Thus, in the case that the population structure can be described by the clonal replacement model, most mutations are lost and only one mutation can become established leading to one selective sweep at a time; therefore, the population is assumed to be homogeneous except

during the periods when the beneficial mutant is sweeping through the population. The second theory is called clonal interference (Fig. 1b) or sometimes called one-by-one clonal interference because http://www.selleckchem.com/products/bgj398-nvp-bgj398.html it is assumed that only one mutation can become fixed at a time. This occurs when mutations are established faster than the rate of fixations, multiple beneficial mutants can coexist and compete against each other until the one with the greatest fitness high throughput screening compounds advantage outcompetes all the other

genotypes and become the next founding genotype for subsequent evolution. The population is thus heterogeneous except immediately after the complete sweep by the fittest mutant. This theory focuses on the competition between mutations with different fitness effects (Gerrish & Lenski, 1998; Orr, 2000; Gerrish, 2001; Kim & Stephan, 2003; Campos & de Oliveira, 2004; Wilke, 2004) and assumes that mutations cannot be stacked in the same genetic background before the fixation of the most-fit mutation. However, the size of a typical laboratory microbial population is large enough to support multiple beneficial mutations occurring in same lineage before the first mutation in that lineage can fix (Desai & Fisher, 2007), which is the basis of the third theory: the ‘multiple-mutation’ model (Desai et al., 2007) (Fig. 1c). Multiple theoretical and experimental studies in other organisms have indirectly suggested the importance of this multiple-mutation effect (Yedid & Bell, 2001;

Shaver et al., 2002; Bachtrog & Gordo, 2004). A study using Saccharomyces cerevisiae evolving under carbon source limitation showed experimental support for this theory (Desai et al., 2007). Therefore, depending on the size of the population, the rate of mutation, time required for the establishment of a beneficial mutation, the fitness distribution of the mutations, and other important factors, evolution dynamics 6-phosphogluconolactonase in C. albicans during long-term exposure to antifungal agents may be described by one, or combinations, of the theories mentioned above. Because without exact genotype information, it is difficult to differentiate between the one-by-one clonal interference model and the multiple-mutation model, we will use the general term clonal interference to describe a heterogeneous evolving population structure. In the seminal paper on C. albicans adaptive evolution during antifungal drug exposure, Cowen et al. (2000) evolved 12 parallel populations, six in the absence and six in the presence of fluconazole for 330 generations, and isolated clones throughout the course of the evolution.