Diversifying and purifying selection in the peptide binding region of DRB in mammals
Diversifying and purifying selection in the peptide binding region of DRB in mammals
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DOI：
10.1007/s00239-008-9092-6
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发表时间：
2008-04-01
影响因子：
3.9
通讯作者：
Yang, Ziheng
中科院分区：
文献类型：
--
作者：
Furlong, Rebecca F.;Yang, Ziheng
主要组织相容性复合体的II类基因编码在抗原提呈中起关键作用的蛋白质。它们是已知的最多态的蛋白质之一，这种多态被认为是自然选择的结果。为了了解作用在蛋白质上的选择压力，并检验物种之间可能存在的进化动力学差异，我们应用密码子替换的最大似然模型分析了六个哺乳动物物种的DRB基因：人、黑猩猩、猕猴、塔玛兰、狗和牛。这些模型考虑了基因中不同密码子的不同选择压力，并有能力在正选择或负选择下检测氨基酸残基。我们的分析发现，在所研究的六种哺乳动物中，每一种都存在DRB基因的阳性选择。与结构数据的比较表明，几乎所有在人类中被推测为正向选择的氨基酸残基都在多肽结合区(PBR)上，并与抗原侧链接触，尽管也检测到PBR之外但接近PBR的残基。在PBR中，在与抗原接触的部位以及可能参与二聚化或T细胞结合的部位也检测到强烈的纯化选择。分析表明，即使在结构信息可用的情况下，随机场地分析也是有用的。不同的哺乳动物物种被发现共享许多正或负选择的位点，这表明尽管不同物种的栖息地和病原体不同，但它们的功能角色在不同物种中仍然非常相似。
The class II genes of the major histocompatibility complex encode proteins which play a crucial role in antigen presentation. They are among the most polymorphic proteins known, and this polymorphism is thought to be the result of natural selection. To understand the selective pressure acting on the protein and to examine possible differences in the evolutionary dynamics among species, we apply maximum likelihood models of codon substitution to analyze the DRB genes of six mammalian species: human, chimpanzee, macaque, tamarin, dog, and cow. The models account for variable selective pressures across codons in the gene and have the power to detect amino acid residues under either positive or negative selection. Our analysis detected positive selection in the DRB genes in each of the six mammals examined. Comparison with structural data reveals that almost all amino acid residues inferred to be under positive selection in humans are in the peptide binding region (PBR) and are in contact with the antigen side chains, although residues outside of but close to the PBR are also detected. Strong purifying selection is also detected in the PBR, at sites which contact the antigen and at sites which may be involved in dimerization or T cell binding. The analysis demonstrates the utility of the random-sites analysis even when structural information is available. The different mammalian species are found to share many positively or negatively selected sites, suggesting that their functional roles have remained very similar in the different species, despite the different habitats and pathogens of the species.