Nucleoid-Associated Proteins Affect Mutation Dynamics in E. coli in a Growth Phase-Specific Manner

Abstract

The binding of proteins can shield DNA from mutagenic processes but also interfere with efficient repair. How the presence of DNA-binding proteins shapes intra-genomic differences in mutability and, ultimately, sequence variation in natural populations, however, remains poorly understood. In this study, we examine sequence evolution in Escherichia coli in relation to the binding of four abundant nucleoid-associated proteins: Fis, H-NS, IhfA, and IhfB. We find that, for a subset of mutations, protein occupancy is associated with both increased and decreased mutability in the underlying sequence depending on when the protein is bound during the bacterial growth cycle. On average, protein-bound DNA exhibits reduced mutability compared to protein-free DNA. However, this net protective effect is weak and can be abolished or even reversed during stages of colony growth where binding coincides - and hence likely interferes with - DNA repair activity. We suggest that the four nucleoid-associated proteins analyzed here have played a minor but significant role in patterning extant sequence variation in E. coli.

DOI: 10.1371/journal.pcbi.1002846

Extracted Key Phrases

3 Figures and Tables

05010020132014201520162017
Citations per Year

68 Citations

Semantic Scholar estimates that this publication has 68 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@inproceedings{Warnecke2012NucleoidAssociatedPA, title={Nucleoid-Associated Proteins Affect Mutation Dynamics in E. coli in a Growth Phase-Specific Manner}, author={Tobias Warnecke and Fran Supek and Ben Lehner}, booktitle={PLoS Computational Biology}, year={2012} }