title: No evidence of prenatal diversifying selection at locus or supertype levels in the dog MHC class II loci.
abstract: BACKGROUND
  Despite decades of studying, the mechanisms maintaining high diversity in the genes of the Major Histocompatibility Complex (MHC) are still puzzling scientists. In addition to pathogen recognition and other functions, MHC molecules may act prenatally in mate choice and in maternal-foetal interactions. These interactions are potential selective mechanisms that increase genetic diversity in the MHC. During pregnancy, immune response has a dual role: the foetus represents foreign tissue compared to mother, but histo-incompatibility is required for successful pregnancy. We have studied the prenatal selection in MHC class II loci (DLA-DQA1, DLA-DQB1 and DLA-DRB1) in domestic dogs by comparing the observed and expected offspring genotype proportions in 110 dog families. Several potential selection targets were addressed, including the peptide-binding site, the MHC locus, three-locus haplotype and supertype levels. For the supertype analysis, the first canine supertype classification was created based onin silicoanalysis of peptide-binding amino-acid polymorphism.
  
  
  RESULTS
  In most loci and levels, no deviation from the expected genotype frequencies was observed. However, one peptide-binding site in DLA-DRB1 had an excess of heterozygotes among the offspring. In addition, if the father shared a DLA-DRB1 allele with the mother, that allele was inherited by the offspring more frequently than expected, suggesting the selective advantage of a histo-compatible foetus, in contrast to our expectations.
  
  
  CONCLUSIONS
  We conclude that there is some evidence of post-copulatory selection at nucleotide site level in the MHC loci of pet dogs. But due to no indication of selection at locus, three-locus, or supertype levels, we estimated that the prenatal selection coefficient is less than 0.3 in domestic dogs and very likely other factors are more important in maintaining the genetic diversity in MHC loci.
authors.affiliation: Department of Genetics and Physiology, University of Oulu, PO Box 3000, Oulu, FIN-90014 Finland ; Present address: Centre for Biodiversity Dynamics, Department of Biology, Norwegian University of Science and Technology, NO -7491, Trondheim, Norway.
authors.forename: Alina K
authors.initials: AK
authors.lastname: Niskanen
authors.affiliation: Centre for Integrated Genomic Medical Research, University of Manchester, Stopford Building, Oxford Road, Manchester, M13 9PT UK.
authors.forename: Lorna J
authors.initials: LJ
authors.lastname: Kennedy
authors.affiliation: Department of Veterinary Biosciences, Research Programs Unit, Molecular Neurology, University of Helsinki and Folkhälsan Institute of Genetics, Biomedicum Helsinki, PO Box 63, FIN-00014 Helsinki, Finland.
authors.forename: Hannes
authors.initials: H
authors.lastname: Lohi
authors.affiliation: Department of Genetics and Physiology, University of Oulu, PO Box 3000, Oulu, FIN-90014 Finland.
authors.forename: Jouni
authors.initials: J
authors.lastname: Aspi
authors.affiliation: Department of Genetics and Physiology, University of Oulu, PO Box 3000, Oulu, FIN-90014 Finland.
authors.forename: Tanja
authors.initials: T
authors.lastname: Pyhäjärvi
keywords: Canis familiaris; MHC; Prenatal selection; Supertype classification