The nature of introns 4–6 suggests reduced lineage specificity in HLA-B alleles

Abstract

For most HLA-B alleles, coding sequences of the 3 0 part of the genes still need to be determined, and sequences of the 3 0 noncoding regions have yet to be studied systematically. In this study, we have determined the sequences of introns 4-6 in all HLA-B allelic groups, and computed nucleotide substitution rates and phylogenetic relationships. These sequences demonstrated an inconsistent pattern of intralineage specificity, intralineage diversity, and interlineage diversity that is best characterized by a patchwork pattern. Apart from phylogenetic studies about HLA diversity and diversification, the sequence data obtained in our study may prove valuable for haplotype-specific sequencing of the 3 0 part of HLA-B and for the explanation of recombination events in newly described HLA-B alleles.

The phylogenies of introns 4–7 demonstrate an inconsistent pattern between human leukocyte antigen‐C group topologies

“…Although, in their coding sequences, HLA‐C and HLA‐A evolve similarly (23), the structure of the 3′ introns of HLA‐C is clearly different from the 3′ introns of HLA‐A, where the sequence polymorphisms of the latter gene largely reflect the structure of the serologically defined families (20). Instead, the phylogenies of the HLA‐C 3′ introns resemble more closely to the structure observed in the 3′ part of the HLA‐B intron (21), thus favoring the idea of additional recombination in the 3′ part of the gene. The lack of bootstrap support is caused by the high homology of intron sequences, where the substitution of a single nucleotide may lead to the assignment to different clusters.…”

“…Based on serological cross‐reactivity and molecular phylogeny, the HLA‐A allelic groups can be divided into lineages and families (20). HLA‐B allelic groups can also be grouped into families based on serological cross‐reactivity, whereby there is only weak phylogenetic support from the 3′ intron data (21). In contrast to HLA‐A and B, HLA‐C has only been grouped into the lineages Cw*07, Cw*17, and a third lineage consisting of the remaining groups, but the latter groups have not been combined to families (17–19).…”