title: Selection and recombination drive the evolution of MHC class II DRB diversity in ungulates.
abstract: Major histocompatibility complex (MHC) antigen-presenting genes are the most variable loci in vertebrate genomes. Host-parasite co-evolution is assumed to maintain the excessive polymorphism in the MHC loci. However, the molecular mechanisms underlying the striking diversity in the MHC remain contentious. The extent to which recombination contributes to the diversity at MHC loci in natural populations is still controversial, and there have been only few comparative studies that make quantitative estimates of recombination rates. In this study, we performed a comparative analysis for 15 different ungulates species to estimate the population recombination rate, and to quantify levels of selection. As expected for all species, we observed signatures of strong positive selection, and identified individual residues experiencing selection that were congruent with those constituting the peptide-binding region of the human DRB gene. However, in addition for each species, we also observed recombination rates that were significantly different from zero on the basis of likelihood-permutation tests, and in other non-quantitative analyses. Patterns of synonymous and non-synonymous sequence diversity were consistent with differing demographic histories between species, but recent simulation studies by other authors suggest inference of selection and recombination is likely to be robust to such deviations from standard models. If high rates of recombination are common in MHC genes of other taxa, re-evaluation of many inference-based phylogenetic analyses of MHC loci, such as estimates of the divergence time of alleles and trans-specific polymorphism, may be required.
authors.affiliation: Konrad Lorenz Institute for Ethology, Vienna, Austria. H.Schaschl@gmx.net
authors.forename: H
authors.initials: H
authors.lastname: Schaschl
authors.forename: P
authors.initials: P
authors.lastname: Wandeler
authors.forename: F
authors.initials: F
authors.lastname: Suchentrunk
authors.forename: G
authors.initials: G
authors.lastname: Obexer-Ruff
authors.forename: S J
authors.initials: SJ
authors.lastname: Goodman
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D000835:Animals, Wild / Q000235:genetics*; D019143:Evolution, Molecular; D014644:Genetic Variation; D006041:Goats / Q000145:classification / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D008099:Liver / Q000378:metabolism; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011995:Recombination, Genetic; D012418:Ruminants / Q000235:genetics; D012641:Selection, Genetic; D017386:Sequence Homology, Amino Acid
chemical_list: D000949:Histocompatibility Antigens Class II