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Publication : Spontaneous H-2 mutants provide evidence that a copy mechanism analogous to gene conversion generates polymorphism in the major histocompatibility complex.

First Author  Pease LR Year  1983
Journal  Proc Natl Acad Sci U S A Volume  80
Issue  1 Pages  242-6
PubMed ID  6571997 Mgi Jnum  J:109263
Mgi Id  MGI:3628619 Doi  10.1073/pnas.80.1.242
Citation  Pease LR, et al. (1983) Spontaneous H-2 mutants provide evidence that a copy mechanism analogous to gene conversion generates polymorphism in the major histocompatibility complex. Proc Natl Acad Sci U S A 80(1):242-6
abstractText  The analysis of H-2K products from spontaneously generated major histocompatibility complex (MHC) mutants and of the primary structure of other class I antigens suggests the genetic hypothesis that diversity in the MHC results from a copy mechanism analogous to gene conversion. The hypothesis was tested by making precise structural predictions about three partially characterized MHC mutants (bm1, bm3, and bm8). The predictions were based on consensus sequences among class I genes that differ from H-2Kb in the same region of the molecule as do the Kb mutants. In two cases (bm3 and bm8) we successfully predicted the correct amino acid substitution at positions known to be altered but for which the specific nature of the substitution had not been determined. In two additional cases (bm1 and bm8) we predicted and found both new mutation sites and the specific amino acid substitutions. The positions and identifications of the variant amino acids were determined by radiolabeled amino acid sequence analysis and DNA restriction endonuclease analysis. The interaction of MHC genes through a copy mechanism to generate diversity permits the introduction of multiple nucleotide base substitutions into class I sequences by a single genetic event. Such a mechanism may account in part for the large structural divergence among alleles of MHC loci and the high degree of MHC polymorphism among wild mice.
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