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      Molecular Characterization of Clonal Interference during Adaptive Evolution in Asexual Populations of Saccharomyces cerevisiae

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      1 , 2
      Nature genetics

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          Abstract

          The classical model of adaptive evolution in an asexual population postulates that each adaptive clone is derived from the one preceding it 1. However, experimental evidence suggests more complex dynamics 2- 5 with theory predicting the fixation probability of a beneficial mutation as dependent on the mutation rate, population size, and the mutation's selection coefficient 6. Clonal interference has been demonstrated in viruses 7 and bacteria 8, but has not been demonstrated in a eukaryote and a detailed molecular characterization is lacking. Here we use different fluorescent markers to visualize the dynamics of asexually evolving yeast populations. For each adaptive clone within one of our evolving populations, we have identified the underlying mutations, monitored their population frequencies and used microarrays to characterize changes in the transcriptome. These data provide the most detailed molecular characterization of an experimental evolution to date, and provide direct experimental evidence supporting both the clonal interference and the multiple mutation models.

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          Most cited references30

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          Some Genetic Aspects of Sex

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            Beneficial mutation selection balance and the effect of linkage on positive selection.

            When beneficial mutations are rare, they accumulate by a series of selective sweeps. But when they are common, many beneficial mutations will occur before any can fix, so there will be many different mutant lineages in the population concurrently. In an asexual population, these different mutant lineages interfere and not all can fix simultaneously. In addition, further beneficial mutations can accumulate in mutant lineages while these are still a minority of the population. In this article, we analyze the dynamics of such multiple mutations and the interplay between multiple mutations and interference between clones. These result in substantial variation in fitness accumulating within a single asexual population. The amount of variation is determined by a balance between selection, which destroys variation, and beneficial mutations, which create more. The behavior depends in a subtle way on the population parameters: the population size, the beneficial mutation rate, and the distribution of the fitness increments of the potential beneficial mutations. The mutation-selection balance leads to a continually evolving population with a steady-state fitness variation. This variation increases logarithmically with both population size and mutation rate and sets the rate at which the population accumulates beneficial mutations, which thus also grows only logarithmically with population size and mutation rate. These results imply that mutator phenotypes are less effective in larger asexual populations. They also have consequences for the advantages (or disadvantages) of sex via the Fisher-Muller effect; these are discussed briefly.
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              The fate of competing beneficial mutations in an asexual population.

              In sexual populations, beneficial mutations that occur in different lineages may be recombined into a single lineage. In asexual populations, however, clones that carry such alternative beneficial mutations compete with one another and, thereby, interfere with the expected progression of a given mutation to fixation. From theoretical exploration of such 'clonal interference', we have derived (1) a fixation probability for beneficial mutations, (2) an expected substitution rate, (3) an expected coefficient of selection for realized substitutions, (4) an expected rate of fitness increase, (5) the probability that a beneficial mutation transiently achieves polymorphic frequency (> or = 1%), and (6) the probability that a beneficial mutation transiently achieves majority status. Based on (2) and (3), we were able to estimate the beneficial mutation rate and the distribution of mutational effects from changes in mean fitness in an evolving E. coli population.
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                Author and article information

                Journal
                9216904
                2419
                Nat Genet
                Nature genetics
                1061-4036
                1546-1718
                24 October 2008
                December 2008
                1 June 2009
                : 40
                : 12
                : 1499-1504
                Affiliations
                [1 ]Department of Chemical Engineering, Texas A&M University, College Station, TX 77843, USA
                [2 ]Department of Genetics, Stanford University, Stanford, CA 94305-5120, USA
                Author notes
                Correspondence and requests for materials should be addressed to G.S. ( sherlock@ 123456genome.stanford.edu ) and K.K. ( katy@ 123456chemail.tamu.edu ).
                Article
                nihpa75653
                10.1038/ng.280
                2596280
                19029899
                d6d1ec1e-4b8c-4a84-a4ce-9d306ad98b60
                History
                Funding
                Funded by: National Human Genome Research Institute : NHGRI
                Funded by: National Institute of General Medical Sciences : NIGMS
                Award ID: R01 HG003328-01A1 ||HG
                Funded by: National Human Genome Research Institute : NHGRI
                Funded by: National Institute of General Medical Sciences : NIGMS
                Award ID: F32 GM079113-01A1 ||GM
                Categories
                Article

                Genetics
                Genetics

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