AMINO-ACID INSERTIONS AND DELETIONS CONTRIBUTE TO DIVERSIFY THE HUMANIG REPERTOIRE

The sequence analysis of Ig variable region genes transcribed within d ifferent B-cell subpopulations from human tonsil led us to identify a rare DNA sequence modification event consisting of bp insertions and/o r deletions (I/D). Although these events were previously reported, the y had never been formally associated with the somatic hypermutation pr ocess. I/D events share with more conventional somatic hypermutation e vents their localization within hypervariable regions and, most partic ularly, within DNA motifs known to be mutational hot spots. Repetitive DNA tracts or DNA elements capable of forming DNA loop intermediates seem to be the preferred substrate for I/D to occur. These characteris tics suggest a model for somatic hypermutation reminiscent of the ''po lymerase slippage'' model involved in replication and repair mutations in prokaryotes, yeast, and mammals.