Phylogenetic history of hominoid DRB loci and alleles inferred from intronsequences

The evolutionary relationships among the MHC class II DRB4, DRB5 and DRB6 l oci as well as the allelic Lineages and alleles of the DRB1 locus were stud ied based on intron 1 and intron 2 sequences from humans, chimpanzee (Pan t roglodytes), bonobo (Pan paniscus) and gorilla (Gorilla gorilla). The phylo genetic trees for these sequences indicate that most of the DRB1 allelic li neages predate the separation of the hominoid species studied, consistent w ith previous analysis of the coding sequences of these lineages. However, t he intron sequence variation among alleles within DRB1 allelic lineages is very limited, consistent with the notion that the majority of the contempor ary alleles have been generated within the last 250,000 years. The clusteri ng of the DRB1 allelic lineages *08 and *12 with *03 supports a common ance stry for the DR8 and DR52 haplotypes. Similarly, the clustering of DRB1 all elic lineages *15 and *01 with the DRB3 locus is consistent with a common a ncestry for the DR1 and DR51 haplotypes. Two cases of recombination around the second exon were observed: 1) the HLA-DRB6 locus appears to have been g enerated through a recombination between a DRB5 allele and an ancestral DRB 6 allele, and 2) the gorilla sequence Gogo-DRB1*03 appears to have been gen erated through a recombination between the DRB3 locus and an allele from th e DRB1*03 allelic Lineage. The nucleotide substitution rate of DRB introns was estimated to 0.85-1.63 x 10(-9) per site per year, based on comparisons between the most closely related sequences from different hominoid species . This estimate is similar to the substitution rate for other intronic regi ons of the primate genome.