Funding from the prestigious five-year Presidential Young Investigator award will be used to support research on the population biology of bacteria and their plasmids. Their large populations and short generations permit an experimental, not merely correlative, approach to the study of evolutionary processes. Research efforts will fall into four major areas: genetic basis of fitness in evolving populations of Escherichia coli, fitness consequences associated with alternative modes of regulation of tetracycline resistance genes in E. coli, evolution and genetics of an association between E. coli and plasmid pACYC184, and effects of recombinant functions (particularly chlorobenzoate degradation) on plasmid stability and host fitness in Pseudomonas species. Precise measurements of the effects of particular genetic variants, both chromosomal and extrachromosomal, on bacterial net growth, or relative fitness, are required for these projects.