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, 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?
- Higher replication rates due to the absence of the metabolic load imposed by DNA repair enzymes
- Higher adaptation rate due to the faster generation of beneficial mutations
- 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-mutators.
- 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 et al., Science, 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 complete.
- 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 et al., Nature, 1997).