Role of mutator alleles in adaptive evolution

Abstract

Because most newly arising mutations are neutral or deleterious, it has been argued that the mutation rate has evolved to be as low as possible, limited only by the cost of error-avoidance and error-correction mechanisms. But up to one per cent of natural bacterial isolates are 'mutator' clones that have high mutation rates. We consider here whether high mutation rates might play an important role in adaptive evolution. Models of large, asexual, clonal populations adapting to a new environment show that strong mutator genes (such as those that increase mutation rates by 1,000-fold) can accelerate adaptation, even if the mutator gene remains at a very low frequency (for example, 10[-5]). Less potent mutators (10 to 100-fold increase) can become fixed in a fraction of finite populations. The parameters of the model have been set to values typical for Escherichia coli cultures, which behave in a manner similar to the model in long-term adaptation experiments.

DNA polymerases in adaptive immunity

“…By so doing, mutagenesis is favoured over cell death, and it has been widely discussed that mutator phenotypes have an adaptive value in prokaryotes 118,119 . The paradigm of the XPV syndrome, in which a TLS polymerase deficiency results in sunlight sensitivity and an increased risk of skin cancers, suggests an alternative scenario in higher organisms.…”

Fixation probability of rare nonmutator and evolution of mutation rates

“…As the mutators produce not only deleterious but also beneficial mutations at a higher rate than the nonmutators, the mutator allele can hitchhike to fixation with favorable mutations (Smith and Haigh 1974; Taddei et al. 1997). However, once the population has reached a high fitness level, high mutation rates are detrimental because most mutations will now be deleterious, and in such a situation, the mutation rate is expected to decrease (Liberman and Feldman 1986).…”

“…An important difference between the previous works on mutator hitchhiking (Taddei et al. 1997; Andre and Godelle 2006; Wylie et al. 2009; Desai and Fisher 2011) and our study is that here the mutator population is assumed to be at mutation‐selection equilibrium and is therefore not under positive selection.…”

“…Our study thus identifies the conditions under which the spread of nonmutators is suppressed in the absence of positive selection, and complements earlier works in which a mutator hitchhikes with beneficial mutations to fixation (Taddei et al. 1997; Andre and Godelle 2006; Wylie et al. 2009; Desai and Fisher 2011).…”

Adaptive dynamics of unstable cancer populations: The canonical equation

“…On the one hand, this means that we are able to obtain analytical expressions for the exponential evolution and saturation of the mutation probability, which could eventually be used when studying in vitro long‐term evolutionary experiments with cancer populations, using serial transfer methods similar to those performed on viruses (see e.g., Drake, 1993; Sanjuán et al., 2010; Solé et al., 1999) or bacterial populations (see e.g., Moxon et al., 1994; Sniegowski, Gerrish, & Lenski, 1997; Barrick et al., 2009 for experiments and Taddei et al., 1997 for an early model for mutator alleles). Given the remarkable similarities found between microbial communities found both in the ecological and evolutionary time scales (Lambert et al., 2011), it would be worth exploring the evolution of instability of cancer cell cultures over many transfer generations (Langdon, 2004).…”