Yoav Ram's blog

Posted Sun 14 July 2013

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.

  1. Deleterious mutations are 100,000-fold more frequent than beneficial mutations in E. coli.
  2. 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).
  3. These frequencies are higher than expected under a mutation-selection balance (MSB) - Boe et al. (2000) estimated the mutator fraction at 0.00003.
  4. 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).
  5. 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.
  6. 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.
  7. What can cause the frequency of MMR mutants to be higher than that expected under a MSB?
    • Higher replication rates due to the absence of the metabolic load imposed by DNA repair enzymes1
    • Higher adaptation rate due to the faster generation of beneficial mutations2
  8. 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.
  9. 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.
  10. Although mutators can reach high frequencies in adaptive evolution, they accumulate deleterious mutations and decline in frequency in a constant environment.
  11. Migration to new environments can change a beneficial mutation to neutral or deleterious.
  12. Mutators are more vulnerable to Muller’s ratchet due to faster accumulation of deleterious mutations (Funchain et al. 2000).
  13. Beneficial mutations can move to non-mutator background by horizontal gene transfer or back/compensatory mutation at the mutator locus.
  14. Local mutators - DNA sequences that induce high mutation rates in their neighborhoods - were found in virulent loci.
  15. 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).
  16. 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.
  17. Most mutators were found in pathogenic bacteria.
  18. 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.

  1. Cost of DNA replication fidelity (Dawson 1998)

  2. Second-order selection (for example, (Leigh 1973))

  3. But see (Torres-Barceló et al. 2013) which showed that P. aeruginosa mutators are oxidative-stress resistant

  4. Rise and fall of the mutator allele (Taddei, Radman, et al. 1997)

Category: evolution