Concerted evolution in a segment of the first domain exon of polymorphic MHC class II beta loci

Genetic exchange of sequence information between members of a gene family, generally denoted gene conversion, causes a phenomenon called "concerted evolution" meaning that non-allelic genes do not evolve independently. The possible significance of this phenomenon in the evolution of major histocompatibility complex (MHC) class II genes has been investigated in the present study. The results of a phylogenetic analysis of human, mouse, bovine, and chicken class II sequences were consistent with the occurrence of gene conversion between polymorphic class II beta genes (i.e. DPB, DQB, and DRB) but not between these genes and the monomorphic DOB gene or between class II alpha genes. Gene conversion between polymorphic beta genes appears to be restricted to a gene segment between approximately nucleotide positions 94-286 in the first domain exon. Due to this genetic exchange, there is a greater interlocus similarity both at the DNA and protein level in this region than in the rest of the sequence. The region encodes a functionally important part of the class II molecule including more than half of the beta-chain residues of the antigen binding site and the residues in the alpha helix assumed to form contact with the T-cell receptor. The observed similarity in the alpha-helical region of class II beta molecules may be functionally significant for the utilization of the T-cell repertoire for antigen recognition in the immune system.