title: Mutation rate, spectrum, topology, and context-dependency in the DNA mismatch repair-deficient Pseudomonas fluorescens ATCC948.
abstract: High levels of genetic diversity exist among natural isolates of the bacterium Pseudomonas fluorescens, and are especially elevated around the replication terminus of the genome, where strain-specific genes are found. In an effort to understand the role of genetic variation in the evolution of Pseudomonas, we analyzed 31,106 base substitutions from 45 mutation accumulation lines of P. fluorescens ATCC948, naturally deficient for mismatch repair, yielding a base-substitution mutation rate of 2.34 × 10(-8) per site per generation (SE: 0.01 × 10(-8)) and a small-insertion-deletion mutation rate of 1.65 × 10(-9) per site per generation (SE: 0.03 × 10(-9)). We find that the spectrum of mutations in prophage regions, which often contain virulence factors and antibiotic resistance, is highly similar to that in the intergenic regions of the host genome. Our results show that the mutation rate varies around the chromosome, with the lowest mutation rate found near the origin of replication. Consistent with observations from other studies, we find that site-specific mutation rates are heavily influenced by the immediately flanking nucleotides, indicating that mutations are context dependent.
authors.affiliation: Department of Biology, Indiana University, Bloomington longhongan@gmail.com.
authors.forename: Hongan
authors.initials: H
authors.lastname: Long
authors.affiliation: Department of Biology, Indiana University, Bloomington.
authors.forename: Way
authors.initials: W
authors.lastname: Sung
authors.affiliation: Department of Biology, Indiana University, Bloomington.
authors.forename: Samuel F
authors.initials: SF
authors.lastname: Miller
authors.affiliation: Department of Biology, Indiana University, Bloomington.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Ackerman
authors.affiliation: Department of Biology, Indiana University, Bloomington National Center for Genome Analysis Support, Indiana University, Bloomington.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Doak
authors.affiliation: Department of Biology, Indiana University, Bloomington.
authors.forename: Michael
authors.initials: M
authors.lastname: Lynch
mesh_terms: D053843:DNA Mismatch Repair / Q000235:genetics*; D004261:DNA Replication / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics; D014644:Genetic Variation; D054884:Host-Pathogen Interactions / Q000235:genetics*; D006801:Humans; D054643:INDEL Mutation / Q000235:genetics; D059645:Mutation Rate; D011551:Pseudomonas fluorescens / Q000235:genetics
keywords: mutation hotspots; neutral evolution; nonrandom mutations; phage evolution