MUTATIONS IN IG V(D)J GENES ARE DISTRIBUTED ASYMMETRICALLY AND INDEPENDENTLY OF THE POSITION OF V(D)J

To study the distribution of somatic mutations in the DNA flanking the 5' side of rearranged Ig V genes, the 5' region of 14 to 21 mutant fo rms of three different V(D)J were sequenced. These were compared with a fourth V(D)J for which the flanking sequences of 10 mutant forms are known. The leader intron of these four V genes varied from 82 to 365 nucleotides in length. Analysis of the data showed that: 1) The mutati on frequency is distributed asymmetrically with respect to the V(D)J e xon with skewing in the 3' direction. 2) The distribution of mutations 5' of V(D)J seems to be related to the size of the leader intron. The significance of these findings for models of hypermutation is discuss ed.