Mapping of positive selection sites in the HIV-1 genome in the context of RNA and protein structural constraints.
Mapping of positive selection sites in the HIV-1 genome in the context of RNA and protein structural constraints.
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DOI：
10.1186/1742-4690-8-87
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发表时间：
2011-11-01
期刊：
影响因子：
3.3
通讯作者：
Telenti A
中科院分区：
文献类型：
--
作者：
Snoeck J;Fellay J;Bartha I;Douek DC;Telenti A
HIV-1基因组受到针对病毒的压力，导致逃逸和适应。另一方面，由于功能和结构的限制，需要保持序列的保守性。绘制病毒基因组上的选择压力和保守位置图为理解病毒逃逸的限制提供了参考，并可以作为发现与已知或未知宿主蛋白的遗传冲突位置的模板。为了构建完整的HIV-1基因组进化、功能和结构图谱，从Los Alamos数据库获得了完整的B亚型序列。我们绘制了正选择压力、氨基酸保守性、蛋白质和RNA结构、重叠编码框架、CD8T细胞、CD4T细胞和抗体表位以及富含AG和AA二核苷酸动机的位点。在全球范围内，33%的氨基酸位置被发现是可变的，12%的基因组处于正向选择之下。由于相互关联的限制和多样化力量塑造了病毒基因组，我们将来自这两类压力的变量包括在一个多变量模型中，以预测保守或正选择：结构RNA域和α螺旋结构域独立预测保守，而CD4T细胞和抗体表位与正选择相关。病毒基因组的全球图谱包含不在规范的CD8T细胞、CD4T细胞或抗体表位中的阳性选择位点；因此，它识别了一类可能被其他宿主选择压力靶向的残基。总体而言，RNA结构代表了HIV-1保守的最强决定因素。这些数据可以为宿主和病毒遗传信息的联合分析提供信息。
The HIV-1 genome is subject to pressures that target the virus resulting in escape and adaptation. On the other hand, there is a requirement for sequence conservation because of functional and structural constraints. Mapping the sites of selective pressure and conservation on the viral genome generates a reference for understanding the limits to viral escape, and can serve as a template for the discovery of sites of genetic conflict with known or unknown host proteins. To build a thorough evolutionary, functional and structural map of the HIV-1 genome, complete subtype B sequences were obtained from the Los Alamos database. We mapped sites under positive selective pressure, amino acid conservation, protein and RNA structure, overlapping coding frames, CD8 T cell, CD4 T cell and antibody epitopes, and sites enriched in AG and AA dinucleotide motives. Globally, 33% of amino acid positions were found to be variable and 12% of the genome was under positive selection. Because interrelated constraining and diversifying forces shape the viral genome, we included the variables from both classes of pressure in a multivariate model to predict conservation or positive selection: structured RNA and α-helix domains independently predicted conservation while CD4 T cell and antibody epitopes were associated with positive selection. The global map of the viral genome contains positive selected sites that are not in canonical CD8 T cell, CD4 T cell or antibody epitopes; thus, it identifies a class of residues that may be targeted by other host selective pressures. Overall, RNA structure represents the strongest determinant of HIV-1 conservation. These data can inform the combined analysis of host and viral genetic information.
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