title: 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.
authors.affiliation: Bioinformatics and Genomics Program, Centre for Genomic Regulation (CRG), Barcelona, Spain. Tobias.Warnecke@crg.es
authors.forename: Tobias
authors.initials: T
authors.lastname: Warnecke
authors.forename: Fran
authors.initials: F
authors.lastname: Supek
authors.forename: Ben
authors.initials: B
authors.lastname: Lehner
mesh_terms: D004260:DNA Repair; D004926:Escherichia coli / Q000235:genetics* / Q000254:growth & development; D029968:Escherichia coli Proteins / Q000378:metabolism / Q000502:physiology*; D019143:Evolution, Molecular; D009154:Mutation; D010802:Phylogeny; D011485:Protein Binding
chemical_list: D029968:Escherichia coli Proteins