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Molecular characterization of clonal interference during adaptive evolution in asexual populations of Saccharomyces cerevisiae


The classical model of adaptive evolution in an asexual population postulates that each adaptive clone is derived from the one preceding it1. However, experimental evidence has suggested more complex dynamics2,3,4,5, with theory predicting the fixation probability of a beneficial mutation as dependent on the mutation rate, population size and the mutation's selection coefficient6. Clonal interference has been demonstrated in viruses7 and bacteria8 but not in a eukaryote, and a detailed molecular characterization is lacking. Here we use three different fluorescent markers to visualize the dynamics of asexually evolving yeast populations. For each adaptive clone within one of our evolving populations, we identified the underlying mutations, monitored their population frequencies and used microarrays to characterize changes in the transcriptome. These results represent the most detailed molecular characterization of experimental evolution to date and provide direct experimental evidence supporting both the clonal interference and the multiple mutation models.

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Figure 1: Population dynamics during evolution.
Figure 2: Relative fitness coefficients.
Figure 3: The frequencies of the observed alleles in the entire population and the frequencies of HXT amplifications within each of the subpopulations.

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This work was supported by US National Institutes of Health grants R01 HG003328 (G.S.) and F32 GM079113 (K.C.K.). We thank J. Ying for help with sample handling, E. Tanner for carrying out some of the gene expression microarray experiments, H. Tang for discussions on experimental design, J. Horecka for help with RT-PCR and F.Rosenzweig, B. Dunn and A. Sidow for comments on the manuscript.

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Authors and Affiliations



K.C.K. and G.S. conceived of and designed this study. K.C.K. performed all experiments and analyses. K.C.K. and G.S. wrote the manuscript.

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Correspondence to Gavin Sherlock.

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Supplementary Figures 1–4, Supplementary Tables 1–3 and Supplementary Methods (PDF 2042 kb)

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Kao, K., Sherlock, G. Molecular characterization of clonal interference during adaptive evolution in asexual populations of Saccharomyces cerevisiae. Nat Genet 40, 1499–1504 (2008).

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