The orthology of HLA-E and H2-Qa1 is hidden by their concerted evolution with other MHC class I molecules
The orthology of HLA-E and H2-Qa1 is hidden by their concerted evolution with other MHC class I molecules
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DOI：
10.1186/1745-6150-1-2
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发表时间：
2006-01-31
期刊：
影响因子：
5.5
通讯作者：
Rouillon, Virginie
中科院分区：
文献类型：
--
作者：
Joly, Etienne;Rouillon, Virginie
背景资料：是否MHC分子进行协调进化或不一直是一个长期的debate.Results的主题：通过比较从灵长类动物和啮齿类动物的HLA-E的8个功能同源物与相同的8个物种的MHC Ia类分子的序列，我们发现，MHC I类分子的不同部分进行不同的进化模式。通过集中我们的分析顺序对这些不同的部分，我们已经获得了明确的证据，协调进化的MHC I类分子，这表明发生了广泛的等位基因间和基因间的交流。在编码α 3结构域的外显子4的水平上，序列的种内均质化特别明显，但我们的结果表明，均质化还涉及α 1-α 2共结构域的某些残基，这些残基位于抗原识别位点之外。提出了一个模型，在该模型中，由于病原体的达尔文选择压力可以，在同一时间，有利于MHC Ia类分子的多样化，并通过将由单个MHC分子中的突变产生的有利基序传播到其它等位基因和MHC区域的其它基因座来促进单独基因座的协同进化。这也将允许MHC分子与它们相互作用的蛋白质共同进化，以实现其抗原呈递和NK细胞活性调节的功能。因此，MHC存在的理由之一可能是同时有利于MHC Ia类分子的多样化和参与抗原呈递的MHC I类分子（Ia和Ib）的整个库的均质化。
Background: Whether MHC molecules undergo concerted evolution or not has been the subject of a long-standing debate.Results: By comparing sequences of eight functional homologues of HLA-E from primates and rodents with those of MHC class Ia molecules from the same eight species, we find that different portions of MHC class I molecules undergo different patterns of evolution. By focusing our analyses sequentially on these various portions, we have obtained clear evidence for concerted evolution of MHC class I molecules, suggesting the occurrence of extensive interallelic and intergenic exchanges. Intra-species homogenisation of sequences is particularly noticeable at the level of exon 4, which codes for the alpha 3 domain, but our results suggest that homogenisation also concerns certain residues of the alpha 1-alpha 2 codomain that lie outside the antigen recognition site.Conclusion: A model is presented in which Darwinian selective pressures due to pathogens could, at the same time, favour diversification of MHC class Ia molecules and promote concerted evolution of separate loci by spreading advantageous motifs arising by mutations in individual MHC molecules to other alleles and to other loci of the MHC region. This would also allow MHC molecules to co-evolve with the proteins with which they interact to fulfil their functions of antigen presentation and regulation of NK cell activity. One of the raisons d'etre of the MHC may therefore be to favour at the same time both diversification of MHC class Ia molecules and homogenisation of the whole pool of MHC class I molecules (Ia and Ib) involved in antigen presentation.