Journal
PLOS COMPUTATIONAL BIOLOGY
Volume 8, Issue 12, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pcbi.1002846
Keywords
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Funding
- Marie-Curie Actions
- ERC
- ERASysBio+ ERANET
- MICINN [BFU2008-00365, BFU201126206]
- AGAUR
- EMBO Young Investigator Program
- EU [277899 4DCellFate]
- EMBL-CRG Systems Biology Program
- ICREA Funding Source: Custom
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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.
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