Asymmetric Context-Dependent Mutation Patterns Revealed through Mutation-Accumulation Experiments.
Despite the general assumption that site-specific mutation rates are independent of the local sequence context, a growing body of evidence suggests otherwise. To further examine context-dependent patterns of mutation, we amassed 5,645 spontaneous mutations in wild- type (WT) and mismatch-repair deficient (MMR(-)) mutation-accumulation (MA) lines of the gram-positive model organism Bacillus subtilis. We then analyzed>7,500 spontaneous base-substitution mutations across B. subtilis, Escherichia coli, and Mesoplasma florum WT and MMR(-) MA lines, finding a context-dependent mutation pattern that is asymmetric around the origin of replication. Different neighboring nucleotides can alter site-specific mutation rates by as much as 75-fold, with sites neighboring G:C base pairs or dimers involving alternating pyrimidine-purine and purine-pyrimidine nucleotides having significantly elevated mutation rates. The influence of context-dependent mutation on genome architecture is strongest in M. florum, consistent with the reduced efficiency of selection in organisms with low effective population size. If not properly accounted for, the disparities arising from patterns of context-dependent mutation can significantly influence interpretations of positive and purifying selection.
Department of Biology, Indiana University, Bloomington waysung@indiana.edu.
Way
W
Sung
Department of Biology, Indiana University, Bloomington.
Matthew S
MS
Ackerman
Department of Biology, Indiana University, Bloomington.
Jean-François
JF
Gout
Department of Biology, Indiana University, Bloomington.
Samuel F
SF
Miller
Department of Biology, Indiana University, Bloomington.
Emily
E
Williams
Department of Biology, Indiana University, Bloomington.
Patricia L
PL
Foster
Department of Biology, Indiana University, Bloomington.
Michael
M
Lynch
D001412:Bacillus subtilis / Q000235:genetics; D001419:Bacteria / Q000235:genetics*; D053843:DNA Mismatch Repair / Q000235:genetics*; D045622:Entomoplasmataceae / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics; D016680:Genome, Bacterial; D000067552:Mutation Accumulation; D059645:Mutation Rate; D009711:Nucleotides / Q000235:genetics
D009711:Nucleotides
Bacillus subtilis; context-dependent mutation; mismatch repair; mutation rate