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. 2006 May;2(5):e73.
doi: 10.1371/journal.pgen.0020073. Epub 2006 May 12.

The leukocyte receptor complex in chicken is characterized by massive expansion and diversification of immunoglobulin-like Loci

Katja Laun  1 , Penny Coggill, Sophie Palmer, Sarah Sims, Zemin Ning, Jiannis Ragoussis, Emanuela Volpi, Natalie Wilson, Stephan Beck, Andreas Ziegler, Armin Volz
Affiliations

The leukocyte receptor complex in chicken is characterized by massive expansion and diversification of immunoglobulin-like Loci

Katja Laun et al. PLoS Genet. 2006 May.

Abstract

The innate and adaptive immune systems of vertebrates possess complementary, but intertwined functions within immune responses. Receptors of the mammalian innate immune system play an essential role in the detection of infected or transformed cells and are vital for the initiation and regulation of a full adaptive immune response. The genes for several of these receptors are clustered within the leukocyte receptor complex (LRC). The purpose of this study was to carry out a detailed analysis of the chicken (Gallus gallus domesticus) LRC. Bacterial artificial chromosomes containing genes related to mammalian leukocyte immunoglobulin-like receptors were identified in a chicken genomic library and shown to map to a single microchromosome. Sequencing revealed 103 chicken immunoglobulin-like receptor (CHIR) loci (22 inhibitory, 25 activating, 15 bifunctional, and 41 pseudogenes). A very complex splicing pattern was found using transcript analyses and seven hypervariable regions were detected in the external CHIR domains. Phylogenetic and genomic analysis showed that CHIR genes evolved mainly by block duplications from an ancestral inhibitory receptor locus, with transformation into activating receptors occurring more than once. Evolutionary selection pressure has led not only to an exceptional expansion of the CHIR cluster but also to a dramatic diversification of CHIR loci and haplotypes. This indicates that CHIRs have the potential to complement the adaptive immune system in fighting pathogens.

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Conflict of interest statement

Competing interests. The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Chromosome Mapping of the Chicken LRC
Dual-color FISH on chicken chromosome preparations showing colocalization of BACs 7H19 (red) and 93H17 (green) on metaphase (main picture) and interphase (inset). The clones map to a microchromosome, most likely belonging to group C (according to the chicken chromosome classification system proposed by [64]). The MHC-harboring BAC 65G09 did not colocalize to the same microchromosome (results not shown).
Figure 2
Figure 2. Genomic Organization of the Chicken LRC
Gray boxes (top) represent the finished and submitted sequences of the corresponding BACs. White boxes represent the unfinished sequence overlaps between BACs that were analyzed but clipped to 2 kb as part of the submission process. All other tracks are labeled individually. Gene symbols are purple for CHIRs with two Ig-domains and yellow for one Ig-domain CHIRs, with the transcriptional orientation depicted by an arrowhead. Pseudogenes which were erroneously described by Nikoloaidis and colleagues [23] as functional are displayed in orange; all others are gray. Regions homologous to single CHIR exon/introns are presented as boxes with the following relation to the respective gray area: exon A above, exon B intersecting at the top, exon 1 at the top, exons 2 to 6 descending to exon 7 at the bottom, and exon C intersecting at the bottom. Intergenic regions labeled “Orig” were used to detect the respective homologous regions labeled by the same color. Duplication blocks are presented as arrows colored according to the enclosed intergenic regions. Note letters at the line “EST-homologies” and their specification in Table 3. A high-resolution version of Figure 2 is available as supporting material at http://www.charite.de/immungenetik/CHIR.
Figure 3
Figure 3. Examples of Alternative Splicing Found in CHIR Transcripts
At the left are the accession numbers of the given examples. Spliced introns with correct splice donors and acceptors are displayed as single dotted lines. If splice sites do not meet the consensus sequences, introns are displayed as hatched lines. Introns not removed are presented as gray lines. The exon at the 3′ end of CF252231 shows only extremely weak homology to CHIR genes and was therefore colored gray. AAAAA indicates that the respective transcript contains a polyA tail.
Figure 4
Figure 4. Tissue Distribution of Differentially Spliced CHIR Transcripts
The figure gives the relative frequency of a given type of transcript within a tissue. Below the columns, the numbers of CHIR transcripts found and the total number of ESTs available for the respective tissues are specified. Tissues providing less than six CHIR transcripts, as, e.g., kidney or leg muscle, are combined in “others.” This figure represents no tissue specific expression analysis, since ESTs from different genes were subsumed. Additionally, ESTs of most tissues were derived from several different libraries of which some have been normalized, making a direct comparison meaningless [25].
Figure 5
Figure 5. Variability of CHIR Genes
The area shaded in light gray in the upper part of the figure demonstrates nonsynonymous exchange rates calculated for each codon and all pairwise comparisons of the 62 potentially functional CHIR genes according to the scale on the left. The overlaid black bars delineate the respective amino acid-based Wu-Kabat [26] values according to the scale on the right. Bars of conserved cysteines are marked with a black arrowhead and bars of ITIM tyrosines are marked with a white arrowhead. The gray area in the lower part of the figure shows the respective synonymous exchanges. Between the two plots, the domain structure and the numbering of amino acids of the immature (bottom) and the mature protein (top) are given.
Figure 6
Figure 6. Phylogenetic Tree of CHIR Genes
The presented tree was calculated by Phylowin with exon 5 sequences and the following parameters: Neighbor joining with pairwise gap removal, Kimura distance, and 1,000 bootstrap replicates. Bootstrap values are given in gray at the major branches. CHIR2B15 was used as root, since it clusters with LILRB2 in the exon 4 tree and no sequences of other species homologous to exon5 could be detected in databases. Further trees with other topographies verified clustering of lineage 1 genes with a bootstrap value of 100 (not shown). Designations of genes were color-coded according to their status: red tones—inhibitory receptors, green tones—activating receptors, and blue tones—bifunctional receptors. To allow easy differentiation between lineages, each lineage was given a different hue. Trees corresponding to exons 2 and 3 are available at http://www.charite.de/immungenetik/CHIR.
Figure 7
Figure 7. Suggested Evolution of CHIR Genes
This hypothetical evolutionary tree for CHIR genes is largely based on phylogenetic analysis of exon 5. Evolutionary intermediates are boxed; lineage designations are according to Figure 6.
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