The targeting of somatic hypermutation closely resembles that of meiotic mutation

We have compared the microsequence specificity of mutations introduced duri ng somatic hypermutation (SH) and those introduced meiotically during neutr al evolution. We have minimized the effects of selection by studying nonpro ductive thence unselected) Ig V region genes for somatic mutations and proc essed pseudogenes for meiotic mutations. We find that the two sets of patte rns are very similar: the mutabilities of nucleotide triplets are positivel y correlated between the somatic and meiotic sets. The major differences th at do exist fall into three distinct categories: 1) The mutability is sharp ly higher at CG dinucleotides under meiotic but not somatic mutation. 2) Th e complementary triplets AGC and GCT are much more mutable under somatic th an under meiotic mutation. 3) Triplets of the form WAN (W = T or A) are uni formly more mutable under somatic than under meiotic mutation. Nevertheless , the relative mutabilities both within this set and within the SAN (S = G or C) triplets are highly correlated with those under meiotic mutation. We also find that the somatic triplet specificity is strongly symmetric under strand exchange for A/T triplets as well as for G/C triplets in spite of th e strong predominance of A over T mutations, Thus, we suggest that somatic mutation has at least two distinct components: one that specifically target s AGC/GCT triplets and another that acts as true catalysis of meiotic mutat ion.