Evolution of introns and exons of class II major histocompatibility complex genes of vertebrates.

The phylogenetic relationships and patterns of nucleotide substitution were compared for introns and exons of class II major histocompatibility complex (MHC) genes in three datasets: human DRB1, human DQA1, and cyprinid fish DAB1. In both human DRB1 and cyprinid DAB1, there was strong evidence that recombination events between alleles have occurred in such a way that intron and exon sequences of a given allele do not necessarily share the same evolutionary history. In the case of human DRB1, recombination was found to have homogenized intron 1 and intron 2 sequences relative to exon 2 sequences within lineages of alleles but not between lineages. As a result, mean divergence times of intron sequences are much more recent than those of exonic sequences. Thus, the divergence time of DRB1 introns cannot be used to date that of exons in the same alleles, and the hypothesis that most human DRB1 polymorphism is of very recent origin is not supported.