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Pervasive genetic hitchhiking and clonal interference in forty evolving yeast populations


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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Figure 1: The fates of individual spontaneously arising mutations.
Figure 2: Statistical analysis across 40 replicate populations.
Figure 3: The dynamics of sequence evolution in BYB1-G07.
Figure 4: Genetic dissection of BYS1-A08.

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  1. 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)

    Article  ADS  CAS  Google Scholar 

  2. Strelkowa, N. & Lässig, M. Clonal interference in the evolution of influenza. Genetics 192, 671–682 (2012)

    Article  CAS  Google Scholar 

  3. Levin, B. R. & Bull, J. J. Short-sighted evolution and the virulence of pathogenic microorganisms. Trends Microbiol. 2, 76–81 (1994)

    Article  CAS  Google Scholar 

  4. Greaves, M. & Maley, C. C. Clonal evolution in cancer. Nature 481, 306–313 (2012)

    Article  ADS  CAS  Google Scholar 

  5. 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)

    Article  CAS  Google Scholar 

  6. Tenaillon, O. et al. The molecular diversity of adaptive convergence. Science 335, 457–461 (2012)

    Article  ADS  CAS  Google Scholar 

  7. 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)

    Article  ADS  CAS  Google Scholar 

  8. 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)

    Article  ADS  CAS  Google Scholar 

  9. Atwood, K. C., Schneider, L. K. & Ryan, F. J. Periodic selection in Escherichia coli. Proc. Natl Acad. Sci. USA 37, 146–155 (1951)

    Article  ADS  CAS  Google Scholar 

  10. Paquin, C. & Adams, J. Frequency of fixation of adaptive mutations is higher in evolving diploid than haploid yeast populations. Nature 302, 495–500 (1983)

    Article  ADS  CAS  Google Scholar 

  11. Joseph, S. B. & Hall, D. W. Spontaneous mutations in diploid Saccharomyces cerevisiae: more beneficial than expected. Genetics 168, 1817–1825 (2004)

    Article  Google Scholar 

  12. Perfeito, L., Fernandes, L., Mota, C. & Gordo, I. Adaptive mutations in bacteria: high rate and small effects. Science 317, 813–815 (2007)

    Article  ADS  CAS  Google Scholar 

  13. Gerrish, P. J. & Lenski, R. The fate of competing beneficial mutations in an asexual population. Genetica 102–103, 127–144 (1998)

    Article  Google Scholar 

  14. Desai, M. M. & Fisher, D. S. Beneficial mutation-selection balance and the effect of linkage on positive selection. Genetics 176, 1759–1798 (2007)

    Article  Google Scholar 

  15. Rouzine, I. M., Wakeley, J. & Coffin, J. The solitary wave of asexual evolution. Proc. Natl Acad. Sci. USA 100, 587–592 (2003)

    Article  ADS  CAS  Google Scholar 

  16. 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)

    Article  ADS  CAS  Google Scholar 

  17. Schiffels, S., Szöllősi, G. J., Mustonen, V. & Lässig, M. Emergent neutrality in adaptive asexual evolution. Genetics 189, 1361–1375 (2011)

    Article  Google Scholar 

  18. 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)

    Article  CAS  Google Scholar 

  19. 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)

    Article  ADS  CAS  Google Scholar 

  20. 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)

    Article  CAS  Google Scholar 

  21. Lang, G. I., Botstein, D. & Desai, M. M. Genetic variation and the fate of beneficial mutations in asexual populations. Genetics 188, 647–661 (2011)

    Article  Google Scholar 

  22. Barrick, J. E. et al. Genome evolution and adaptation in a long-term experiment with Escherichia coli. Nature 461, 1243–1247 (2009)

    Article  ADS  CAS  Google Scholar 

  23. 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)

    Article  CAS  Google Scholar 

  24. Dettman, J. R. et al. Evolutionary insight from whole-genome sequencing of experimentally evolved microbes. Mol. Ecol. 21, 2058–2077 (2012)

    Article  CAS  Google Scholar 

  25. Gresham, D. et al. The repertoire and dynamics of evolutionary adaptations to controlled nutrient-limited environments in yeast. PLoS Genet. 4, e1000303 (2008)

    Article  Google Scholar 

  26. Bollback, J. P. & Huelsenbeck, J. P. Clonal interference is alleviated by high mutation rates in large populations. Mol. Biol. Evol. 24, 1397–1406 (2007)

    Article  CAS  Google Scholar 

  27. Betancourt, A. J. Genomewide patterns of substitution in adaptively evolving populations of the RNA bacteriophage MS2. Genetics 181, 1535–1544 (2009)

    Article  CAS  Google Scholar 

  28. Miller, C. R., Joyce, P. & Wichman, H. A. Mutational effects and population dynamics during viral adaptation challenge current models. Genetics 187, 185–202 (2011)

    Article  Google Scholar 

  29. 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)

    Article  CAS  Google Scholar 

  30. Nik-Zainal, S. et al. The life history of 21 breast cancers. Cell 149, 994–1007 (2012)

    Article  CAS  Google Scholar 

  31. Li, H. et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics 25, 2078–2079 (2009)

    Article  Google Scholar 

  32. Li, H. & Durbin, R. Fast and accurate short read alignment with Burrows–Wheeler transform. Bioinformatics 25, 1754–1760 (2009)

    Article  CAS  Google Scholar 

  33. Robinson, J. T. et al. Integrative genomics viewer. Nature Biotechnol. 29, 24–26 (2011)

    Article  CAS  Google Scholar 

  34. 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)

    Article  Google Scholar 

  35. 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)

    Article  CAS  Google Scholar 

  36. Hartl, D. A Primer of Population Genetics. (Sinauer Associates, 2000)

    Google Scholar 

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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.

Author information

Authors and Affiliations



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.

Corresponding authors

Correspondence to Gregory I. Lang or Michael M. Desai.

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The authors declare no competing financial interests.

Additional information

Genome sequence data have been deposited to GenBank under the BioProject identifier PRJNA205542.

Supplementary information

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).

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