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High allelic polymorphism, moderate sequence diversity and diversifying selection for B-NK but not B-lec, the pair of lectin-like receptor genes in the chicken MHC

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Abstract

We previously characterised the C-type lectin-like receptor genes B-NK and B-lec, located next to each other in opposite orientations in the chicken major histocompatibility complex (MHC). We showed that B-NK is an inhibitory receptor expressed on natural killer cells, whereas B-lec is an activation-induced receptor with a broader expression pattern. It is interesting to note that the chicken MHC has been linked with resistance or susceptibility to Marek’s disease virus (MDV), an oncogenic herpes virus. Recent reports show that the C-type lectin-like receptors in mouse and rat (Ly49H, NKR-P1 and Clr) are associated with resistance to another herpesvirus, cytomegalovirus (CMV). Therefore, B-NK and B-lec are potential candidate genes for the MHC-mediated resistance to MDV. In this paper, we report that both genes encode glycosylated type II membrane proteins that form disulphide-linked homodimers. The gene sequences from nine lines of domestic chicken representing seven haplotypes show that B-lec is well conserved between the different haplotypes, apparently under purifying selection. In contrast, B-NK has high allelic polymorphism and moderate sequence diversity, with 21 nucleotide changes in the complementary deoxyribonucleic acids (cDNAs) resulting in 20 amino acid substitutions. The allelic variations include substitutions, an indel and loss/gain of three predicted N-linked glycosylation sites. Strikingly, there is as much as 7% divergence between protein sequences of B-NK from different haplotypes, greater than the difference observed between the highly polymorphic human KIR NK receptors. Analysis of ds and dn reveal evidence of strong positive selection for B-NK to be polymorphic at the protein level, and modelling demonstrates significant variation between haplotypes in the predicted ligand binding face of B-NK.

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Acknowledgements

We thank Drs. Clive Tregaskes and John Young (Institute for Animal Health) for the kind gift of pCIpac, Venugopal Nair (Institute for Animal Health) and John Trowsdale and Hugh Reyburn (University of Cambridge) for critical reading of the manuscript, F. Hoffman- La Roche & Co, Ltd. for support at the BII, and the Biotechnology and Biosciences Research council (BBSRC) for support at the IAH.

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Correspondence to Jim Kaufman.

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The nucleotide sequence data reported in this paper have been submitted to the EMBL/GenBank nucleotide sequence databases and have been assigned the accession numbers AM950189 to AM950197.

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Supplementary Table 1

Details of primers. The top section of the table refers to primers used to PCR amplify fragments of B-NK and B-lec, and the annealing temperature of the primers and the extension time used in the programme are shown. The bottom section of the table refers to primers used for sequencing the fragments in conjunction with the PCR primers (DOC 60.5 KB)

Supplementary Fig. 1

Diagram of the constructs amplified by PCR for analysis of allelic variation in B-NK and B-lec between seven MHC haplotypes. The cartoon shows the B-NK and B-lec genes drawn to scale, with the exons shown as solid black boxes and untranslated regions as open boxes, with lines showing the various fragments amplified with the indicated primers and subsequently sequenced. The details of primers and PCR conditions are described in Supplementary Table 1, together with information on additional primers used for sequencing (PPT 212 KB)

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Rogers, S.L., Kaufman, J. High allelic polymorphism, moderate sequence diversity and diversifying selection for B-NK but not B-lec, the pair of lectin-like receptor genes in the chicken MHC. Immunogenetics 60, 461–475 (2008). https://doi.org/10.1007/s00251-008-0307-1

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