Gene organisation determines evolution of function in the chicken MHC

Some years ago, we used our data for class I genes, proteins and peptide-bi nding specificities to develop the hypothesis that the chicken B-F/B-L regi on represents a "minimal essential MHC". In this view, the B locus contains the classical (highly expressed and polymorphic) class I alpha and class I I beta multigene families, which are reduced to one or two members, with ma ny other genes moved away or deleted from the chicken genome altogether. We found that a single dominantly expressed class I gene determines the immun e response to certain infectious pathogens, due to peptide-binding specific ity and cell-surface expression level. This stands in stark contrast to wel l-studied mammals like humans and mice, in which every haplotype is more-or -less responsive to every pathogen and vaccine, presumably due to the multi gene family of MHC molecules present. In order to approach the basis for a single dominantly expressed class I molecule, we have sequenced a portion o f 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 com pact and simple, with many of the genes expected from the MHC of mammals ab sent, 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 diffe rently from mammals, with the TAPs in between the class I genes, the tapasi n 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 dri ve the use of a single dominantly expressed class I molecule with peptide-b inding 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. Fi nally, the presence of the C4 gene outside of the classical class I alpha a nd class II beta genes suggests the possibility that this organisation was ancestral, although a number of models of organisation and evolution are st ill possible, given the presence of the Rfp-Y region with non-classical cla ss I alpha and class II beta genes as well as the presence of multigene fam ilies of B-G and rRNA genes.