title: Evolution of major histocompatibility complex class I and class II genes in the brown bear.
abstract: BACKGROUND
  Major histocompatibility complex (MHC) proteins constitute an essential component of the vertebrate immune response, and are coded by the most polymorphic of the vertebrate genes. Here, we investigated sequence variation and evolution of MHC class I and class II DRB, DQA and DQB genes in the brown bear Ursus arctos to characterise the level of polymorphism, estimate the strength of positive selection acting on them, and assess the extent of gene orthology and trans-species polymorphism in Ursidae.
  
  
  RESULTS
  We found 37 MHC class I, 16 MHC class II DRB, four DQB and two DQA alleles. We confirmed the expression of several loci: three MHC class I, two DRB, two DQB and one DQA. MHC class I also contained two clusters of non-expressed sequences. MHC class I and DRB allele frequencies differed between northern and southern populations of the Scandinavian brown bear. The rate of nonsynonymous substitutions (dN) exceeded the rate of synonymous substitutions (dS) at putative antigen binding sites of DRB and DQB loci and, marginally significantly, at MHC class I loci. Models of codon evolution supported positive selection at DRB and MHC class I loci. Both MHC class I and MHC class II sequences showed orthology to gene clusters found in the giant panda Ailuropoda melanoleuca.
  
  
  CONCLUSIONS
  Historical positive selection has acted on MHC class I, class II DRB and DQB, but not on the DQA locus. The signal of historical positive selection on the DRB locus was particularly strong, which may be a general feature of caniforms. The presence of MHC class I pseudogenes may indicate faster gene turnover in this class through the birth-and-death process. South-north population structure at MHC loci probably reflects origin of the populations from separate glacial refugia.
authors.affiliation: Institute of Environmental Sciences, Jagiellonian University, Kraków, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kuduk
authors.forename: Wiesław
authors.initials: W
authors.lastname: Babik
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Bojarska
authors.forename: Ewa B
authors.initials: EB
authors.lastname: Sliwińska
authors.forename: Jonas
authors.initials: J
authors.lastname: Kindberg
authors.forename: Pierre
authors.initials: P
authors.lastname: Taberlet
authors.forename: Jon E
authors.initials: JE
authors.lastname: Swenson
authors.forename: Jacek
authors.initials: J
authors.lastname: Radwan
mesh_terms: D000818:Animals; D019143:Evolution, Molecular; D005091:Exons; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D010802:Phylogeny; D011544:Pseudogenes; D012537:Scandinavian and Nordic Countries; D001503:Ursidae / Q000235:genetics* / Q000276:immunology
chemical_list: D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II