Nature 461, 1243-1247 (29 October 2009) | doi:10.1038/nature08480; Received 9 July 2009; Accepted 28 August 2009; Published online 18 October 2009; Corrected 29 October 2009

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

Jeffrey E. Barrick1,7, Dong Su Yu2,3,7, Sung Ho Yoon2, Haeyoung Jeong2, Tae Kwang Oh2,4, Dominique Schneider5, Richard E. Lenski1 & Jihyun F. Kim2,6

  1. Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan 48824, USA
  2. Industrial Biotechnology and Bioenergy Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong, Daejeon 305-806, Korea
  3. Department of Computer Science and Engineering, Chungnam National University, Yuseong, Daejeon 305-764, Korea
  4. 21C Frontier Microbial Genomics and Applications Center, Yuseong, Daejeon 305-806, Korea
  5. Institut Jean Roget, Laboratoire Adaptation et Pathogénie des Microorganismes, CNRS UMR 5163, Université Joseph Fourier, Grenoble 1, BP 170, F-38042 Grenoble cedex 9, France
  6. Functional Genomics Program, School of Science, University of Science and Technology, Yuseong, Daejeon 305-333, Korea
  7. These authors contributed equally to this work.

Correspondence to: Richard E. Lenski1Jihyun F. Kim2,6 Correspondence and requests for materials should be addressed to R.E.L. (Email: or J.F.K. (Email:


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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