Abstract
The dynamics of adaptation determine which mutations fix in a population, and hence how reproducible evolution will be. This is central to understanding the spectra of mutations recovered in the evolution of antibiotic resistance1, the response of pathogens to immune selection2,3, and the dynamics of cancer progression4,5. In laboratory evolution experiments, demonstrably beneficial mutations are found repeatedly6,7,8, but are often accompanied by other mutations with no obvious benefit. Here we use whole-genome whole-population sequencing to examine the dynamics of genome sequence evolution at high temporal resolution in 40 replicate Saccharomyces cerevisiae populations growing in rich medium for 1,000 generations. We find pervasive genetic hitchhiking: multiple mutations arise and move synchronously through the population as mutational ‘cohorts’. Multiple clonal cohorts are often present simultaneously, competing with each other in the same population. Our results show that patterns of sequence evolution are driven by a balance between these chance effects of hitchhiking and interference, which increase stochastic variation in evolutionary outcomes, and the deterministic action of selection on individual mutations, which favours parallel evolutionary solutions in replicate populations.
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References
Weinreich, D. M., Delaney, N. F., DePristo, M. A. & Hartl, D. L. Darwinian evolution can follow only very few mutational paths to fitter proteins. Science 312, 111–114 (2006)
Strelkowa, N. & Lässig, M. Clonal interference in the evolution of influenza. Genetics 192, 671–682 (2012)
Levin, B. R. & Bull, J. J. Short-sighted evolution and the virulence of pathogenic microorganisms. Trends Microbiol. 2, 76–81 (1994)
Greaves, M. & Maley, C. C. Clonal evolution in cancer. Nature 481, 306–313 (2012)
Sprouffske, K., Merlo, L. M. F., Gerrish, P. J., Maley, C. C. & Sniegowski, P. D. Cancer in light of experimental evolution. Curr. Biol. 22, R762–R771 (2012)
Tenaillon, O. et al. The molecular diversity of adaptive convergence. Science 335, 457–461 (2012)
Woods, R., Schneider, D., Winkworth, C. L., Riley, M. A. & Lenski, R. E. Tests of parallel molecular evolution in a long-term experiment with Escherichia coli. Proc. Natl Acad. Sci. USA 103, 9107–9112 (2006)
Saxer, G., Doebeli, M. & Travisano, M. The repeatability of adaptive radiation during long-term experimental evolution of Escherichia coli in a multiple nutrient environment. PLoS ONE 5, e14184 (2010)
Atwood, K. C., Schneider, L. K. & Ryan, F. J. Periodic selection in Escherichia coli. Proc. Natl Acad. Sci. USA 37, 146–155 (1951)
Paquin, C. & Adams, J. Frequency of fixation of adaptive mutations is higher in evolving diploid than haploid yeast populations. Nature 302, 495–500 (1983)
Joseph, S. B. & Hall, D. W. Spontaneous mutations in diploid Saccharomyces cerevisiae: more beneficial than expected. Genetics 168, 1817–1825 (2004)
Perfeito, L., Fernandes, L., Mota, C. & Gordo, I. Adaptive mutations in bacteria: high rate and small effects. Science 317, 813–815 (2007)
Gerrish, P. J. & Lenski, R. The fate of competing beneficial mutations in an asexual population. Genetica 102–103, 127–144 (1998)
Desai, M. M. & Fisher, D. S. Beneficial mutation-selection balance and the effect of linkage on positive selection. Genetics 176, 1759–1798 (2007)
Rouzine, I. M., Wakeley, J. & Coffin, J. The solitary wave of asexual evolution. Proc. Natl Acad. Sci. USA 100, 587–592 (2003)
Good, B. H., Rouzine, I. M., Balick, D. J., Hallatschek, O. & Desai, M. M. The rate of adaptation and the distribution of fixed beneficial mutations in asexual populations. Proc. Natl Acad. Sci. USA 109, 4950–4955 (2012)
Schiffels, S., Szöllősi, G. J., Mustonen, V. & Lässig, M. Emergent neutrality in adaptive asexual evolution. Genetics 189, 1361–1375 (2011)
Desai, M. M., Fisher, D. S. & Murray, A. W. The speed of evolution and maintenance of variation in asexual populations. Curr. Biol. 17, 385–394 (2007)
de Visser, J. A. G. M., Zeyl, C. W., Gerrish, P. J., Blanchard, J. L. & Lenski, R. E. Diminishing returns from mutation supply rate in asexual populations. Science 283, 404–406 (1999)
Kao, K. C. & Sherlock, G. Molecular Characterization of clonal interference during adaptive evolution in asexual populations of Saccharomyces cerevisiae. Nature Genet. 40, 1499–1504 (2008)
