Gene organisation determines evolution of function in the chicken MHC

Abstract

Some years ago, we used our data for class I genes, proteins and peptide-binding specificities to develop the hypothesis that the chicken B-F/B-L region represents a "minimal essential MHC". In this view, the B locus contains the classical (highly expressed and polymorphic) class I alpha and class II beta multigene families, which are reduced to one or two members, with many other genes moved away or deleted from the chicken genome altogether. We found that a single dominantly expressed class I gene determines the immune response to certain infectious pathogens, due to peptide-binding specificity and cell-surface expression level. This stands in stark contrast to well-studied mammals like humans and mice, in which every haplotype is more-or-less responsive to every pathogen and vaccine, presumably due to the multigene family of MHC molecules present. In order to approach the basis for a single dominantly expressed class I molecule, we have sequenced a portion of the B complex and examined the location and polymorphism of the class I (B-F) alpha, TAP and class II (B-L) beta genes. The region is remarkably compact and simple, with many of the genes expected from the MHC of mammals absent, including LMP, class II alpha and DO genes as well as most class III region genes. However, unexpected genes were present, including tapasin and putative natural killer receptor genes. The region is also organised differently from mammals, with the TAPs in between the class I genes, the tapasin gene in between the class II (B-L) beta genes, and the C4 gene outside of the class I alpha and class II beta genes. The close proximity of TAP and class I alpha genes leads to the possibility of co-evolution, which can drive the use of a single dominantly expressed class I molecule with peptide-binding specificity like the TAP molecule. There is also a single dominantly expressed class II beta gene, but the reason for this is not yet clear. Finally, the presence of the C4 gene outside of the classical class I alpha and class II beta genes suggests the possibility that this organisation was ancestral, although a number of models of organisation and evolution are still possible, given the presence of the Rfp-Y region with non-classical class I alpha and class II beta genes as well as the presence of multigene families of B-G and rRNA genes.

Unprecedented Polymorphism of Mhc-DRB Region Configurations in Rhesus Macaques

“…This has been documented for common marmosets, a New World monkey from the neotropical rain forests (32). In addition, the chicken has been reported to possess a "minimal essential Mhc" with two class II genes (43). These examples illustrate that evolutionary strategies for a functional Mhc-DR region are different between distinct species.…”

Different Evolutionary Histories of the Two Classical Class I Genes BF1 and BF2 Illustrate Drift and Selection within the Stable MHC Haplotypes of Chickens

“…Livant et al (44) analyzed exon 2 to exon 3 genomic sequences from 16 MHC haplotypes from broiler lines and conclude that there are two groups of sequences, one of which has fewer alleles, lower diversity, and much less selection than the other. They propose that the poorly selected sequences are derived from the BF1 gene, based on our previous work (7,8), and suggest that this gene is involved in recognition by NK cells, based on a motif in the ␣ helix of the ␣1 domain which in mammals is implicated in recognition by killer Ig receptors. Chickens have recently been shown to have a large family of KIR genes in the leukocyte receptor complex (45,46).…”

“…Among the genetic loci potentially involved in the immune response, the chicken MHC can determine decisive resistance and susceptibility to several infectious pathogens, as well as the response to both live and killed commercial vaccines (1)(2)(3)(4). Compared with typical mammals such as humans and mice, the chicken MHC is simpler, smaller, and rearranged (5)(6)(7)(8). Based on these data, we developed the concept of a "minimal essential MHC" to give a molecular basis to the striking functional properties of the chicken MHC (7)(8)(9).…”

“…As a hypothesis to explain why only one of the two class I genes is expressed at a high level, we proposed coevolution of the class I genes with other MHC genes (such as the TAP genes) involved in peptide loading (7,8,13). Such coevolution requires close genetic linkage (13)(14)(15) and, in fact, no recombination between the serologically defined class I and class II B genes has been observed in thousands of experimental matings (16 -19).…”

Extensive Allelic Diversity of MHC Class I in Wild Mallard Ducks

“…The MHC is made up of two clusters, the B locus (8) and the Rfp-Y locus (9). The B locus carries all the genes essential for the function of the MHC, determining tissue allograft rejection, MLRs, and cellular cooperation for Ab production and encoding MHC class I and class II (10,11), and thus was named a "minimal essential MHC" (12). Within the B cluster, two MHC class I genes flank either side of TAP1 and TAP2, and of these, the BF2 gene adjacent to TAP2 is predominantly expressed.…”