Genome evolution and adaptation in a long-term experiment with Escherichia coli

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The relationship between rates of genomic evolution and organismal adaptation remains uncertain, despite considerable interest. The feasibility of obtaining genome sequences from experimentally evolving populations offers the opportunity to investigate this relationship with new precision. Here we sequence genomes sampled through 40,000 generations from a laboratory population of Escherichia coli. Although adaptation decelerated sharply, genomic evolution was nearly constant for 20,000 generations. Such clock-like regularity is usually viewed as the signature of neutral evolution, but several lines of evidence indicate that almost all of these mutations were beneficial. This same population later evolved an elevated mutation rate and accumulated hundreds of additional mutations dominated by a neutral signature. Thus, the coupling between genomic and adaptive evolution is complex and can be counterintuitive even in a constant environment. In particular, beneficial substitutions were surprisingly uniform over time, whereas neutral substitutions were highly variable.

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Figure 1: Mutations found by sequencing genomes sampled between 2,000 and 20,000 generations from an evolution experiment with E. coli.
Figure 2: Rates of genomic evolution and fitness improvement.

Change history

  • 29 October 2009

    In the paragraph beginning, 'Several of the long-term populations...', '(599 of 597)' was replaced by '(553 of 599)' on 29 October 2009.


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We thank collaborators in the Lenski and Schneider laboratories for sharing unpublished data; N. Hajela and J. I. Lee for isolation of genomic DNA; C. T. Brown, C. Epstein, C. H. Lee and J. Plotkin for discussion; N. Hajela, L. Ekunwe and S. Simpson for years of technical assistance with the long-term lines; and W. J. Dittmar for assistance with fluctuation tests. We acknowledge support from the DARPA ‘Fun Bio’ Program (to R.E.L.); the US National Science Foundation (to J.E.B. and R.E.L.); the Agence Nationale de la Recherche Programme ‘Génomique Microbienne à Grande Echelle’, Centre National de la Recherche Scientifique, and Université Joseph Fourier (to D.S.); and the 21C Frontier Microbial Genomics and Applications Center Program, Ministry of Education, Science and Technology, Republic of Korea (to J.F.K.).

Author Contributions R.E.L., D.S. and J.F.K. conceived the project and its components. D.S.Y., J.E.B., S.H.Y., H.J., T.K.O. and J.F.K. performed the genome sequencing and confirmatory analyses. D.S. sequenced specific genes in other populations and performed additional molecular procedures. J.E.B. developed code for data analyses and statistical simulations. R.E.L. directs the long-term experiment while J.F.K. directed the genomics work. R.E.L., J.E.B. and J.F.K. analysed the data and wrote the paper. J.E.B., D.S.Y., S.H.Y., R.E.L., D.S. and J.F.K. prepared figures and tables.

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Correspondence to Richard E. Lenski or Jihyun F. Kim.

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

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