Niskanen Alina K, Kennedy Lorna J, Lohi Hannes, Aspi Jouni, Pyhäjärvi Tanja
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.
Centre for Integrated Genomic Medical Research, University of Manchester, Stopford Building, Oxford Road, Manchester, M13 9PT UK.
Canine Genet Epidemiol. 2016 Nov 18;3:9. doi: 10.1186/s40575-016-0038-9. eCollection 2016.
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 on analysis of peptide-binding amino-acid polymorphism.
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.
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.
尽管经过数十年的研究，但主要组织相容性复合体（MHC）基因中维持高度多样性的机制仍令科学家们困惑不解。除了病原体识别和其他功能外，MHC分子可能在产前的配偶选择和母婴相互作用中发挥作用。这些相互作用是增加MHC基因多样性的潜在选择机制。在怀孕期间，免疫反应具有双重作用：与母亲相比，胎儿代表外来组织，但成功怀孕需要组织不相容性。我们通过比较110个犬科家庭中观察到的和预期的后代基因型比例，研究了家犬MHC II类基因座（DLA - DQA1、DLA - DQB1和DLA - DRB1）的产前选择。研究了几个潜在的选择靶点，包括肽结合位点、MHC基因座、三位点单倍型和超型水平。对于超型分析，基于肽结合氨基酸多态性分析创建了首个犬类超型分类。
在大多数基因座和水平上，未观察到与预期基因型频率的偏差。然而，DLA - DRB1中的一个肽结合位点在后代中杂合子过多。此外，如果父亲与母亲共享一个DLA - DRB1等位基因，该等位基因被后代遗传的频率高于预期，这表明与我们的预期相反，组织相容性胎儿具有选择优势。
我们得出结论，宠物狗的MHC基因座在核苷酸位点水平上有一些交配后选择的证据。但由于在基因座、三位点或超型水平上没有选择的迹象，我们估计家犬的产前选择系数小于0.3，而且很可能其他因素在维持MHC基因座的遗传多样性方面更重要。
