Evidence that polymorphism in the murine major histocompatibility complex may be generated by the assortment of subgene sequences.
The high degree of polymorphism found among the class I genes of the murine major histocompatibility complex (H-2) has led to the postulation that specific genetic mechanisms are responsible for their diversity. These same genetic mechanisms are probably responsible for the high spontaneous mutation frequency seen in H-2 alleles. The bml mutation of the H-2Kb gene has been shown to be 7 base pair changes over a 13 base pair region that result in three amino acid substitutions in the C1 domain of the protein product. The clustering of base-pair changes has suggested that the bm1 mutation resulted from a recombinational event analogous to gene conversion between the H-2Kb gene and a "donor" gene sequence. A 23-base oligonucleotide complementary to the bm1 mutant sequences was synthesized and used to probe genomic DNA restriction digests of the parental H-2b haplotype as well as other H-2 haplotypes. Our results indicate that a potential donor gene sequence is present in the genomes of all of the five mouse strains studied. Of eight tissues that were tested by blot-hybridization analysis, the potential donor gene sequences are transcribed only in the liver. Models for the generation of polymorphism among the H-2 class I genes via subgene rearrangements are proposed.
Miyada
C G
CG
Klofelt
C
C
Reyes
A A
AA
McLaughlin-Taylor
E
E
Wallace
R B
RB
D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D005785:Gene Conversion; D014644:Genetic Variation; D006183:H-2 Antigens / Q000235:genetics*; D008285:Major Histocompatibility Complex; D051379:Mice; D008815:Mice, Inbred Strains; D009154:Mutation; D011110:Polymorphism, Genetic; D012313:RNA / Q000235:genetics; D011995:Recombination, Genetic
D006183:H-2 Antigens; D012313:RNA; D004247:DNA