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The rate of the molecular clock and the cost of gratuitous protein synthesis

Germán Plata12, Max E Gottesman34 and Dennis Vitkup15*

Author Affiliations

1 Center for Computational Biology and Bioinformatics, Columbia University, 1130 St Nicholas Ave, New York City, NY 10032, USA

2 Integrated Program in Cellular, Molecular, Structural, and Genetic Studies, Columbia University, 1130 St Nicholas Ave, New York City, NY 10032, USA

3 Department of Microbiology and Immunology, Columbia University, 701 W. 168 St, New York City, NY 10032, USA

4 Department of Biochemistry and Molecular Biophysics, Columbia University, 701 W. 168 St, New York City, NY 10032, USA

5 Department of Biomedical Informatics, Columbia University, 1130 St Nicholas Ave, New York City, NY 10032, USA

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Genome Biology 2010, 11:R98  doi:10.1186/gb-2010-11-9-r98

Published: 29 September 2010

Abstract

Background

The nature of the protein molecular clock, the protein-specific rate of amino acid substitutions, is among the central questions of molecular evolution. Protein expression level is the dominant determinant of the clock rate in a number of organisms. It has been suggested that highly expressed proteins evolve slowly in all species mainly to maintain robustness to translation errors that generate toxic misfolded proteins. Here we investigate this hypothesis experimentally by comparing the growth rate of Escherichia coli expressing wild type and misfolding-prone variants of the LacZ protein.

Results

We show that the cost of toxic protein misfolding is small compared to other costs associated with protein synthesis. Complementary computational analyses demonstrate that there is also a relatively weaker, but statistically significant, selection for increasing solubility and polarity in highly expressed E. coli proteins.

Conclusions

Although we cannot rule out the possibility that selection against misfolding toxicity significantly affects the protein clock in species other than E. coli, our results suggest that it is unlikely to be the dominant and universal factor determining the clock rate in all organisms. We find that in this bacterium other costs associated with protein synthesis are likely to play an important role. Interestingly, our experiments also suggest significant costs associated with volume effects, such as jamming of the cellular environment with unnecessary proteins.