| The dynamics of asexual populations are characterized by strong associations between alleles at different loci due to complete linkage. One consequence of complete linkage is the phenomenon known as hitchhiking, whereby a specified mutant allele is driven to high frequency or even fixation by a beneficial mutation to which it is linked. If the specified mutant allele confers a change in the mutation rate of the organism, then the fixation of that allele affects the mean mutation rate of the population. Observations of high mutation rates in evolving E. coli populations are consistent with the hypothesis that mutator alleles were fixed in these populations by hitchhiking. Theoretical exploration of the hitchhiking mechanism reveals its general significance for asexual evolution. I conclude that (i) mutation rates found in asexual populations are more likely to be determined by sporadic hitchhiking than by evolutionary "fine-tuning" as previous theoretical models would suggest, and (ii) there exists a most probable increase in mutation rate due to hitchhiking that is both positive and finite and its value is typically significant.;Another consequence of complete linkage is the phenomenon called "clonal interference", whereby the progression of one beneficial mutation to fixation is hindered or even prevented by competition with alternative beneficial mutations. From theoretical exploration of clonal interference, I derive several fundamental population-genetic parameters, as well as the probability that a beneficial mutation will transiently achieve polymorphic frequency. After treating the case in which an unlimited number of beneficial mutations are available, I treat the case in which that number is limited. From these developments, I solve the inverse problem of estimating the following parameters from fitness data of evolving E. coli populations: (i) beneficial mutation rate, (ii) the distribution of mutational effects, and (iii) the number of available beneficial mutations for the case in which this number is limited. Salient conclusions from both theoretical treatments are (i) adaptive evolution of asexual populations is characteristically punctuated with short bursts of rapid change followed by long periods of stasis regardless of population size or mutation rate, (ii) in identical environments, the trajectory of adaptive evolution of large, parallel populations is highly repeatable due to clonal interference, (iii) the rate of fitness improvement is an increasing function of both mutation rate and population size, but the function is decelerating so that the rate of adaptive evolution is constrained by a "speed limit", and (iv) with significant probability, clonal interference may transiently maintain fitness variants at polymorphic frequencies. |
