ORIGINAL PAPER Sequence analysis of the grey mouse lemur (Microcebus murinus) MHC class II DQ and DR region Anne Averdam & Christiane Kuschal & Nicole Otto & Nico Westphal & Christian Roos & Richard Reinhardt & Lutz Walter Received: 8 September 2010 / Accepted: 1 October 2010 / Published online: 12 October 2010 # Springer-Verlag 2010 Abstract We here report the genomic organisation of the grey mouse lemur (Microcebus murinus) MHC class II DQ and DR region based on BAC clone analysis. The sequenced Mimu-MHC haplotype spans 343 kb and encompasses the genes TAP2, DOB, DQB, DQA, DRB, DRA, BTNL2 and a further BTNL gene. The DQ and DR genes of this haplotype are not duplicated. Mimu-DOB is not transcribed and represents a pseudogene due to deletions and premature stop codons. Analysis of BAC clone DNA, a cDNA sample and eight genomic DNA samples suggests that Mimu-DRB, Mimu-DQA and Mimu-DQB are highly polymorphic with the majority of peptide-binding residues being affected by polymorphisms. In contrast, Mimu-DRA is moderately polymorphic, and the variable amino acid positions are not part of the peptide-binding region. Phylogenetic analysis of Mimu-DQA and Mimu-DQB and other primate DQA and DQB genes indicates that duplication of DQA and DQB loci occurred in Anthropoidea after the split from Strepsirrhini. Keywords MHC class II . Evolution . Polymorphism . Mouse lemur . BAC sequencing Introduction Classical major histocompatibility complex (MHC) class II molecules of the DR, DQ and DP type present peptides derived from exogenous antigens to CD4+ T lymphocytes (Swain 1983). The respective alpha and beta chain genes of these loci are expressed in professional antigen-presenting cells such as dendritic cells, macrophages, B cells and in thymus epithelia cells. Polymorphisms have been described for all loci, with species-specific differences. In humans, the beta chain-encoding genes are the most polymorphic ones, with 902 currently known DRB sequences, followed by 141 DPB1 and 112 DQB1 alleles. In contrast, the polymorphism of alpha chain-encoding genes in human is lower, with 35 DQA1, 28 DPA1 and only 3 DRA alleles (IMGT/HLA database, http://www.ebi.ac.uk/imgt/hla/). The vast major- ity of DRB polymorphism can be assigned to the HLA- DRB1 and HLA-DRB3 genes with currently 809 and 52 alleles, respectively. Additional functional (DRB4 and DRB5) and non-functional (DRB2, DRB6, DRB7, DRB8 and DRB9) genes are known, showing considerable copy number variations in human DR haplotypes (Beck and Trowsdale 1999). A. Averdam : C. Kuschal : N. Otto : N. Westphal : C. Roos : L. Walter Primate Genetics Laboratory, German Primate Center, Göttingen, Germany A. Averdam Department of Neurology, Klinikum Grosshadern, University of Munich, Munich, Germany C. Kuschal DNA Repair Section, DB, CCR, National Cancer Institute, NIH, Bethesda, MD, USA C. Roos : L. Walter Gene Bank of Primates, German Primate Center, Göttingen, Germany R. Reinhardt Genome Centre Cologne at Max Planck Institute for Plant Breeding Research, Köln, Germany L. Walter (*) Abteilung Primatengenetik, Deutsches Primatenzentrum, Kellnerweg 4, 37077 Göttingen, Germany e-mail: lwalter@gwdg.de Immunogenetics (2011) 63:85–93 DOI 10.1007/s00251-010-0487-3