.
Figure 4: Noise pattern of PRE9.
Figure 5: Transient response to perturbations.
Figure 6: Noise residuals.

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Acknowledgements

We thank the members of the Barkai and Pilpel labs for discussions and help in the experiments. This work was supported by the Tauber fund through the Foundations of Cognition Initiative. N.B. acknowledges the hospitality of the Bauer Center at Harvard, where part of this research was performed. Y.P. is an incumbent of the Aser Rothstein Career Development chair in Genetic Diseases. Y.P. acknowledges financial support from EMBRACE (a European Model for Bioinformatics Research and Community Education), funded by the European Commission within its FP6 Program.

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Authors and Affiliations

  1. Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, 76100, Israel

    Arren Bar-Even, Miri Carmi, Yitzhak Pilpel & Naama Barkai

  2. Department of Systems Biology, Harvard University, Boston, 02115, Massachusetts, USA

    Johan Paulsson

  3. Department of Applied Mathematics and Theoretical Physics, University of Cambridge, Cambridge, CB3 0WA, UK

    Johan Paulsson

  4. Department of Molecular and Cellular Biology, Howard Hughes Medical Institute, Harvard University, 7 Divinity Avenue, Cambridge, 02138, Massachusetts, USA

    Narendra Maheshri & Erin O'Shea

  5. Physics of Complex Systems, Weizmann Institute of Science, Rehovot, 76100, Israel

    Naama Barkai

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  1. Arren Bar-Even
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Correspondence to Yitzhak Pilpel or Naama Barkai.

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Supplementary information

Supplementary Fig. 1

Dual reporter assay. (PDF 414 kb)

Supplementary Fig. 2

Doubling time effect. (PDF 16 kb)

Supplementary Fig. 3

Correlation between protein abundance and fluorescence. (PDF 4 kb)

Supplementary Fig. 4

mRNA data set comparison. (PDF 6 kb)

Supplementary Figure 5

GFP-fused versus promoter-GFP. (PDF 6 kb)

Supplementary Fig. 6

Normal and log-normal patterns. (PDF 9 kb)

Supplementary Methods (PDF 73 kb)

Supplementary Note (PDF 81 kb)

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Bar-Even, A., Paulsson, J., Maheshri, N. et al. Noise in protein expression scales with natural protein abundance. Nat Genet 38, 636–643 (2006). https://doi.org/10.1038/ng1807

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