A Minimalistic Resource Allocation Model to Explain Ubiquitous Increase in Protein Expression with Growth Rate

PLoS One. 2016 Apr 13;11(4):e0153344. doi: 10.1371/journal.pone.0153344. eCollection 2016.

Abstract

Most proteins show changes in level across growth conditions. Many of these changes seem to be coordinated with the specific growth rate rather than the growth environment or the protein function. Although cellular growth rates, gene expression levels and gene regulation have been at the center of biological research for decades, there are only a few models giving a base line prediction of the dependence of the proteome fraction occupied by a gene with the specific growth rate. We present a simple model that predicts a widely coordinated increase in the fraction of many proteins out of the proteome, proportionally with the growth rate. The model reveals how passive redistribution of resources, due to active regulation of only a few proteins, can have proteome wide effects that are quantitatively predictable. Our model provides a potential explanation for why and how such a coordinated response of a large fraction of the proteome to the specific growth rate arises under different environmental conditions. The simplicity of our model can also be useful by serving as a baseline null hypothesis in the search for active regulation. We exemplify the usage of the model by analyzing the relationship between growth rate and proteome composition for the model microorganism E.coli as reflected in recent proteomics data sets spanning various growth conditions. We find that the fraction out of the proteome of a large number of proteins, and from different cellular processes, increases proportionally with the growth rate. Notably, ribosomal proteins, which have been previously reported to increase in fraction with growth rate, are only a small part of this group of proteins. We suggest that, although the fractions of many proteins change with the growth rate, such changes may be partially driven by a global effect, not necessarily requiring specific cellular control mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Escherichia coli / growth & development
  • Escherichia coli / metabolism*
  • Models, Theoretical*
  • Protein Processing, Post-Translational
  • Proteome / metabolism*
  • Proteomics
  • Resource Allocation*
  • Ribosomes / metabolism

Substances

  • Proteome

Grants and funding

This work was supported by European Research Council, 646827 - NOVCARBFIX, (https://erc.europa.eu/, RM) and Alternative sustainable Energy Research Initiative, Alternative Sustainable Energy Research PhD fellowships program (http://www.weizmann.ac.il/AERI/, UB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.