Estimating mutation rates in low-replication experiments
Open accessAbstract
Since mutation rate is a key biological parameter, its proper estimation has received great attention for decades. However, instead of the mutation rate, many authors opt for reporting the average mutant frequency, a less meaningful quantity. This is because the standard methods to estimate the mutation rate, derived from the Luria and Delbrück's fluctuation analysis, ideally require high-replication experiments to be applied; a requirement often unattainable due to constraints of time, budget or sample availability. But the main problem with mutant frequency, apart from being less informative, is its poor reproducibility; an especially marked defect when the chosen average is the arithmetic mean. Several authors tried to avoid this by employing other averages (such as the median or the geometric mean) or discarding outliers, though as far as we know nobody has evaluated which method performs best under low-replication settings. Here we use computer simulations to compare the performance of different methods used in low-replication experiments (≤4 cultures). Besides the customary averages of mutant frequency, we also tested two well-known fluctuation methods. Contrary to common practice, our results support that fluctuation methods should be applied in such circumstances, as they perform as well as or better than any average of mutant frequency. In particular, experimentalists will benefit from using MSS maximum likelihood in low-replication experiments because it: (i) provid…
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A solution for the case ε ≠ 1 has been found by Stewart and reiterated by Jones.
“Solution for the case ε ≠ 1 has been found by Stewart and reiterated by Jones [9,31]:”
From Efficient, robust, and versatile fluctuation data analysis using MLE MUtation Rate calculator (mlemur) (2023) · cites this paper as [9]
Cites
R: A Language and Environment for Statistical Computing
R Core Team (2000) · doi:10.32614/r.manuals · Cited by 355,706 · see citing works
Mutations of bacteria from virus sensitivity to virus resistance
Luria, S. E., & Delbrück, M. (1943) · Genetics · doi:10.1093/genetics/28.6.491 · Cited by 3,894 · see citing works
The distribution of the numbers of mutants in bacterial populations
Lea, D. E., & Coulson, C. A. (1949) · Journal of Genetics · doi:10.1007/bf02986080 · Cited by 1,450 · see citing works
A constant rate of spontaneous mutation in DNA-based microbes.
Drake, J. W. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.16.7160 · Cited by 1,199 · see citing works
Experiments with the Chemostat on Spontaneous Mutations of Bacteria
Novick, A., & Szilard, L. (1950) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.36.12.708 · Cited by 725 · see citing works
Determining Mutation Rates in Bacterial Populations
Rosche, W. A., & Foster, P. L. (2000) · Methods · doi:10.1006/meth.1999.0901 · Cited by 482 · see citing works
Hall, B. M., Ma, C.-X., Liang, P., & Singh, K. K. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp253 · Cited by 375 · see citing works
Estimating the Per-Base-Pair Mutation Rate in the Yeast <i>Saccharomyces cerevisiae</i>
Lang, G. I., & Murray, A. W. (2008) · Genetics · doi:10.1534/genetics.107.071506 · Cited by 344 · see citing works
Methods for determining spontaneous mutation rates
Foster, P. L. (2006) · Methods in Enzymology · doi:10.1016/s0076-6879(05)09012-9 · Cited by 302 · see citing works
Ciofu, O., Mandsberg, L. F., Bjarnsholt, T., Wassermann, T., & Høiby, N. (2009) · Microbiology · doi:10.1099/mic.0.033993-0 · Cited by 195 · see citing works
Sarkar, S., Ma, W. T., & Sandri, G. V. H. (1992) · Genetica · doi:10.1007/bf00120324 · Cited by 181 · see citing works
Progress of a half century in the study of the Luria-Delbrück distribution
Zheng, Q. (1999) · Mathematical Biosciences · doi:10.1016/s0025-5564(99)00045-0 · Cited by 144 · see citing works
Stewart, F. M., Gordon, D. M., & Levin, B. R. (1990) · Genetics · doi:10.1093/genetics/124.1.175 · Cited by 126 · see citing works
Role of Mutation in Pseudomonas aeruginosa Biofilm Development
Conibear, T. C. R., Collins, S., & Webb, J. S. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006289 · Cited by 121 · see citing works
Luria-Delbrück fluctuation experiments: design and analysis.
Jones, M. E., Thomas, S. M., & Rogers, A. (1994) · Genetics · doi:10.1093/genetics/136.3.1209 · Cited by 96 · see citing works
A Practical Guide to Measuring Mutation Rates in Antibiotic Resistance
Pope, C., O'Sullivan, D., McHugh, T. D., & Gillespie, S. (2008) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01152-07 · Cited by 96 · see citing works
Pitfalls and practice of Luria-Delbrück fluctuation analysis: a review.
Kendal, W. S., & Frost, P. (1988) · PubMed · Cited by 92 · see citing works
Hypermutable bacteria isolated from humans – a critical analysis
Hall, L. M. C., & Henderson-Begg, S. K. (2006) · Microbiology · doi:10.1099/mic.0.29079-0 · Cited by 86 · see citing works
Mutation and growth rates from Luria-Delbrück fluctuation tests.
Koch, A. L. (1982) · Mutation Research · doi:10.1016/0027-5107(82)90252-4 · Cited by 81 · see citing works
Fluctuation tests: how reliable are the estimates of mutation rates?
