Contrasted evolutionary histories of two Toll-like receptors (Tlr4 and Tlr7) in wild rodents (MURINAE).
Contrasted evolutionary histories of two Toll-like receptors (Tlr4 and Tlr7) in wild rodents (MURINAE).
复制标题
DOI：
10.1186/1471-2148-13-194
复制
发表时间：
2013-09-12
影响因子：
3.4
通讯作者：
Cosson JF
中科院分区：
文献类型：
--
作者：
Fornůsková A;Vinkler M;Pagès M;Galan M;Jousselin E;Cerqueira F;Morand S;Charbonnel N;Bryja J;Cosson JF
在脊椎动物中，已经反复证明，编码通过适应性免疫参与病原体识别的蛋白质（例如MHC）的基因受到密集的多样化选择。另一方面，塑造先天免疫基因进化的选择过程的作用和类型目前还不太清楚。在这项研究中，我们分析了自然变异和进化过程中的两个基因参与的先天免疫识别的微生物相关的分子模式（MAMPs）。我们对编码Toll样受体4（Tlr4）和7（Tlr7）的基因进行了测序，Toll样受体4和7是先天免疫的两种关键细菌和病毒感应受体，分布在鼠科亚科的23个物种中。虽然我们已经表明，两个TLR基因的同源性在很大程度上是一致的啮齿动物的同源性的基础上一个大规模的非免疫序列数据集，我们还确定了几个潜在的重要差异。序列分析显示，两个Tlr的主要部分在强烈的纯化选择下进化，可能是由于功能限制。然而，在这两个基因中也发现了几个正选择的特征，其中细菌感测Tlr4中的信号比病毒感测Tlr7中的信号更强。在Tlr4和Tlr7中，分别有92%和100%的在正选择下进化的位点位于细胞外结构域中。直接在TLR4的配体结合区（LBR）中，我们确定了两个快速进化的氨基酸残基和一个正选择位点，所有这三个可能涉及革兰氏阴性菌的脂多糖的种特异性识别。与此相反，所有推定的位点LBRTLR7参与检测病毒核酸是高度保守的啮齿动物。种间差异的预测的三维结构的LBR的两个Tlrs不相关的系统发育史，而蛋白质电荷的分析清楚地区分Rattini和Murini分支。由于受体蛋白功能的限制，纯化选择已经成为Tlr进化的主导力量。然而，我们的研究结果表明，情节多样化的寄生虫介导的选择塑造了目前的物种特异性变异啮齿动物类Tlrs。多样化选择的强度在Tlr4中比在Tlr7中更高，这可能是由于它们的配体的结构特性。
In vertebrates, it has been repeatedly demonstrated that genes encoding proteins involved in pathogen-recognition by adaptive immunity (e.g. MHC) are subject to intensive diversifying selection. On the other hand, the role and the type of selection processes shaping the evolution of innate-immunity genes are currently far less clear. In this study we analysed the natural variation and the evolutionary processes acting on two genes involved in the innate-immunity recognition of Microbe-Associated Molecular Patterns (MAMPs). We sequenced genes encoding Toll-like receptor 4 (Tlr4) and 7 (Tlr7), two of the key bacterial- and viral-sensing receptors of innate immunity, across 23 species within the subfamily Murinae. Although we have shown that the phylogeny of both Tlr genes is largely congruent with the phylogeny of rodents based on a comparably sized non-immune sequence dataset, we also identified several potentially important discrepancies. The sequence analyses revealed that major parts of both Tlrs are evolving under strong purifying selection, likely due to functional constraints. Yet, also several signatures of positive selection have been found in both genes, with more intense signal in the bacterial-sensing Tlr4 than in the viral-sensing Tlr7. 92% and 100% of sites evolving under positive selection in Tlr4 and Tlr7, respectively, were located in the extracellular domain. Directly in the Ligand-Binding Region (LBR) of TLR4 we identified two rapidly evolving amino acid residues and one site under positive selection, all three likely involved in species-specific recognition of lipopolysaccharide of gram-negative bacteria. In contrast, all putative sites of LBRTLR7 involved in the detection of viral nucleic acids were highly conserved across rodents. Interspecific differences in the predicted 3D-structure of the LBR of both Tlrs were not related to phylogenetic history, while analyses of protein charges clearly discriminated Rattini and Murini clades. In consequence of the constraints given by the receptor protein function purifying selection has been a dominant force in evolution of Tlrs. Nevertheless, our results show that episodic diversifying parasite-mediated selection has shaped the present species-specific variability in rodent Tlrs. The intensity of diversifying selection was higher in Tlr4 than in Tlr7, presumably due to structural properties of their ligands.
登录
查看更多内容
影响因子：
4.4
作者：
Downing, Tim;Lloyd, Andrew T.;Bradley, Daniel G.
通讯作者：
Bradley, Daniel G.
影响因子：
3.2
作者：
Bryja, J;Galan, M;Cosson, JF
通讯作者：
Cosson, JF
影响因子：
3.7
作者：
Aplin KP;Suzuki H;Chinen AA;Chesser RT;Ten Have J;Donnellan SC;Austin J;Frost A;Gonzalez JP;Herbreteau V;Catzeflis F;Soubrier J;Fang YP;Robins J;Matisoo-Smith E;Bastos AD;Maryanto I;Sinaga MH;Denys C;Van Den Bussche RA;Conroy C;Rowe K;Cooper A
通讯作者：
Cooper A
DOI：
10.1073/pnas.0502040102
发表时间：
2005-06-28
影响因子：
11.1
作者：
Andersen-Nissen, E;Smith, KD;Aderem, A
通讯作者：
Aderem, A
影响因子：
10.7
作者：
Alcaide, Miguel;Edwards, Scott V.
通讯作者：
Edwards, Scott V.