Evolution of the porcine (Sus scrofa domestica) immunoglobulin kappa locus through germline gene conversion
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Immunoglobulin (IG) gene rearrangement and expression are central to disease resistance and health maintenance in animals. The IG kappa (IGK) locus in swine (Sus scrofa domestica) contributes to approximately half of all antibody molecules, in contrast to many other Cetartiodactyla, whose members provide the majority of human dietary protein and in which kappa locus utilization is limited. The porcine IGK variable locus is 27.9 kb upstream of five IG kappa J genes (IGKJ) which are separated from a single constant gene (IGKC) by 2.8 kb. Fourteen variable genes (IGKV) were identified, of which nine are functional and two are open reading frame (ORF). Of the three pseudogenes, IGKV3-1 contains a frameshift and multiple stop codons, IGKV7-2 contains multiple stop codons, and IGKV2-5 is missing exon 2. The nine functional IGKV genes are phylogenetically related to either the human IGKV1 or IGKV2 subgroups. IGKV2 subgroup genes were found to be dominantly expressed. Polymorphisms were identified on overlapping BACs derived from the same individual such that 11 genes contain amino acid differences. The most striking allelic differences are present in IGKV2 genes, which contain as many as 16 amino acid changes between alleles, the majority of which are in complementarity determining region (CDR) 1. In addition, many IGKV2 CDR1 are shared between genes but not between alleles, suggesting extensive diversification of this locus through gene conversion.
KeywordsSus scrofa Porcine Light chain kappa Polymorphism Gene conversion
We thank Erin Babineau for excellent technical assistance, and Dr. Jane Loveland for her generous review of the manuscript. This work was supported by a grant from the National Pork Board (10–139).
- Eguchi-Ogawa T, Wertz N, Sun XZ, Puimi F, Uenishi H, Wells K, Chardon P, Tobin GJ, Butler JE (2010) Antibody repertoire development in fetal and neonatal piglets. XI. The relationship of variable heavy chain gene usage and the genomic organization of the variable heavy chain locus. J Immunol 184:3734–3742PubMedCrossRefGoogle Scholar
- Gorodkin J, Cirera S, Hedegaard J, Gilchrist MJ, Panitz F, Jørgensen C, Scheibye-Knudsen K, Arvin T, Lumholdt S, Sawera M, Green T, Nielsen BJ, Havgaard JH, Rosenkilde C, Wang J, Li H, Li R, Liu B, Hu S, Dong W, Li W, Yu J, Wang J, Stærfeldt H, Wernersson R, Madsen LB, Thomsen B, Hornshøj H, Bujie Z, Wang X, Wang X, Bolund L, Brunak S, Yang H, Bendixen C, Fredholm M (2007) Porcine transcriptome analysis based on 97 non-normalized cDNA libraries and assembly of 1,021,891 expressed sequence tags. Genome Biol 8:R45PubMedCrossRefGoogle Scholar
- Hubbard T, Barker D, Birney E, Cameron G, Chen Y, Clark L, Cox T, Cuff J, Curwen V, Down T, Durbin R, Eyras E, Gilbert J, Hammond M, Huminiecki L, Kasprzyk A, Lehvaslaiho H, Lijnzaad P, Melsopp C, Mongin E, Pettett R, Pocock M, Potter S, Rust A, Schmidt E, Searle S, Slater G, Smith J, Spooner W, Stabenau A, Stalker J, Stupka E, Ureta-Vidal A, Vastrik I, Clamp M (2002) The Ensembl genome database project. Nucleic Acids Res 30:38–41Google Scholar
- Humphray SJ, Scott CE, Clark R, Marron B, Bender C, Camm N, Davis J, Jenks A, Noon A, Patel M, Sehra H, Yang F, Rogatcheva MB, Milan D, Chardon P, Rohrer G, Nonneman D, de Jong P, Meyers SN, Archibald A, Beever JE, Schook LB, Rogers J (2007) A high utility map of the pig genome. Genome Biol 8:R139PubMedCrossRefGoogle Scholar
- Lefranc M-P, Lefranc G (2001) The immunoglobulin FactsBook. Academic, London, pp 1–458Google Scholar
- Lefranc M-P, Pommié C, Kaas Q, Duprat E, Bosc N, Guiraudou D, Jean C, Ruiz M, Da Piédade I, Rouard M, Foulquier E, Thouvenin V, Lefranc G (2005) IMGT unique numbering for immunoglobulin and T cell receptor constant domains and Ig superfamily C-like domains. Dev Comp Immunol 29:185–203PubMedCrossRefGoogle Scholar