title: On the mutational topology of the bacterial genome.
abstract: By sequencing the genomes of 34 mutation accumulation lines of a mismatch-repair defective strain of Escherichia coli that had undergone a total of 12,750 generations, we identified 1625 spontaneous base-pair substitutions spread across the E. coli genome. These mutations are not distributed at random but, instead, fall into a wave-like spatial pattern that is repeated almost exactly in mirror image in the two separately replicated halves of the bacterial chromosome. The pattern is correlated to genomic features, with mutation densities greatest in regions predicted to have high superhelicity. Superimposed upon this pattern are regional hotspots, some of which are located where replication forks may collide or be blocked. These results suggest that, as they traverse the chromosome, the two replication forks encounter parallel structural features that change the fidelity of DNA replication.
authors: Department of Biology, Indiana University, Bloomington, Indiana 47405, USA. plfoster@indiana.edu
authors: Patricia L
authors: PL
authors: Foster
authors: Andrew J
authors: AJ
authors: Hanson
authors: Heewook
authors: H
authors: Lee
authors: Ellen M
authors: EM
authors: Popodi
authors: Haixu
authors: H
authors: Tang
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics; D002876:Chromosomes, Bacterial / Q000235:genetics; D004252:DNA Mutational Analysis; D004261:DNA Replication; D004269:DNA, Bacterial / Q000032:analysis* / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics; D029968:Escherichia coli Proteins / Q000235:genetics; D016680:Genome, Bacterial; D016014:Linear Models; D008957:Models, Genetic; D000070956:MutL Proteins; D009154:Mutation; D059645:Mutation Rate; D018741:Replication Origin
chemical_list: D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; C074770:MutL protein, E coli; D000251:Adenosine Triphosphatases; D000070956:MutL Proteins
keywords: DNA polymerase errors; chromosome structure; evolution; mutation rate; replication fidelity