Expression noise facilitates the evolution of gene regulation.

Luise Wolf,Erik Van Nimwegen,Olin K Silander

doi:10.7554/elife.05856

Luise Wolf, Erik Van Nimwegen + Show 1 more

Open Access

https://doi.org/10.7554/elife.05856

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Journal: eLife	Publication Date: Jun 17, 2015
Citations: 100	License type: CC BY 4.0

Affiliation: University of Basel, SIB Swiss Institute of Bioinformatics

Abstract

Although it is often tacitly assumed that gene regulatory interactions are finely tuned, how accurate gene regulation could evolve from a state without regulation is unclear. Moreover, gene expression noise would seem to impede the evolution of accurate gene regulation, and previous investigations have provided circumstantial evidence that natural selection has acted to lower noise levels. By evolving synthetic Escherichia coli promoters de novo, we here show that, contrary to expectations, promoters exhibit low noise by default. Instead, selection must have acted to increase the noise levels of highly regulated E. coli promoters. We present a general theory of the interplay between gene expression noise and gene regulation that explains these observations. The theory shows that propagation of expression noise from regulators to their targets is not an unwanted side-effect of regulation, but rather acts as a rudimentary form of regulation that facilitates the evolution of more accurate regulation.

Highlights

Many studies over the last decade have established that, even within homogeneous environments, gene expression varies across genetically identical cells due to thermodynamic fluctuations in the molecular events underlying gene expression and the small numbers of molecules involved (Elowitz et al, 2002; Rao et al, 2002)
In order to assess how natural selection has acted on the transcriptional noise of promoters, it is critical to determine what default noise levels would be exhibited by promoters that have not been selected for their noise properties
We have shown that, by comparing naturally observed variation in a particular trait with variation observed in synthetic systems that were evolved under well-controlled selective conditions, definite inferences can be made about the selection pressures that have acted on the natural systems

Summary

Introduction

Many studies over the last decade have established that, even within homogeneous environments, gene expression varies across genetically identical cells due to thermodynamic fluctuations in the molecular events underlying gene expression and the small numbers of molecules involved (Elowitz et al, 2002; Rao et al, 2002). Basic thermodynamic fluctuations and Brownian motion of the molecular players would cause transcription initiation at a given promoter to occur with a constant probability per unit time, and the corresponding mRNAs to decay with a constant probability per unit time, leading to a Poissonian steady-state distribution in the number of transcripts. Such Poissonian fluctuations are observed for some genes, most genes exhibit much larger fluctuations in their mRNA copy number. Appendix 1—figure 6 shows the reverse cumulative distributions of observed intensities in these control populations (colored lines)

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