Article

The dynamics of molecular evolution over 60,000 generations

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Abstract

The outcomes of evolution are determined by a stochastic dynamical process that governs how mutations arise and spread through a population. However, it is difficult to observe these dynamics directly over long periods and across entire genomes. Here we analyse the dynamics of molecular evolution in twelve experimental populations of Escherichia coli, using whole-genome metagenomic sequencing at five hundred-generation intervals through sixty thousand generations. Although the rate of fitness gain declines over time, molecular evolution is characterized by signatures of rapid adaptation throughout the duration of the experiment, with multiple beneficial variants simultaneously competing for dominance in each population. Interactions between ecological and evolutionary processes play an important role, as long-term quasi-stable coexistence arises spontaneously in most populations, and evolution continues within each clade. We also present evidence that the targets of natural selection change over time, as epistasis and historical contingency alter the strength of selection on different genes. Together, these results show that long-term adaptation to a constant environment can be a more complex and dynamic process than is often assumed.

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Acknowledgements

We thank N. Hajela, A. N. Nguyen Ba, and E. Jerison for assistance. B.H.G. acknowledges support from the US National Science Foundation (DEB-1501580) and the Miller Institute for Basic Research in Science at the University of California Berkeley. R.E.L. acknowledges support from the US National Science Foundation (DEB-1451740) and BEACON Center for the Study of Evolution in Action (DBI-0939454). M.M.D. acknowledges support from the Simons Foundation (grant 376196), the US National Science Foundation (PHY-1313638), and the US National Institutes of Health (GM104239). Computational work was performed on the Odyssey cluster supported by the Research Computing Group at Harvard University.

Author information

Author notes

    • Benjamin H. Good
    •  & Michael J. McDonald

    These authors contributed equally to this work.

Affiliations

  1. Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, Massachusetts 02138, USA

    • Benjamin H. Good
    • , Michael J. McDonald
    •  & Michael M. Desai
  2. FAS Center for Systems Biology, Harvard University, Cambridge, Massachusetts 02138, USA

    • Benjamin H. Good
    • , Michael J. McDonald
    •  & Michael M. Desai
  3. Department of Physics, Harvard University, Cambridge, Massachusetts 02138, USA

    • Benjamin H. Good
    •  & Michael M. Desai
  4. Department of Physics, University of California Berkeley, Berkeley, California 94720, USA

    • Benjamin H. Good
  5. Department of Bioengineering, University of California Berkeley, Berkeley, California 94720, USA

    • Benjamin H. Good
  6. Centre for Geometric Biology, School of Biological Sciences, Monash University, Clayton, Victoria 3800, Australia

    • Michael J. McDonald
  7. Department of Molecular Biosciences, The University of Texas, Austin, Texas 78712, USA

    • Jeffrey E. Barrick
  8. BEACON Center for the Study of Evolution in Action, Michigan State University, East Lansing, Michigan 48824, USA

    • Jeffrey E. Barrick
    •  & Richard E. Lenski
  9. Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan 48824, USA

    • Richard E. Lenski

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Contributions

B.H.G., M.J.M., R.E.L. and M.M.D. designed the project; B.H.G. and M.J.M. conducted the experiments and generated the sequence data; B.H.G. and J.E.B. designed and conducted the bioinformatics analyses; B.H.G. developed theory and statistical methods; B.H.G., M.J.M., J.E.B., R.E.L. and M.M.D. analysed the data and wrote the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Michael M. Desai.

Reviewer Information Nature thanks R. Kishony, J. Plotkin, G. Sherlock and the other anonymous reviewer(s) for their contribution to the peer review of this work.

Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Extended data

Supplementary information

PDF files

  1. 1.

    Supplementary Information

    This file contains Supplementary Information sections 1-6, Supplementary Figures 1-19, full legends for Supplementary Tables 1-4 and a Data Availability Statement – see contents page for details.

  2. 2.

    Reporting Summary

CSV files

  1. 1.

    Supplementary Table 1

    This file contains a comma-separated list of metagenomic samples used in this study.

  2. 2.

    Supplementary Table 2

    This file contains a comma-separated list of clonal isolates used in this study.

  3. 3.

    Supplementary Table 3

    This file contains a comma-separated list of genes showing significant parallelism in the nonmutator populations.

  4. 4.

    Supplementary Table 4

    This file contains a comma-separated list of operons showing significant parallelism in the nonmutator populations.

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