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Genome Biologyvolume 3, Article number: spotlight-20020618-01 (2002)
Somatic hypermutation, gene conversion and class-switch recombination are genetic rearrangements that generate the molecular diversity of immunoglobulin genes underlying the human immune system. In the June 14 Science, Yoshikawa et al. report that a single enzyme, activation-induced cytidine deaminase (AID), is sufficient to generate somatic hypermutation in fibroblasts cells (Science 2002, 296:2033-2036). To examine hypermutation, they created an NIH3T3 fibroblast cell line expressing a tetracycline-regulated mutant green fluorescent protein (GFP) gene containing a premature stop codon. They were able to select GFP-positive cells (around 1-1.8% of cells) following introduction of functional AID, but not an inactive AID isoform. The mutation rate increased with the level of transcriptional induction of GFP. Yoshikawa et al. found large numbers of mutations in the GFPgene when the target gene was transcribed (4.5 x 10-4 mutations per base pair per generation). The type of AID-induced mutations resembled those of somatic hypermutation of immunoglobulin genes.