Ragoussis and co-workers previously described a class I HLA gene (now designated HLA-J) that maps to within 50 kb of HLA-A. The nucleotide sequences of three HLA-J alleles are reported here. Comparison of the nucleotide sequences of HLA-J alleles shows this gene is more related to HLA-G, A, and H than to HLA-B, C, E, and F. All four alleles of HLA-J are pseudogenes because of deleterious mutations that produce translation termination either in exon 2 or exon 4. Apart from these mutations. the predicted proteins have structures similar to those of HLA-A, B, and C molecules. There is, however, little polymorphism at HLA-J and none at functional positions of the Ag-recognition site. The polymorphism is less than found for HLA-H, another HLA-A-related pseudogene. HLA-J appears, like HLA-H, to be an inactivated gene that resulted from duplication of an Ag-presenting locus related to HLA-A. Nucleotide sequence comparisons show that the HLA-A, H, J, and G genes form a well defined group of [open quotes]HLA-A-related[close quotes] loci. Evolutionary relationships as assessed by construction of trees suggest the four modern loci, HLA-A, G, H, and J, were formed by successive duplications from a common ancestral gene. In this scheme one intermediate locusmore » gave rise to HLA-A and H, the other to HLA-G and J. 33 refs., 6 figs., 4 tabs.« less