Date of Award


Degree Type


Degree Name

Doctor of Philosophy (PhD)

Graduate Group


First Advisor

Paul Sniegowski


Simulations of asexual populations undergoing continual adaptation present a definite prediction: mutator hitchhiking should drive the mutation rate upwards in an asexual population until it reaches an intolerable level, at which point the population will be driven extinct. Experimental studies have shown that a mutator allele can readily hitchhike to fixation with beneficial mutations in an asexual population having a low, wild-type mutation rate. Using Eshcerichia coli, I show that a genotype bearing two mutator alleles can supplant an asexual population already fixed for one mutator allele. My results provide experimental support for recent theory predicting that mutator alleles will tend to accumulate in asexual populations by hitchhiking with beneficial mutations, causing an ever-higher genomic mutation rate. Interestingly, results from recent simulations also suggest that the deleterious mutational load which accompanies an increased mutation rate is not immediately incurred. The delay in accruing a mutational load may potentially allow a succession of mutator hitch hiking events to occur before the cost of the initial hitchhiking event is incurred. Ultimately, mutation rates in asexual populations may evolve upwards to a rate that threatens extinction due to overwhelming mutational pressure. To test this prediction, I established independent populations of E. coli bearing either a single- or double-mutator genotype and propagated them for several thousand generations. At the conclusion of the experiment, the growth rate of the single-mutator populations had risen substantially, consistent with the substitution of beneficial mutations; in contrast, the growth rate of the double-mutator populations had fallen significantly, consistent with erosion of fitness by deleterious mutations. In addition, both sets of populations had maintained the mutation rate present at the outset of the experiment. Strikingly, the experiment seems to have provided evidence of mutation-driven fitness decline in the double-mutator populations despite the presence of beneficial mutations. I address the experimental results in the context of theoretical predication of fitness decline at a high mutation rates.