HLA‐DRB9— Possible Remnant of an Ancient Functional DRB Subregion

Abstract

Gongora R, Figueroa F, O'Huigin C, Klein J. HLA-DRB9 -Possible Remnant of an Ancient Functional DRB Subregion. Scand J Immunol 1997;45:504-510 The DRB subregion of the HLA complex contains, in addition to the functional genes, a number of pseudogenes and gene fragments. Fourteen kilobases of DNA were sequenced from the segment upstream of the DRB9 gene fragment, as well as shorter segments from different HLA and corresponding ape haplotypes. The analysis of the sequences and restriction fragments indicates that the segment is a remnant of an ancient DRB subregion which may have been functional before the primate radiation and which later became the source of extant functional DRB genes in various primate groups, different ones in different groups. The remnant segment has remained constant in its organization for at least 4 million years. This constancy contrasts with the variability of the adjacent functional part of the DRB subregion occupied by the DRB1 and other loci. The constancy may be related to the monomorphism and evolutionary conservation of the DRA locus.

Presence of Solitary Exon 1 Sequences in the HLA-DR Region

“…However, DR8 arose by an internal deletion of a DR52-like haplotype, (GORSKI 1989), and DRl shares a common ancestry with DR51 ( SVENSSON et al 1996); a similar organization at the end of the haplotype should therefore be expected. We showed previously that the conserved segment in the HLA-DR region spans at least 15 kb, including the DRB9 locus and the S3 pseudogene (a solitary exon 1): S3 does not represent exon 1 of the original DRB9 gene (which now consists of a solitary exon 2) since the analysis of the flanking introns shows that these two exons are derived from different genes and have been brought together by recombination (GONGORA et al 1997). All known exon 1 sequences of the human DRB genes are presented in Fig.…”

“…There are five different groups of DR haplotypes in humans: DR1 (major haplotypes DRl and DRlO), containing DRBl and DRB6 loci; DR51 (haplotypes D R l 5 and DR16) with one additional locus, DRBS; DR52 (haplotypes DR3 and DRll-DR14), comprising two genes, DRBl and DRB3, and one pseudogene, DRB2; DR8 (haplotype DRS) consisting of a single functional locus, DRBl; and, finally, DR53 (haplotypes DR4, DR7, and DR9), with two genes DRBl and DRB4, and two pseudogenes, DRB7 and DRB8. All the haplotypes carry one additional pseudogene, DRB9, centromeric to DRA and consisting of a solitary exon 2 and flanking introns (MEUNIER et al 1986; GON-CORA et al 1996).We have identified one segment of conservation among human haplotypes -the segment containing the DRB9 locus 10 kb upstream of the DRA locus in an otherwise highly variable part of chromosome 6 (GONGORA et al 1997). In the DR4 haplotype, the DRB9 segment contains three copies of DRB exon 1 ( SPIES et al 1985).…”

“…We have identified one segment of conservation among human haplotypes -the segment containing the DRB9 locus 10 kb upstream of the DRA locus in an otherwise highly variable part of chromosome 6 (GONGORA et al 1997). In the DR4 haplotype, the DRB9 segment contains three copies of DRB exon 1 ( SPIES et al 1985).…”

Unravelling the architecture of Major Histocompatibility Complex class II haplotypes in rhesus macaques

“…An example of an old pseudogene is DRB9 . The HLA-DRB9 remnants consist of a single exon 2, which is flanked by its intron sequences, whereas the remaining gene segments are absent (Gongora et al 1997). A similar non-coding remnant is present in rhesus macaques, but the original intron-exon organization of the Mamu - DRB9 genes has been remained more intact (Fig.…”

Selection and Trans-Species Polymorphism of Major Histocompatibility Complex Class II Genes in the Order Crocodylia

“…In addition, the identification of only a single MHC class II α locus and at least two MHC class II β loci per species in the preliminary diversity analyses suggests that the α chain of the MHC molecule (II α ) has maintained some conservation of protein structure necessary for interactions with different polymorphic β chains (II β ). Primate species also show strong selection of MHC class II α genes ( DRA ), against any corrupt rearrangements or nonsilent mutants, in order to maintain their functional abilities to bind with all MHC class II DRB molecules available [33]–[36].…”