PMID- 25539726 OWN - NLM STAT- MEDLINE DCOM- 20150916 LR - 20181113 IS - 1759-6653 (Electronic) IS - 1759-6653 (Linking) VI - 7 IP - 1 DP - 2014 Dec 23 TI - Mutation rate, spectrum, topology, and context-dependency in the DNA mismatch repair-deficient Pseudomonas fluorescens ATCC948. PG - 262-71 LID - 10.1093/gbe/evu284 [doi] AB - 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 x 10(-8) per site per generation (SE: 0.01 x 10(-8)) and a small-insertion-deletion mutation rate of 1.65 x 10(-9) per site per generation (SE: 0.03 x 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. CI - (c) The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. FAU - Long, Hongan AU - Long H AD - Department of Biology, Indiana University, Bloomington longhongan@gmail.com. FAU - Sung, Way AU - Sung W AD - Department of Biology, Indiana University, Bloomington. FAU - Miller, Samuel F AU - Miller SF AD - Department of Biology, Indiana University, Bloomington. FAU - Ackerman, Matthew S AU - Ackerman MS AD - Department of Biology, Indiana University, Bloomington. FAU - Doak, Thomas G AU - Doak TG AD - Department of Biology, Indiana University, Bloomington National Center for Genome Analysis Support, Indiana University, Bloomington. FAU - Lynch, Michael AU - Lynch M AD - Department of Biology, Indiana University, Bloomington. LA - eng SI - BioProject/PRJNA264995 GR - R01 GM036827/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20141223 PL - England TA - Genome Biol Evol JT - Genome biology and evolution JID - 101509707 SB - IM MH - DNA Mismatch Repair/*genetics MH - DNA Replication/genetics MH - Drug Resistance, Bacterial/genetics MH - *Genetic Variation MH - Host-Pathogen Interactions/*genetics MH - Humans MH - INDEL Mutation/genetics MH - *Mutation Rate MH - Pseudomonas fluorescens/genetics PMC - PMC4316635 OTO - NOTNLM OT - mutation hotspots OT - neutral evolution OT - nonrandom mutations OT - phage evolution EDAT- 2014/12/30 06:00 MHDA- 2015/09/17 06:00 PMCR- 2014/12/23 CRDT- 2014/12/26 06:00 PHST- 2014/12/26 06:00 [entrez] PHST- 2014/12/30 06:00 [pubmed] PHST- 2015/09/17 06:00 [medline] PHST- 2014/12/23 00:00 [pmc-release] AID - evu284 [pii] AID - 10.1093/gbe/evu284 [doi] PST - epublish SO - Genome Biol Evol. 2014 Dec 23;7(1):262-71. doi: 10.1093/gbe/evu284.