Lukacs et al. BMC Genomics 2010, 11:154 http://www.biomedcentral.com/1471-2164/11/154 R E S E A R C H A R T I C L E Open Access Comprehensive analysis of MHC class I genes from the U-, S-, and Z-lineages in Atlantic salmon Morten F Lukacs1†, Håvard Harstad1†, Hege G Bakke2, Marianne Beetz-Sargent3, Linda McKinnel3, Krzysztof P Lubieniecki4, Ben F Koop3, Unni Grimholt2* Abstract Background: We have previously sequenced more than 500 kb of the duplicated MHC class I regions in Atlantic salmon. In the IA region we identified the loci for the MHC class I gene Sasa-UBA in addition to a soluble MHC class I molecule, Sasa-ULA. A pseudolocus for Sasa-UCA was identified in the nonclassical IB region. Both regions contained genes for antigen presentation, as wells as orthologues to other genes residing in the human MHC region. Results: The genomic localisation of two MHC class I lineages (Z and S) has been resolved. 7 BACs were sequenced using a combination of standard Sanger and 454 sequencing. The new sequence data extended the IA region with 150 kb identifying the location of one Z-lineage locus, ZAA. The IB region was extended with 350 kb including three new Z-lineage loci, ZBA, ZCA and ZDA in addition to a UGA locus. An allelic version of the IB region contained a functional UDA locus in addition to the UCA pseudolocus. Additionally a BAC harbouring two MHC class I genes (UHA) was placed on linkage group 14, while a BAC containing the S-lineage locus SAA (previously known as UAA) was placed on LG10. Gene expression studies showed limited expression range for all class I genes with exception of UBA being dominantly expressed in gut, spleen and gills, and ZAA with high expression in blood. Conclusion: Here we describe the genomic organization of MHC class I loci from the U-, Z-, and S-lineages in Atlantic salmon. Nine of the described class I genes are located in the extension of the duplicated IA and IB regions, while three class I genes are found on two separate linkage groups. The gene organization of the two regions indicates that the IB region is evolving at a different pace than the IA region. Expression profiling, polymorphic content, peptide binding properties and phylogenetic relationship show that Atlantic salmon has only one MHC class Ia gene (UBA), in addition to a multitude of nonclassical MHC class I genes from the U-, S- and Z-lineages. Background Major histocompatibility complex (MHC) class I mole- cules have important roles in presenting antigens to immune cells thereby enabling the organism to discrimi- nate between self and non-self. In humans, the MHC genomic region is a gene dense region covering more than 4 Mb and encodes MHC class I and II molecules in addition to numerous other immune related mole- cules. The classical MHC region is located on chromo- some 6, while duplicated regions are found on chromosomes 1, 9 and 19, resulting from two whole- * Correspondence: unni.grimholt@bio.uio.no † Contributed equally 2Centre for Ecology and Evolutionary Synthesis, Dept of Biology, University of Oslo, Norway genome duplications [1]. The primary form of the MHC class I molecule consists of an alpha chain, stabilized by a b2-microglobulin (b2 m) molecule. MHC class I molecules are at present divided into two main categories; classical MHC class I (or Ia) and non- classical MHC class I (or Ib) where the latter category contains a multitude of molecules with various ligand binding abilities. MHC class Ia molecules are extremely polymorphic and expressed in most cells where they present self and nonself peptides primarily to CD8+ T-cells. In humans the MHC class Ia molecules are encoded by the HLA-A, HLA-B and HLA-C loci. The MHC class Ib molecules are less polymorphic and have a more restricted tissue distribution. The MHC class Ib family include the peptide binders like HLA-E, HLA-F, © 2010 Lukacs et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.