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*
Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545;
Department of Immunology, Duke University Medical Center, Durham, NC 27710; and
The Santa Fe Institute, Santa Fe, NM 87501
We have compared the microsequence specificity of mutations introduced during somatic hypermutation (SH) and those introduced meiotically during neutral evolution. We have minimized the effects of selection by studying nonproductive (hence unselected) Ig V region genes for somatic mutations and processed pseudogenes for meiotic mutations. We find that the two sets of patterns are very similar: the mutabilities of nucleotide triplets are positively correlated between the somatic and meiotic sets. The major differences that do exist fall into three distinct categories: 1) The mutability is sharply higher at CG dinucleotides under meiotic but not somatic mutation. 2) The complementary triplets AGC and GCT are much more mutable under somatic than under meiotic mutation. 3) Triplets of the form WAN (W = T or A) are uniformly 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 the strong predominance of A over T mutations. Thus, we suggest that somatic mutation has at least two distinct components: one that specifically targets AGC/GCT triplets and another that acts as true catalysis of meiotic mutation.
This article has been cited by other articles:
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  U. Hershberg, M. Uduman, M. J. Shlomchik, and S. H. Kleinstein Improved methods for detecting selection by mutation analysis of Ig V region sequences Int. Immunol., May 1, 2008; 20(5): 683 - 694. [Abstract] [Full Text] [PDF]
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I. B. Rogozin and M. Diaz Cutting Edge: DGYW/WRCH Is a Better Predictor of Mutability at G:C Bases in Ig Hypermutation Than the Widely Accepted RGYW/WRCY Motif and Probably Reflects a Two-Step Activation-Induced Cytidine Deaminase-Triggered Process J. Immunol., March 15, 2004; 172(6): 3382 - 3384. [Abstract] [Full Text] [PDF]
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Y. I. Pavlov, I. B. Rogozin, A. P. Galkin, A. Y. Aksenova, F. Hanaoka, C. Rada, and T. A. Kunkel Correlation of somatic hypermutation specificity and A-T base pair substitution errors by DNA polymerase eta during copying of a mouse immunoglobulin kappa light chain transgene PNAS, July 23, 2002; 99(15): 9954 - 9959. [Abstract] [Full Text] [PDF]
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