Department of Biodiversity Studies and Bioeducation, Faculty of Biology and Environmental Protection, University of Łódź, Banacha 1/3, 90-237, Łódź, Poland.
College of Animal Science and Technology, College of Veterinary Medicine, Zhejiang Agriculture and Forestry University, Hangzhou, China.
BMC Ecol Evol. 2021 May 8;21(1):80. doi: 10.1186/s12862-021-01812-x.
The Major Histocompatibility Complex (MHC) codes for the key vertebrate immune receptors responsible for pathogen recognition. Foreign antigens are recognized via their compatibility to hyper-variable region of the peptide-binding groove (PBR), which consists of two separate protein domains. Specifically, the PBR of the MHC class I receptors, which recognize intra-cellular pathogens, has two α domains encoded by exon 2 (α) and exon 3 (α) of the same gene. Most research on avian MHC class I polymorphism has traditionally focused exclusively on exon 3 and comparisons of selection between the two domains have been hampered by the scarcity of molecular data for exon 2. Thus, it is not clear whether the two domains vary in their specificity towards different antigens and whether they are subject to different selective pressure.
Here, we took advantage of rapidly accumulating genomic resources to test for the differences in selection patterns between both MHC class I domains of the peptide-binding groove in birds. For this purpose, we compiled a dataset of MHC class I exon 2 and 3 sequences for 120 avian species from 46 families. Our phylogenetically-robust approach provided strong evidence for highly consistent levels of selection on the α and α domains. There were strong correlations in all selection measures (number of positively/negatively selected residues and dN/dS ratios) between both PBR exons. Similar positive associations were found for the level of amino acid polymorphism across the two domains.
We conclude that the strength of selection and the level of polymorphism are highly consistent between both peptide-binding domains (α and α) of the avian MHC class I.
主要组织相容性复合体 (MHC) 编码脊椎动物负责识别病原体的关键免疫受体。通过其与肽结合槽 (PBR) 高变区的兼容性来识别外来抗原，该区域由两个独立的蛋白质结构域组成。具体而言，识别细胞内病原体的 MHC Ⅰ类受体的 PBR 由同一基因的外显子 2 (α) 和外显子 3 (α) 编码的两个α结构域组成。传统上，禽类 MHC Ⅰ类多态性的大多数研究都仅集中在外显子 3 上，由于缺乏外显子 2 的分子数据，因此比较两个结构域之间的选择受到阻碍。因此，尚不清楚这两个结构域在针对不同抗原的特异性方面是否存在差异，以及它们是否受到不同的选择压力。
在这里，我们利用快速积累的基因组资源，测试了禽类 PBR 两个 MHC Ⅰ类结构域之间选择模式的差异。为此，我们从 46 个科的 120 种鸟类中编译了 MHC Ⅰ类外显子 2 和 3 序列的数据集。我们的系统发育稳健方法为α和α结构域的选择高度一致提供了强有力的证据。所有选择指标（正/负选择残基数量和 dN/dS 比值）在两个 PBR 外显子之间都存在很强的相关性。两个结构域的氨基酸多态性水平也存在相似的正相关关系。
我们得出结论，禽类 MHC Ⅰ类的两个肽结合结构域（α和α）之间的选择强度和多态性水平高度一致。
