Multiple pathways of selected gene amplification during adaptive mutation

Elisabeth Kugelberg, Eric Kofoid, Andrew B. Reams, Dan I. Andersson, John R. Roth

Research output: Contribution to journalArticlepeer-review

76 Scopus citations


In a phenomenon referred to as "adaptive mutation," a population of bacterial cells with a mutation in the lac operon (lac-) accumulates Lac+ revenants during prolonged exposure to selective growth conditions (lactose). Evidence was provided that selective conditions do not increase the mutation rate but instead favor the growth of rare cells with a duplication of the leaky lac allele. A further increase in copy number (amplification) improves growth and increases the likelihood of a sequence change by adding more mutational targets to the clone (cells and lac copies per cell). These duplications and amplifications are described here. Before selection, cells with large (134-kb) lac duplications and long junction sequences (>1 kb) were common (0.2%). The same large repeats were found after selection in cells with a low-copy-number lac amplification. Surprisingly, smaller repeats (average, 34 kb) were found in high-copy-number amplifications. The small-repeat duplications form when deletions modify a preexisting large-repeat duplication. The shorter repeat size allowed higher lac amplification and better growth on lactose. Thus, selection favors a succession of gene-amplification types that make sequence changes more probable by adding targets. These findings are relevant to genetic adaptation in any biological systems in which fitness can be increased by adding gene copies (e.g., cancer and bacterial drug resistance).

Original languageEnglish (US)
Pages (from-to)17319-17324
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number46
StatePublished - Nov 14 2006


  • Gene duplication
  • Genetic adaptation
  • Genome instability
  • Mutation under selection
  • Natural selection

ASJC Scopus subject areas

  • Genetics
  • General


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