Structure of class II genes in wild mouse Mus saxicola: functional and evolutionary implications

Class II beta genes have been characterized from Mus saxicola, a wild mouse which diverged five millions years ago from the house mouse. The nucleotide sequences of the exons 2 and 3 of E beta 1, A beta 2 and E beta 2 genes have been determined in order to define the molecular mechanisms of interspecies variability. The E beta 1 and A beta 1 (J. X. She, personal communication) genes from Mus saxicola display extensive sequence variability in exon 2 when compared to those of the house mouse, in association with the variability of residues probably involved in antigen binding. On the other hand, most putative T cell contact residues from the I-E beta chain, and to a lesser extent from the I-A beta chain, were found conserved in mice. T cell contact residues from Mus saxicola I-A beta and I-E beta chains are identical to those of the b and q, and of the k haplotypes of the house mouse, respectively. Comparisons performed with A beta 2 and E beta 2 genes revealed that both are highly conserved and, in contrast to A beta 1 and E beta 1 genes, that a strong selective pressure for conservation occurs in the A beta 2 second exon. The different aspects of A beta 2 and E beta 2 genes evolution may correlate with the original function of their products. Comparisons of the intervening sequences revealed that the repeated motifs of the hotspot region present in the E beta 1b gene are also conserved in Mus saxicola. Recombinations may have occurred, in some cases in association with chi-like sequences.