Locus specificity of polymorphic alleles and evolution by a birth-and-death process in mammalian MHC genes

We have conducted an extensive phylogenetic analysis of polymorphic alleles from human and mouse major histocompatibility complex (MHC) class I and cl ass II genes. The phylogenetic tree obtained for 212 complete human class I allele sequences (HLA-A, -B, and -C) has shown that all alleles from the s ame locus form a single cluster which is highly supported by bootstrap valu es, except for one HLA-B allele (HLA-B*7301). Mouse MHC class I loci did no t show locus-specific clusters of polymorphic alleles. This was considered to be because of either interlocus genetic exchange or the confusing design ation of loci in different haplotypes at the present time. The locus specif icity of polymorphic alleles was also observed in human and mouse MHC class II loci. It was therefore concluded that interlocus recombination or gene conversion is not very important for generating MHC diversity, with a possi ble exception of mouse class I loci. According to the phylogenetic trees of complete coding sequences, we classified human MHC class I (HLA-A, -B, and -C) and class II (DRB1) alleles into three to five major allelic lineages (groups), which were monophyletic with high bootstrap values. Most of these allelic groups remained unchanged even in phylogenetic trees based on indi vidual exons, though this does not exclude the possibility of intralocus re combination involving short DNA segments. These results together with the p revious observation that MHC loci are subject to frequent duplication and d eletion, as well as to balancing selection, indicate that MHC evolution in mammals is in agreement with the birth-and-death model of evolution, rather than with the model of concerted evolution.