SNP profile within the human major histocompatibility complex reveals an extreme and interrupted level of nucleotide diversity

The human major histocompatibility complex (MHC) is characterized by polymo rphic multicopy gene families, such as HLA and MIC (PERB11); duplications; insertions and deletions (indels); and uneven rates of recombination. Polym orphisms at the antigen recognition sites of the HLA class I and II genes a nd at associated neutral sites have been attributed to balancing selection and a hitchhiking effect, respectively. We, and others, have previously sho wn that nucleotide diversity between MHC haplotypes at non-HLA sites is unu sually high (>10%) and up to several times greater than elsewhere in the ge nome (0.08%-0.2%). We report here the most extensive analysis of nucleotide diversity within a continuous sequence in the genome. We constructed a sin gle nucleotide polymorphism (SNP) profile that reveals a pattern of extreme but interrupted levels of nucleotide diversity by comparing a continuous s equence within haplotypes in three genomic subregions of the MHC. A compari son of several haplotypes within one of the genomic subregions containing t he HLA-B and -C loci suggests that positive selection is operating over the whole subgenomic region, including HLA and non-HLA genes.