Mutation, Selection and Genetic Interactions in Bacteria Isabel Gordo, Instituto Gulbenkian deCieˆncia,Oeiras, Portugal Ana Sousa, Instituto Gulbenkian deCieˆncia,Oeiras, Portugal Mutation is the ultimate source of genetic variation. The rate at which new mutations typically occur, their effects on fitness and the strength and type of genetic inter- actions between different mutations are key for under- standing the evolution of any population. Estimates of these parameters in organisms such as bacteria will have a profound impact on our understanding of their biology, diversity, rate of speciation and in our health. Experi- mental evolution with bacteria presents us with the opportunity to directly measure these parameters and to test theoretical predictions about the genetic basis of adaptive evolution. Evidence has been increasing to sup- port the view that bacterial adaptation can be extra- ordinary fast, that competition between different adaptive mutations may be pervasive in bacterial popu- lations and that epistasis is very common and possibly biased towards antagonism in bacteria. Introduction For many bacterial species that reproduce mainly clonally, mutation is the primary source of variation on which nat- ural selection can act. But mutation is a two-edged sword: without it organisms cannot adapt, with it decreases in fitness are bound to occur. The genomic deleterious mutation rate (U d ) determines the mutational load of a population and therefore its ability to survive over many generations. The genomic beneficial mutation rate (U a ) is determinant on the speed at which populations adapt and colonise new environments. The fitness effect of a muta- tion, or its selection coefficient (s), is key in determining its fate. Very slightly deleterious mutations can fix, whereas mutations with strong detrimental effects are quickly eliminated. Very slightly beneficial mutations can easily be lost, whereas beneficial mutations with large effects have a high chance of fixing. Mutations with minute or no fitness effects accumulate at the rate at which they appear (U 0 ). Experimental estimates of a mutational effect require an empirical way to assay bacterial fitness. Typically that is accomplished by performing an experiment, where wild- type and mutant bacteria compete with one another in a given environment. From comparison of the numbers of each type before and after competition, a measure of the intrinsic growth rates per generation can be obtained and the effect of the mutation estimated from the differences in growth rates. Another common protocol is to compare the growth curves of the bacteria with different genotypes. Knowledge about rates, effects and genetic interactions of mutations is key to understand major features in evo- lution such as the evolution of sex, of diploidy, the main- tenance of genetic variation at the molecular level and the evolutionary fate of small populations among others. Bacterial Genomic Mutation Rate In 1930, RA Fisher asked a simple question: is there an optimal value for the mutation rate (U)? He argued for the existence of an optimum degree of mutability in asexual populations on the following grounds. If U is too low, then too few beneficial mutations occur and the species adap- tation is minute. If U is too high, many individuals carry deleterious mutations so that the beneficial mutations that occur will behave like a ruby in the rubbish: they will most likely fall on genetic backgrounds that already carry dele- terious alleles and will not be able to escape that back- ground. In between selection against deleterious mutations and selection for adapting to new environments, there will be an optimum U. Sixty years after Fisher wrote his mas- terpiece, an outstanding observation was made by Drake: ‘a nearly invariant microbial mutation rate appears to have evolved’. Drake (1991) found that for several Advanced article Article Contents . Introduction . Bacterial Genomic Mutation Rate . Fitness Effects of Mutations . Distribution of Effects of Mutations that Contribute to Adaptation . Genetic Interactions and Compensatory Evolution Online posting date: 19 th May 2010 ELS subject area: Evolution and Diversity of Life How to cite: Gordo, Isabel; and Sousa, Ana (May 2010) Mutation, Selection and Genetic Interactions in Bacteria. In: Encyclopedia of Life Sciences (ELS). John Wiley & Sons, Ltd: Chichester. DOI: 10.1002/9780470015902.a0022175 ENCYCLOPEDIA OF LIFE SCIENCES & 2010, John Wiley & Sons, Ltd. www.els.net 1