Adaptive amplification: an inducible chromosomal instability mechanism

Cell. 2000 Nov 22;103(5):723-31. doi: 10.1016/s0092-8674(00)00176-8.


Adaptive mutation is an induced response to environmental stress in which mutation rates rise, producing permanent genetic changes that can adapt cells to stress. This contrasts with neo-Darwinian views of genetic change rates blind to environmental conditions. DNA amplification is a flexible, reversible genomic change that has long been postulated to be adaptive. We report the discovery of adaptive amplification at the lac operon in Escherichia coli. Additionally, we find that adaptive amplification is separate from, and does not lead to, adaptive point mutation. This contradicts a prevailing alternative hypothesis whereby adaptive mutation is normal mutability in amplified DNA. Instead, adaptive mutation and amplification are parallel routes of inducible genetic instability allowing rapid evolution under stress, and escape from growth inhibition.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Pair Mismatch
  • Blotting, Southern
  • Cell Division / genetics
  • Chromosomes*
  • DNA / biosynthesis*
  • DNA / metabolism
  • DNA Repair
  • Escherichia coli / genetics
  • Evolution, Molecular
  • Exodeoxyribonuclease V
  • Exodeoxyribonucleases / genetics
  • Lac Operon
  • Lactose / metabolism
  • Models, Genetic
  • Mutation*
  • Point Mutation
  • Salmonella / genetics
  • Time Factors


  • DNA
  • Exodeoxyribonucleases
  • Exodeoxyribonuclease V
  • Lactose