Asymmetric Context-Dependent Mutation Patterns Revealed Through Mutation-Accumulation Experiments

Overview

Journal Mol Biol Evol

Publisher Oxford University Press

Specialty Biology

Date 2015 Mar 10

PMID 25750180

Citations 83

Authors

Way Sung

Matthew S Ackerman

Jean-Francois Gout

Samuel F Miller

Emily Williams

Patricia L Foster

Michael Lynch

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

The mutational landscape of Bacillus subtilis conditional hypermutators shows how proofreading skews DNA polymerase error rates.

Tanneur I, Dervyn E, Guerin C, Kon Kam King G, Jules M, Nicolas P Nucleic Acids Res. 2025; 53(5).

PMID: 40057377 PMC: 11890065. DOI: 10.1093/nar/gkaf147.

Harnessing microbial heterogeneity for improved biosynthesis fueled by synthetic biology.

Cao Y, Li J, Liu L, Du G, Liu Y Synth Syst Biotechnol. 2024; 10(1):281-293.

PMID: 39686977 PMC: 11646789. DOI: 10.1016/j.synbio.2024.11.004.

The Effect of the Presence and Absence of DNA Repair Genes on the Rate and Pattern of Mutation in Bacteria.

Kalogiannis G, Eyre-Walker A Genome Biol Evol. 2024; 16(10).

PMID: 39376054 PMC: 11493085. DOI: 10.1093/gbe/evae216.

Spontaneous mutations and mutational responses to penicillin treatment in the bacterial pathogen D39.

Jiang W, Lin T, Pan J, Rivera C, Tincher C, Wang Y Mar Life Sci Technol. 2024; 6(2):198-211.

PMID: 38827133 PMC: 11136922. DOI: 10.1007/s42995-024-00220-6.

Clinical, Neuroimaging, and Metabolic Footprint of the Neurodevelopmental Disorder Caused by Monoallelic Variants.

Wortmann S, Feichtinger R, Abela L, van Gemert L, Aubart M, Dufeu-Berat C Neurol Genet. 2024; 10(2):e200146.

PMID: 38617198 PMC: 11010246. DOI: 10.1212/NXG.0000000000200146.

References

KOCH R . The influence of neighboring base pairs upon base-pair substitution mutation rates. Proc Natl Acad Sci U S A. 1971; 68(4):773-6. PMC: 389040. DOI: 10.1073/pnas.68.4.773. View

Kibota T, Lynch M . Estimate of the genomic mutation rate deleterious to overall fitness in E. coli. Nature. 1996; 381(6584):694-6. DOI: 10.1038/381694a0. View

Sung W, Tucker A, Doak T, Choi E, Thomas W, Lynch M . Extraordinary genome stability in the ciliate Paramecium tetraurelia. Proc Natl Acad Sci U S A. 2012; 109(47):19339-44. PMC: 3511141. DOI: 10.1073/pnas.1210663109. View

McLean M, Wolfe K, Devine K . Base composition skews, replication orientation, and gene orientation in 12 prokaryote genomes. J Mol Evol. 1998; 47(6):691-6. DOI: 10.1007/pl00006428. View

Powdel B, Borah M, Ray S . Strand-specific mutational bias influences codon usage of weakly expressed genes in Escherichia coli. Genes Cells. 2010; 15(7):773-82. DOI: 10.1111/j.1365-2443.2010.01417.x. View

Duret L . Mutation patterns in the human genome: more variable than expected. PLoS Biol. 2009; 7(2):e1000028. PMC: 2634789. DOI: 10.1371/journal.pbio.1000028. View

Tillier E, Collins R . The contributions of replication orientation, gene direction, and signal sequences to base-composition asymmetries in bacterial genomes. J Mol Evol. 2001; 50(3):249-57. DOI: 10.1007/s002399910029. View

Dreiseikelmann B, Wackernagel W . Absence in Bacillus subtilis and Staphylococcus aureus of the sequence-specific deoxyribonucleic acid methylation that is conferred in Escherichia coli K-12 by the dam and dcm enzymes. J Bacteriol. 1981; 147(1):259-61. PMC: 216033. DOI: 10.1128/jb.147.1.259-261.1981. View

Sung W, Ackerman M, Miller S, Doak T, Lynch M . Drift-barrier hypothesis and mutation-rate evolution. Proc Natl Acad Sci U S A. 2012; 109(45):18488-92. PMC: 3494944. DOI: 10.1073/pnas.1216223109. View

10.

Yakovchuk P, Protozanova E, Frank-Kamenetskii M . Base-stacking and base-pairing contributions into thermal stability of the DNA double helix. Nucleic Acids Res. 2006; 34(2):564-74. PMC: 1360284. DOI: 10.1093/nar/gkj454. View

11.

Marin A, Xia X . GC skew in protein-coding genes between the leading and lagging strands in bacterial genomes: new substitution models incorporating strand bias. J Theor Biol. 2008; 253(3):508-13. DOI: 10.1016/j.jtbi.2008.04.004. View

12.

Beletskii A, Bhagwat A . Transcription-induced mutations: increase in C to T mutations in the nontranscribed strand during transcription in Escherichia coli. Proc Natl Acad Sci U S A. 1996; 93(24):13919-24. PMC: 19468. DOI: 10.1073/pnas.93.24.13919. View

13.

Yang , Bielawski . Statistical methods for detecting molecular adaptation. Trends Ecol Evol. 2000; 15(12):496-503. PMC: 7134603. DOI: 10.1016/s0169-5347(00)01994-7. View

14.

Haag-Liautard C, Coffey N, Houle D, Lynch M, Charlesworth B, Keightley P . Direct estimation of the mitochondrial DNA mutation rate in Drosophila melanogaster. PLoS Biol. 2008; 6(8):e204. PMC: 2517619. DOI: 10.1371/journal.pbio.0060204. View

15.

Sedgwick B . Repairing DNA-methylation damage. Nat Rev Mol Cell Biol. 2004; 5(2):148-57. DOI: 10.1038/nrm1312. View

16.

Hershberg R, Petrov D . Selection on codon bias. Annu Rev Genet. 2008; 42:287-99. DOI: 10.1146/annurev.genet.42.110807.091442. View

17.

Baele G, Van de Peer Y, Vansteelandt S . Modelling the ancestral sequence distribution and model frequencies in context-dependent models for primate non-coding sequences. BMC Evol Biol. 2010; 10:244. PMC: 2928787. DOI: 10.1186/1471-2148-10-244. View

18.

Hawk J, Stefanovic L, Boyer J, Petes T, Farber R . Variation in efficiency of DNA mismatch repair at different sites in the yeast genome. Proc Natl Acad Sci U S A. 2005; 102(24):8639-43. PMC: 1150857. DOI: 10.1073/pnas.0503415102. View

19.

Krzywinski M, Schein J, Birol I, Connors J, Gascoyne R, Horsman D . Circos: an information aesthetic for comparative genomics. Genome Res. 2009; 19(9):1639-45. PMC: 2752132. DOI: 10.1101/gr.092759.109. View

20.

Bulmer M . The selection-mutation-drift theory of synonymous codon usage. Genetics. 1991; 129(3):897-907. PMC: 1204756. DOI: 10.1093/genetics/129.3.897. View