Abstract
The recent availability of genomic sequences within the human Major Histocompatibility Complex (MHC) has allowed a detailed study of its organisation, gene content and nucleotide diversity. The MHC is characterised by polymorphic multicopy gene families including the Human Leucocyte Antigens (HLA) Class 1 and Il genes (Geraghty ct al. 1992), large kilobase insertions and deletions (indels) (Venditti and Chorney 1992; Watanabe et al. 1997), and uneven rates of recombination (Carrington 1999). Balancing selection has been reported to operate on the antigen presenting HLA Class I genes (Hughes and Nei 1988), with elevated silent differences at linked neutral sites attributed to a hitch-hiking effect (Grimsley et al. 1998, Horton et al. 1998; Satta et al. 1998). To examine the extent of nucleotide diversity at non-HLA Class I loci, we compared different human haplotypes in 380 lib of sequence from ikBL to telomeric of HLA-C, including HLA-B. We show that the level of nucleotide diversity within the MHC is several fold greater than elsewhere in the genome with peaks not always corresponding to the HLA Class loci. This unusually high level of nucleotide diversity is contained within a region of the MHC described as a polymorphic frozen block (PFB) (beta block). A region associated with limited meiotic recombination and high non-coding nucleotide diversity. A hitch-hiking effect from balancing selection operating on the HLA Class I genes is likely to be contributing to the nucleotide diversity pattern within the MHC, however, other evolutionary processes such as duplications and indels also appear to play an important role.