AID mutates E. coli suggesting a DNA deamination mechanism for antibody diversification

Nature. 2002 Jul 4;418(6893):99-103. doi: 10.1038/nature00862.


After gene rearrangement, immunoglobulin variable genes are diversified by somatic hypermutation or gene conversion, whereas the constant region is altered by class-switch recombination. All three processes depend on activation-induced cytidine deaminase (AID), a B-cell-specific protein that has been proposed (because of sequence homology) to function by RNA editing. But indications that the three gene diversification processes might be initiated by a common type of DNA lesion, together with the proposal that there is a first phase of hypermutation that targets dC/dG, suggested to us that AID may function directly at dC/dG pairs. Here we show that expression of AID in Escherichia coli gives a mutator phenotype that yields nucleotide transitions at dC/dG in a context-dependent manner. Mutation triggered by AID is enhanced by a deficiency of uracil-DNA glycosylase, which indicates that AID functions by deaminating dC residues in DNA. We propose that diversification of functional immunoglobulin genes is triggered by AID-mediated deamination of dC residues in the immunoglobulin locus with the outcome--that is, hypermutation phases 1 and 2, gene conversion or switch recombination--dependent on the way in which the initiating dU/dG lesion is resolved.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amination
  • Amino Acid Sequence
  • Base Sequence
  • Cytidine Deaminase / genetics
  • Cytidine Deaminase / metabolism*
  • DNA / chemistry
  • DNA / genetics*
  • DNA / metabolism*
  • DNA Glycosylases*
  • DNA, Bacterial / chemistry
  • DNA, Bacterial / genetics
  • DNA, Bacterial / metabolism
  • DNA-Directed RNA Polymerases / genetics
  • Escherichia coli / enzymology
  • Escherichia coli / genetics*
  • Gene Conversion / genetics
  • Gene Frequency
  • Genes, Bacterial / genetics
  • Genes, Immunoglobulin / genetics
  • Humans
  • Immunoglobulin Switch Region / genetics
  • Models, Genetic*
  • Molecular Sequence Data
  • Mutagenesis / genetics*
  • N-Glycosyl Hydrolases / deficiency
  • N-Glycosyl Hydrolases / genetics
  • N-Glycosyl Hydrolases / metabolism
  • Phenotype
  • Sequence Analysis, DNA
  • Somatic Hypermutation, Immunoglobulin / genetics*
  • Uracil-DNA Glycosidase


  • DNA, Bacterial
  • DNA
  • DNA-Directed RNA Polymerases
  • RNA polymerase beta subunit
  • DNA Glycosylases
  • N-Glycosyl Hydrolases
  • Uracil-DNA Glycosidase
  • AICDA (activation-induced cytidine deaminase)
  • Cytidine Deaminase