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Most mutations are likely to be deleterious, and so the spontaneous mutation rate is generally held at a very low value. Nonetheless, evolutionary theory predicts that high mutation rates can evolve under certain circumstances. Empirical observations have previously been limited to short-term studies of the fates of mutator strains deliberately introduced into laboratory populations of Escherichia coli, and to the effects of intense selective events on mutator frequencies in E. coli. Here we report the rise of spontaneously originated mutators in populations of E. coli undergoing long-term adaptation to a new environment. Our results corroborate computer simulations of mutator evolution in adapting clonal populations, and may help to explain observations that associate high mutation rates with emerging pathogens and with certain cancers.

In sexual populations, beneficial mutations that occur in different lineages may be recombined into a single lineage. In asexual populations, however, clones that carry such alternative beneficial mutations compete with one another and, thereby, interfere with the expected progression of a given mutation to fixation. From theoretical exploration of such 'clonal interference', we have derived (1) a fixation probability for beneficial mutations, (2) an expected substitution rate, (3) an expected coefficient of selection for realized substitutions, (4) an expected rate of fitness increase, (5) the probability that a beneficial mutation transiently achieves polymorphic frequency (> or = 1%), and (6) the probability that a beneficial mutation transiently achieves majority status. Based on (2) and (3), we were able to estimate the beneficial mutation rate and the distribution of mutational effects from changes in mean fitness in an evolving E. coli population.

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We discuss the dynamics of adaptive evolution in asexual (clonal) populations. The classical 'periodic selection' model of clonal evolution assumed that beneficial mutations are very rare and therefore substitute unfettered into populations as occasional, isolated events. Newer models allow for the possibility that beneficial mutations are sufficiently common to coexist and compete for fixation within populations. Experimental evolution studies in microbes provide empirical support for stochastic models in which both selection and mutation are strong effects and clones compete for fixation; however, the relative importance of competition among clones bearing mutations of different selective effects versus competition among clones bearing multiple mutations remains unresolved. We provide some new theoretical results, moreover, suggesting that population dynamics consistent with the periodic selection model can arise even in a deterministic model that can accommodate a very high beneficial mutation rate.