Summary: “Evolution of mutation rates in bacteria” (Denamur and Matic 2006)
This is an “executive summary” of Denamur and Matic (2006), which is a review of the literature on the evolution of the mutation rate in bactera.
- Deleterious mutations are 100,000-fold more frequent than beneficial mutations in E. coli.
- Mutators have been found in various species of bacteria in frequencies of 0.1-60%: 1% strong mutators, 10-30% weak mutators (Matic et al. 1997; Baquero et al. 2004).
- These frequencies are higher than expected under a mutation-selection balance (MSB) - Boe et al. (2000) estimated the mutator fraction at 0.00003.
- Mutator alleles are mainly mutants in the mismatch repair (MMR) system (mutS, mutL) - see the article for more information on the operation of these genes and the MMR system).
- Rate increases by these MMR mutants: 100-fold increase in transitions, 1,000-fold increase in frameshifts and 10-1,000-fold increase in chromosomal rearrangements.
- MMR mutatns arise by different mutation types. The rate of non-mutator to mutator was estimated by Boe et al. (2000) to be 0.000005 per generation.
- What can cause the frequency of MMR mutants to be higher than that expected under a MSB?
- The first explanation was rejected: Several studies found that mutators are advanageous only when the ratio of mutator to non-mutator is such that beneficial mutations are more likely to be generated by mutators than by non-mutators3.
- The second explanation is stonger in bacteria than in other species because recombination rates are low and therefore mutators are not separated from the beneficial mutations they generate.
- Although mutators can reach high frequencies in adaptive evolution, they accumulate deleterious mutations and decline in frequency in a constant environment.
- Migration to new environments can change a beneficial mutation to neutral or deleterious.
- Mutators are more vulnerable to Muller’s ratchet due to faster accumulation of deleterious mutations (Funchain et al. 2000).
- Beneficial mutations can move to non-mutator background by horizontal gene transfer or back/compensatory mutation at the mutator locus.
- Local mutators - DNA sequences that induce high mutation rates in their neighborhoods - were found in virulent loci.
- There are over 20 loci associated with mutator phenotypes, probably with different direct effects on mutation rate and fitness and with different pleiotropic effects - for example, mutT increases the mutation and adaptation rate but also increases transcriptional error rate (Taddei, Hayakawa, et al. 1997).
- MMR mutants are special because they also increase recombination rates which can help in adaptation (Funchain et al. 2001). High recombination rates can also help to restore non-mutator alleles after adaptation is complete4.
- Most mutators were found in pathogenic bacteria.
- Some mutators were correlated in natural populations with antibiotic resistance, however not strong mutators: the latter are probably counter-selected after adaptation and are therefore not found in natural population (Taddei, Radman, et al. 1997).
Baquero, María-Rosario, Annika I Nilsson, María del Carmen Turrientes, Dorthe Sandvang, Juan-Carlos Galán, Jose Luís Martínez, Niels Frimodt-Møller, Fernando Baquero, and Dan I. Andersson. 2004. “Polymorphic mutation frequencies in <i>Escherichia coli</i>: emergence of weak mutators in clinical isolates.” Journal of Bacteriology 186 (16): 5538–42. doi:10.1128/JB.186.16.5538-5542.2004.
Boe, L, M Danielsen, S Knudsen, J B Petersen, J Maymann, and P R Jensen. 2000. “The frequency of mutators in populations of Escherichia coli.” Mutation Research 448 (1). Elsevier: 47–55. doi:10.1016/S0027-5107(99)00239-0.
Dawson, Kevin J. 1998. “Evolutionarily stable mutation rates.” Journal of Theoretical Biology 194 (1): 143–57. doi:10.1006/jtbi.1998.0752.
Denamur, Erick, and Ivan Matic. 2006. “Evolution of mutation rates in bacteria.” Molecular Microbiology 60 (4): 820–7. doi:10.1111/j.1365-2958.2006.05150.x.
Funchain, Pauline, A Yeung, J Stewart, W M Clendenin, and J H Miller. 2001. “Amplification of mutator cells in a population as a result of horizontal transfer.” Journal of Bacteriology 183 (12): 3737–41. doi:10.1128/JB.183.12.3737-3741.2001.
Funchain, Pauline, Annie Yeung, Jean Lee Stewart, Rose Lin, Malgorzata M. Slupska, and Jeffrey H. Miller. 2000. “The consequences of growth of a mutator strain of <i>Escherichia coli</i> as measured by loss of function among multiple gene targets and loss of fitness.” Genetics 154 (3): 959–70. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1461004.
Leigh, Egbert Giles Jr. 1973. “The evolution of mutation rates.” Genetics 73 (April): Suppl 73:1–18. http://www.ncbi.nlm.nih.gov/pubmed/4711556.
Matic, Ivan, François Taddei, Bertrand Picard, Catherine Doit, Edouard Bingen, Erick Denamur, and Jacques Elion. 1997. “Highly Variable Mutation Rates in Commensal and Pathogenic Escherichia coli.” Science 277 (5333): 1833–34. doi:10.1126/science.277.5333.1833.
Taddei, François, H Hayakawa, M Bouton, A Cirinesi, Ivan Matic, M Sekiguchi, and M Radman. 1997. “Counteraction by MutT protein of transcriptional errors caused by oxidative damage.” Science 278 (5335): 128–30. doi:10.1126/science.278.5335.128.
Taddei, François, Miroslav Radman, John Maynard Smith, Bruno Toupance, Pierre-Henri Gouyon, and Bernard Godelle. 1997. “Role of mutator alleles in adaptive evolution.” Nature 387 (6634): 700–702. doi:10.1038/42696.
Torres-Barceló, Clara, Gabriel Cabot, Antonio Oliver, Angus Buckling, and R. Craig MacLean. 2013. “A trade-off between oxidative stress resistance and DNA repair plays a role in the evolution of elevated mutation rates in bacteria.” Proceedings of the Royal Society B: Biological Sciences 280 (1757): 20130007. doi:10.1098/rspb.2013.0007.
Cost of DNA replication fidelity (Dawson 1998)↩
Second-order selection (for example, (Leigh 1973))↩
But see (Torres-Barceló et al. 2013) which showed that P. aeruginosa mutators are oxidative-stress resistant↩
Rise and fall of the mutator allele (Taddei, Radman, et al. 1997)↩