Lang, G. I., Botstein, D. & Desai, M. M. Genetic variation and the fate of beneficial mutations in asexual populations. Genetics 188, 647–661 (2011)
Barrick, J. E. et al. Genome evolution and adaptation in a long-term experiment with Escherichia coli. Nature 461, 1243–1247 (2009)
Barrick, J. E. & Lenski, R. E. Genome-wide mutational diversity in an evolving population of Escherichia coli. Cold Spring Harb. Symp. Quant. Biol. 74, 119–129 (2009)
Dettman, J. R. et al. Evolutionary insight from whole-genome sequencing of experimentally evolved microbes. Mol. Ecol. 21, 2058–2077 (2012)
Gresham, D. et al. The repertoire and dynamics of evolutionary adaptations to controlled nutrient-limited environments in yeast. PLoS Genet. 4, e1000303 (2008)
Bollback, J. P. & Huelsenbeck, J. P. Clonal interference is alleviated by high mutation rates in large populations. Mol. Biol. Evol. 24, 1397–1406 (2007)
Betancourt, A. J. Genomewide patterns of substitution in adaptively evolving populations of the RNA bacteriophage MS2. Genetics 181, 1535–1544 (2009)
Miller, C. R., Joyce, P. & Wichman, H. A. Mutational effects and population dynamics during viral adaptation challenge current models. Genetics 187, 185–202 (2011)
Wichman, H. A., Badgett, M. R., Scott, L. A., Boulianne, C. M. & Bull, J. J. Different trajectories of parallel evolution during viral adaptation. Science 285, 422–424 (1999)
Nik-Zainal, S. et al. The life history of 21 breast cancers. Cell 149, 994–1007 (2012)
Li, H. et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics 25, 2078–2079 (2009)
Li, H. & Durbin, R. Fast and accurate short read alignment with Burrows–Wheeler transform. Bioinformatics 25, 1754–1760 (2009)
Robinson, J. T. et al. Integrative genomics viewer. Nature Biotechnol. 29, 24–26 (2011)
Thorvaldsdóttir, H., Robinson, J. T. & Mesirov, J. P. Integrative Genomics Viewer (IGV): high-performance genomics data visualization and exploration. Brief. Bioinform. 14, 178–192 (2013)
Altschul, S. F., Gish, W., Miller, W., Myers, E. W. & Lipman, D. J. Basic local alignment search tool. J. Mol. Biol. 215, 403–410 (1990)
Hartl, D. A Primer of Population Genetics. (Sinauer Associates, 2000)
Acknowledgements
We thank the production team led by L. Fulton and R. Fulton at the Genome Institute at Washington University for sample management and data production, and E. Lobos for coordinating the project. We thank L. Parsons and J. Wiggins for assistance with data management, P. Gibney for assistance with sample preparation, and T. DeCoste for assistance with flow cytometry. We thank K. Kosheleva for discussions, and A. Murray, C. Marx, M. McDonald, G. Sherlock and D. Kvitek for comments on the manuscript. D.P.R. acknowledges support from an NSF Graduate Research Fellowship. D.B. acknowledges support from NIGMS Centers of Excellence grant GM071508 and NIH grant GM046406. M.M.D. acknowledges support from the James S. McDonnell Foundation, the Alfred P. Sloan Foundation, and the Harvard Milton Fund.
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G.I.L., D.B. and M.M.D. designed the project; E.S. and G.M.W. generated the sequencing data; G.I.L., D.P.R., M.J.H. and M.M.D. analysed the sequencing data; G.I.L. performed the experiments; G.I.L., D.P.R., D.B. and M.M.D. wrote the paper. Co-senior authors, D.B. and M.M.D.
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Additional information
Genome sequence data have been deposited to GenBank under the BioProject identifier PRJNA205542.
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Supplementary Information
This file contains Supplementary Tables 2-3 (see separate file for Supplementary Table 1) and Supplementary Figures 1-3. (PDF 6136 kb)
Supplementary Table 1
This file contains details of the 1,020 mutations identified in the 40 sequenced populations. It also contains complete descriptions of all mutations we observed in all 40 populations, and their frequency trajectories over the 1,000 generations of the experiment, as estimated by both independent pipelines (Methods). (XLSX 412 kb)
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Lang, G., Rice, D., Hickman, M. et al. Pervasive genetic hitchhiking and clonal interference in forty evolving yeast populations. Nature 500, 571–574 (2013). https://doi.org/10.1038/nature12344
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DOI: https://doi.org/10.1038/nature12344
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