The HLA-AW24 gene: sequence, surroundings and comparison with the HLA-A2 and HLA-A3 genes

A cosmid clone containing two class I sequences was found to cause expression of the HLA-AW24 protein after transfection into mouse L cells. The restriction map of this cosmid shows extensive homology over 26 kb with the map of the HLA-A3 region obtained from cosmids of the same library, constructed with DNA from an HLA-A3/HLA-AW24 heterozygote, but diverges over the remaining 14 kb. The HLA-AW24 gene was subcloned from this cosmid and its nucleotide sequence was determined. Amino acid and, more strikingly, nucleotide sequence comparisons with other HLA alleles indicate that the A locus alleles are more closely related to each other than to alleles from other HLA loci. A very skewed distribution of silent substitutions is apparent, and the occurrence of clustered multiple substitutions hints at gene-conversion-like events.