The DNA sequence of the H-2kb gene: evidence for gene conversion as a mechanism for the generation of polymorphism in histocompatibilty antigens.

Abstract

We have determined the DNA sequence of the H-2Kb gene of the C57B1/10 mouse. Comparison of this sequence with that of the allelic H-2Kd shows surprisingly that the exons have accumulated more mutations than their introns. Moreover, many of these changes in the exons are clustered in short regions or hot spots. Additional comparison of these sequences with the H-2Ld and H-2Db sequences shows that, in several cases, the altered sequence generated at the hot spot is identical to the corresponding region of a non-allelic H-2 gene. The clustered changes are responsible for 60wo of the amino acid differences between the H-2Kb and H-2Kd genes and suggest that micro-gene conversion events occurring within the exons and involving only tens of nucleotides are an important mechanism for the generation of polymorphic differences between natural H-2 alleles.

Molecular biology of the mouse Q region

“…6). At the 3' end, the genes are virtually identical and display a similar degree of homology as the H-2K alleles [23]. A more impressive example is found in the Q7 and Q9 genes.…”

“…This finding and the presence of a class I multigene family in the genome led to the speculation that a gene conversion-like mechanism may be responsible for the generation of diversity in H-2 genes. It was proposed that blocks of nucleotides circulate within genes by this nonreciprocal process [23,[27][28][29][30][31]. It seemed reasonable that polymorphism is a direct result of the mechanism introducing mutations in the H-2K gene.…”

Sequence of the mouse Q4 class I gene and characterization of the gene product

“…T~C T~~~ 3887 Nucleotide sequence data were obtained from the following sources: H-2K b, Weiss et al 1983; H-2D d, Taylor Sher et al 1985; QT, Q8, Devlin et al 1985; QIO, Mellor et al 1984 hancer element is composed of two overlapping 18 bp repeats, only one copy of which is found in Q4.…”

“…Since no Q4 cDNA clones have been isolated so far, the boundaries of the protein-coding exons of Q4 were assigned using consensus splice-donor and acceptor sequences, as well as by comparison with the H-2I( ° gene (Weiss et al 1983). Thus the regions marked in triplets near the bottom of Figure 2 correspond to exons 6, 7, and 8 and the 3' untranslated region of H-2I( °.…”

“…Comparisons among other genes in Table 1 have been published elsewhere (Weiss et al 1983, Devlin et al 1985, Arnold et al 1984). …”