The I region of the C57BL/10 mouse: characterization and physical linkage to H-2K of an SB beta-like class II pseudogene, psi A beta 3

Abstract

In the C57BL/10 mouse, 140 kilobases (kb) of the I region (I-Ab, I-Eb) were isolated as recombinant cosmids. The class II genes A beta 2, A beta 1, A alpha,E beta 1, E beta 2, and E alpha are located from centromere to telomere in a region of approximately equal to 110 kb, which shows that the I region in the b haplotype has a similar overall organization to those described for the d, k, and wr7 haplotypes. In addition to these genes, we have also isolated a class II gene, psi A beta 3, which is physically linked to the class I H-2K region, 75 kb telomeric to the H-2Kb gene. This orients the H-2K region on the genetic map with the H-2Kb gene being located toward the I region. The sequence of the beta 2 domain of psi A beta 3 is similar to the immunoglobulin-like domain of other class II genes. Interestingly, it shows 83% nucleotide homology to the human SB beta gene, the same homology that was seen previously between the immunoglobulin-like exons of A beta 1 and DC beta and between E beta 1 and DR beta, respectively. It is likely, therefore, that psi A beta 3 represents a member of a third SB-like class II gene family present in addition to I-A and I-E genes and that the divergence of the SB family predates the speciation of rodents and primates. Comparison of the DNA sequence of the exon encoding the beta 2 domain of psi A beta 3 in the b or k haplotypes with functional class II genes shows that a deletion of eight nucleotides has occurred, such that the psi A beta 3 sequence cannot be translated into a functional class II protein. This suggests that psi A beta 3 is a pseudogene.