Translation and Transcription Errors on Mutation Rates

A population of bacteria growing in a nonlimiting medium includes mutator bacteria and transient mututors defined as wild-type bacteria which, due to occasional transcription or translation errors, display a mutator phenotype. A semiquantitative theoretical analysis of the steady-state composition of an Escherichia coli population suggests that rue strong genotypic mutators produce about 3 X lo-’ of the single mutations arising in the population, while transient mutators produce at least 10% of the single mutations and more than 95% of the simultaneous double mutations. Numbers of mismatch repair proteins inherited by the offspring, proportions of lethal mutations and mortality rates are among the main parameters that influence the steady-state composition of the population. These results have implications for the experimental manipulation of mutation rates and the evolutionary fixation of frequent but nearly neutral mutations (e.g., synonymous codon substitutions). W HEN a bacterial mutant arises and is selected, did it originate from a standard wild-type bacterium or did it arise in a subpopulation with special properties? This question has been brought to the forefront of evolutionary thinking by the spectacular results of CAIRNS, OVERBAUGH and MILLER (1988) and HALL (1 990) demonstrating that some mutations are “more frequent when advantageous than when neutral” (HALL 1990). My purpose here is not to present alternatives to published models (e.g. , STAHL 1988) but to clarify some quantitative aspects of mutagenesis, and in particular to examine whether point mutations are usually contributed by standard bacteria or by a special class of error-prone bacteria. The bacterial types considered here are wild-type and genetically mutator bacteria as well as transient (or phenotypic) mutators: bacteria that are genetically wild type but, due to transcriptional or translational errors, have a reduced accuracy of replication or repair for one or two generations. STEADY STATE BETWEEN WILD-TYPE AND MUTATOR BACTERIA Let us consider a large population containing wildtype bacteria that produce mutations at a standard frequency f. The average number of mutations per replication of the entire genome is constant for a wide range of microorganisms, the best estimate beingf= 3 X 1 0-’ (DRAKE 1991). Estimates of this and other parameters used in this study are shown in Table 1. The population may also contain antimutator bacteria (which we neglect), transient mutators (not considered until the next section) and true mutators, producing Genetics 1 2 9 957-962 (November, 1991) mutations at a frequency kf. Let y and (1 y) represent the fractions of mutator and wild-type bacteria in the