Sequence of a Complete Chicken BG Haplotype Shows Dynamic Expansion and Contraction of Two Gene Lineages with Particular Expression Patterns

Abstract

Many genes important in immunity are found as multigene families. The butyrophilin genes are members of the B7 family, playing diverse roles in co-regulation and perhaps in antigen presentation. In humans, a fixed number of butyrophilin genes are found in and around the major histocompatibility complex (MHC), and show striking association with particular autoimmune diseases. In chickens, BG genes encode homologues with somewhat different domain organisation. Only a few BG genes have been characterised, one involved in actin-myosin interaction in the intestinal brush border, and another implicated in resistance to viral diseases. We characterise all BG genes in B12 chickens, finding a multigene family organised as tandem repeats in the BG region outside the MHC, a single gene in the MHC (the BF-BL region), and another single gene on a different chromosome. There is a precise cell and tissue expression for each gene, but overall there are two kinds, those expressed by haemopoietic cells and those expressed in tissues (presumably non-haemopoietic cells), correlating with two different kinds of promoters and 5′ untranslated regions (5′UTR). However, the multigene family in the BG region contains many hybrid genes, suggesting recombination and/or deletion as major evolutionary forces. We identify BG genes in the chicken whole genome shotgun sequence, as well as by comparison to other haplotypes by fibre fluorescence in situ hybridisation, confirming dynamic expansion and contraction within the BG region. Thus, the BG genes in chickens are undergoing much more rapid evolution compared to their homologues in mammals, for reasons yet to be understood.

Regulation of Immunity by Butyrophilins

“…BG gene clusters show structural complexity among haplotypes that is indicative of dynamic expansion and contraction with the production of polymorphic hybrid genes. These features are reminiscent of the structural variation observed at the mouse Skint locus and are consistent with selection and rapid evolution (128). BG proteins are disulfide-linked dimers composed of a single extracellular butyrophilin-like IgV domain, a single transmembrane region, and a cytoplasmic tail of variable length, with the notable absence of a B30.2 domain.…”

“…BG proteins are disulfide-linked dimers composed of a single extracellular butyrophilin-like IgV domain, a single transmembrane region, and a cytoplasmic tail of variable length, with the notable absence of a B30.2 domain. BG molecules showed complex expression in tissues (128) and have been linked to the selection of B cells (129). Preferential antibody responses have been generated toward minor protein fractions in mixed immunization with BG molecules, which is characteristic of an adjuvant effect (130).…”

A New Chicken Genome Assembly Provides Insight into Avian Genome Structure

“…Given the highly polymorphic nature of the region (Fulton et al 2016) and the known immune function of many of the genes, accurate and complete genome assembly is important for continued studies of immunity in avian diseases. Assembly of GGA16 has advanced in Gallus_gallus-5.0 and is now supporting the emerging picture that some segments of GGA16 are subject to gene copy number variation (Afanassieff et al 2001; Salomonsen et al 2014; Fulton et al 2016). However, more complete MHC and other immune system genes sequence representation are needed to further advance our knowledge of immune response.…”

Surface expression, peptide repertoire, and thermostability of chicken class I molecules correlate with peptide transporter specificity

“…1 and 4 and Fig. S1), as described (10,18,29,30). F1 families based on H.B15 and H.B21b chickens led to B15/B21 progeny at the Gipf (Oberfrick) Farm of the Basel Institute for Immunology (Fig.…”