Mutators, population size, adaptive landscape and the adaptation of asexual populations of bacteria

Selection of mutator alleles, increasing the mutation rate up to 10,000-fol d, has been observed during in vitro experimental evolution. This spread is ascribed to the hitchhiking of mutator alleles with favorable mutations, a s demonstrated by a theoretical model using selective parameters correspond ing to such experiments. Observations of unexpectedly high frequencies of m utators in natural isolates suggest that the same phemonemon could occur in the wild. But it remains questionable whether realistic in natura paramete r values could also result in selection of mutators. In particular, the mai n parameters of adaptation, the size of the adapting population and the hei ght and steepness of the adaptive peak characterizing adaptation, are very variable in nature. By simulation approach, we studied the effect of these parameters on the selection of mutators in asexual populations, assuming ad ditive fitness. We show that the larger the population size, the more likel y the fixation of mutator alleles. At a large population size, at least fou r adaptive mutations are needed for mutator fixation; moreover, under stron ger selection stronger mutators are selected. We propose a model based on m ultiple mutations to illustrate how second-order selection can optimize pop ulation fitness when few favorable mutations are required for adaptation.