The chicken BF1 (classical MHC class I) gene shows evidence of selection for diversity in expression and in promoter and signal peptide regions

Abstract

The chicken MHC B contains two classical class I genes, BF1 and BF2, with the exception of two related haplotypes lacking BF1 due to insertion/rearrangement. In light of functional specialization of BF1 and BF2 molecules, we were interested in evaluating their relative expression at the mRNA level. We evaluated several MHC haplotypes for class I gene expression by RT-quantitative PCR. BF1 transcript levels were approximately two- to fivefold lower than BF2, with the exception of one haplotype in which BF1 expression was very low. To investigate molecular explanations for differences in BF locus or allele expression, we determined nucleotide sequences of Enhancer A and proximal promoter elements of nine different BF1 alleles, as well as their signal peptide sequences. Results showed that all BF1 alleles exhibit conservation of most of the identified promoter elements, but divergence from the Enhancer A sequence identified in the more highly expressed BF2 locus. Nonetheless, extensive BF1 allelic polymorphism was found in the promoter region and in the signal peptide, with two strongly separated allelic lineages identified for both. Patterns of promoter lineages, signal peptide lineages, and exon 2 mature protein coding sequences in individual BF1 alleles suggest that recombination among these elements has contributed to diversification of BF1 alleles. Finally, identification of a novel inactivating mutation in one BF1 allele suggests past selective pressure to eliminate BF1 function.

Expression profiles of genes within a subregion of chicken major histocompatibility complex B in spleen after Marek’s disease virus infection

“…Thus, MD continues to be a serious threat to the health of poultry. Recently, there has been a focusing on MD resistance of chickens and involved are several genetic loci including the MHC (Dalgaard et al, 2003(Dalgaard et al, , 2005Shaw et al, 2007;Shiina et al, 2007;O'Neill et al, 2009).…”

The Minor MHC Class I Gene UDA of Ducks Is Regulated by Let-7 MicroRNA

“…In humans, HLA-C has relatively limited polymorphism and lower surface expression (74,75). Likewise, BF1 alleles are less polymorphic and have a lower expression (21,26,73). Ewald and colleagues (73,76) suggested a conserved motif in the peptide binding a1 domain of BF1 alleles, which resembles the site of HLA-C interaction with killer cell Ig-like receptors (KIRs) on NK cells.…”

“…This has been clearly demonstrated in the MHC of chicken, where TAP1 and TAP2 are flanked by two classical class I genes, BF2 and BF1. BF2 is predominantly expressed and has the ligand specificity coordinated with the loading specificity of TAP2 (25), whereas BF1 is expressed at a much lower level and has a different peptide-binding specificity (8,21,26). Alternatively, BF1 has been suggested to serve as the NK cell receptor akin to HLA-C in humans (73).…”

“…Putative NK cell receptors are the chicken Iglike receptors (CHIRs) (77); however, the corresponding interaction of any CHIR with class I MHC molecules has not been established (78). Also, arguing against this fundamental role are chicken haplotypes that lack BF1 (21,26), although haplotypes with and without MHC-C and coevolving KIR alleles similarly exist in orangutans (79,80). The confirmed UDA allele, UDA*04, preserves the anchor residues necessary for peptide binding (16), suggesting it is a classical MHC class I molecule.…”

“…Additional MHC class I genes are then subject to inactivation. The poorly expressed BF1 gene had various defects that are different for each haplotype (21,26), including deletion of the NF-kB binding site, deletion of the transcription start site, and insertions or rearrangements that inactivate the gene. In contrast, TAP proteins in mammals are monomorphic (27,28) and do not have any bias in translocating peptides.…”