Identification of two pseudogenes with sequence homology to human and gorilla MHC class IA genes: ancestral haplotype in the Filipino population

Abstract

While characterizing exons 2 and 3 of the class I human leukocyte antigen (HLA)-A locus in human lymphocytes, two similar but unexpected PCR products were detected in six samples of Filipino ethnicity. A nucleotide sequence analysis of the two amplicons, tentatively named HLA-COQ and HLA-DEL, rendered them as two novel and seemingly related sequences, both with homology to the gorilla and human major histocompatibility complex (MHC) A locus. Exon 2 is similar to the published human pseudogenes HLA-BEL, HLA-Y, and to primate MHC Gogo-A*0501, differing by 2 bp from HLA-BEL, and HLA-Y, and by 4 bp from Gogo-A*0501. Exon 3 is most similar to HLA-A*2902 and A*310102, differing by 7 bp from A*2902, and by 8 bp from A*31012. Genomic sequence comparison of exons 1 to 8 indicates that their closest published match is to the Gogo-A*0501. Complete typing at the HLA-A, -B, -C, DRB1, and DRB5 loci for the six samples yielded the reoccurring types: HLA-A*3401, -B*1521/1525, -Cw*0403, -DRB1*150201, and DRB5*010101. Thus far, HLA-COQ and HLA-DEL have been detected only in Filipino samples containing these HLA types. The HLA-COQ gene is nonfunctional based on a stop codon located in exon 4. HLA-DEL is also a nonfunctional gene because of the dual cytosine insertion in exon 4, with a reading frame shift generating a stop codon downstream. Parsimony analysis of the two pseudogenes with 31 other primate A locus coding regions resulted in a phylogenetic tree that segregated the two pseudogenes with the Gogo-A*0501, suggesting that HLA-COQ, HLA-DEL, and Gogo-A*0501 evolved from a common ancestral allele.