Stewart, F. M. (1994) · Genetics · doi:10.1093/genetics/137.4.1139 · Cited by 78 · see citing works
Statistical and algorithmic methods for fluctuation analysis with SALVADOR as an implementation
Zheng, Q. (2002) · Mathematical Biosciences · doi:10.1016/s0025-5564(02)00087-1 · Cited by 70 · see citing works
Kenna, D., Doherty, C. J., Foweraker, J. E., Macaskill, L., Barcus, V. A., & Govan, J. R. W. (2007) · Microbiology · doi:10.1099/mic.0.2006/005082-0 · Cited by 63 · see citing works
Modeling and measurement of the spontaneous mutation rate in mammalian cells
Rossman, T. G., Goncharova, E. I., & Nadas, A. J. (1995) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/0027-5107(94)00190-g · Cited by 49 · see citing works
Bayesian Procedures for the Estimation of Mutation Rates from Fluctuation Experiments
Asteris, G., & Sarkar, S. (1996) · Genetics · doi:10.1093/genetics/142.1.313 · Cited by 46 · see citing works
The GO system prevents ROS-induced mutagenesis and killing inPseudomonas aeruginosa
Sanders, L. H., Sudhakaran, J., & Sutton, M. D. (2009) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.2009.01550.x · Cited by 37 · see citing works
Development of Escherichia coli rifaximin-resistant mutants: frequency of selection and stability
Ruiz, J., Mensa, L., Pons, M. J., Vilà, J., & Gascón, J. (2008) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkn078 · Cited by 31 · see citing works
A Simple Formula for Obtaining Markedly Improved Mutation Rate Estimates
Gerrish, P. (2008) · Genetics · doi:10.1534/genetics.108.091777 · Cited by 28 · see citing works
A robust estimator of mutation rates
Wu, X., Strome, E. D., Meng, Q., Hastings, P. J., Plon, S. E., & Kimmel, M. (2008) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2008.11.015 · Cited by 22 · see citing works
Foster, P. L. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.14.7617 · Cited by 17 · see citing works
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MacLean, R. C., Barceló, C. T., & Moxon, R. E. (2013) · Nature Reviews Genetics · doi:10.1038/nrg3415 · Cited by 144 · see citing works
The Escherichia coli SOS Gene dinF Protects against Oxidative Stress and Bile Salts
Rodríguez-Beltrán, J., Rodríguez-Rojas, A., Guelfo, J. R., Couce, A., & Blázquez, J. (2012) · PLoS ONE · doi:10.1371/journal.pone.0034791 · Cited by 44 · see citing works
Self-citationCationic Peptides Facilitate Iron-induced Mutagenesis in Bacteria
Rodríguez-Rojas, A., Makarova, O., Müller, U., & Rolff, J. (2015) · PLoS Genetics · doi:10.1371/journal.pgen.1005546 · Cited by 34 · see citing works
A new practical guide to the Luria–Delbrück protocol
Zheng, Q. (2015) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2015.08.005 · Cited by 33 · see citing works
Couce, A., Alonso‐Rodríguez, N., Costas, C., Oliver, A., & Blázquez, J. (2016) · Clinical Microbiology and Infection · doi:10.1016/j.cmi.2016.03.008 · Cited by 26 · see citing works
Self-citationHobson, C. A., Bonacorsi, S., Hocquet, D., Baruchel, A., Fahd, M., Storme, T., Tang, R., Doit, C., Tenaillon, O., & Birgy, A. (2020) · Scientific Reports · doi:10.1038/s41598-020-57505-w · Cited by 26 · see citing works
Silver, L. L. (2017) · Topics in medicinal chemistry · doi:10.1007/7355_2017_24 · Cited by 15 · see citing works
Determinants of Genetic Diversity of Spontaneous Drug Resistance in Bacteria
Couce, A., Rodríguez-Rojas, A., & Blázquez, J. (2016) · Genetics · doi:10.1534/genetics.115.185355 · Cited by 12 · see citing works
Self-citationŁazowski, K. (2023) · Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis · doi:10.1016/j.mrfmmm.2023.111816 · Cited by 10 · see citing works
New approaches to mutation rate fold change in Luria–Delbrück fluctuation experiments
Zheng, Q. (2021) · Mathematical Biosciences · doi:10.1016/j.mbs.2021.108572 · Cited by 9 · see citing works
Majumdar, C., Nuñez, N. N., Raetz, A. G., Khuu, C., & David, S. S. (2018) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/bs.mie.2017.12.006 · Cited by 8 · see citing works
Antibacterial Discovery: Problems and Possibilities
Silver, L. L. (2013) · Antibiotics · doi:10.1002/9783527659685.ch2 · Cited by 3 · see citing works
Trends in the Use of Proper Methods for Estimating Mutation Rates in Fluctuation Experiments
Devin, G. A., & Couce, A. (2023) · Axioms · doi:10.3390/axioms12121100
Self-citation
- Authors
- Couce, A., & Blázquez, J.
- Affiliations
- Consejo Superior de Investigaciones Científicas (ES)
- Corresponding author
- Couce, Alejandro
- Venue
- Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
- Publisher
- Elsevier BV
- Published
- 2011-09
- Volume
- 714
- Issue
- 1-2
- Pages
- 26-32
- ISSN
- 0027-5107 (ISSN-L)
- 1386-1964
- OpenAlex
- W2056349084
- Cited by
- 13
- References
- 29
- Citations by year
- 2023: 2 · 2021: 1 · 2020: 1 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 2 · 2013: 2 · 2012: 1
- FWCI
- 0.60
- Type
- journal article
- Language
- en
- Open access
- green
- zenodo.org
- Licence
- Locations
- Mutation research. Fundamental and molecular mechanisms of mutagenesis (publishedVersion)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (acceptedVersion)
- Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, other-oa)
- Funders
- Seventh Framework Programme
- Instituto de Salud Carlos III
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Physical Sciences › Mathematics › Statistics and Probability › Probability and Statistical Research
- Keywords
- mutation rate estimation, mutant frequency, reproducibility, geometric mean, median, outlier removal, computer simulation
- MeSH terms
- Computer Simulation, Genetic Techniques, Mutation, Reproducibility of Results
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