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Vol. 10, Issue 10, 1579-1586, October 2000

LETTER
SNP Profile within the Human Major Histocompatibility Complex Reveals an Extreme and Interrupted Level of Nucleotide Diversity

Silvana Gaudieri,1,2 Roger L. Dawkins,2 Kaori Habara,1 Jerzy K. Kulski,2 and Takashi Gojobori1,3

1 Center for Information Biology, National Institute of Genetics, Mishima, Shizuoka-ken 411-8540, Japan; 2 Centre for Molecular Immunology and Instrumentation, University of Western Australia, Nedlands 6008, Western Australia, Australia

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

[The sequence data for the multiple haplotype comparisons within the class I region have been submitted to DDBJ/EMBL/GenBank under accession nos. AF029061, AF029062, and AB031005-AB031010. Additional sequence data have been submitted to the DDBJ data library under accession nos. AB031005-AB03101 and AF029061-AF029062.]

3 Corresponding author.

10:1579-1586 ©2000 by Cold Spring Harbor Laboratory Press  ISSN 1088-9051/00 $5.00
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