Phylogenetic Relationships and Molecular Adaptation Dynamics of Human Rhinoviruses
Phylogenetic Relationships and Molecular Adaptation Dynamics of Human Rhinoviruses
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DOI：
10.1093/molbev/msp009
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发表时间：
2009-05-01
影响因子：
10.7
通讯作者：
Crandall, Keith A.
中科院分区：
文献类型：
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作者：
Lewis-Rogers, Nicole;Bendall, Matthew L.;Crandall, Keith A.
人类鼻病毒（HRV）是近50%的普通感冒感染的原因。通常，HRV感染是温和的和自限性的;然而，每年它们都会导致经济生产力的重大损失和大量不适当的抗生素使用。针对HRV的有效疫苗和抗病毒预防的开发受到近100种血清型中存在的广泛抗原多样性的阻碍。为了获得新的见解的进化过程中，创造的遗传多样性之间存在的HRV，我们测试了重组和选择的个别基因和编码基因组的45 HRV血清型使用估计的系统发育关系。虽然结构衣壳基因和非结构基因恢复不一致的树拓扑结构，没有重组检测到使用替代方法。因此，确定编码基因组适合用于系统发育测试。SHIMODAIRA-HASEGAWA（SH）检验的结果支持衣壳基因恢复了与非结构基因不同的进化历史的假设。我们最好的系统发育估计的基础上的编码基因组表明，HRV-B是更密切相关的肠道病毒比HRV-A，然而，几个替代的系统发育假说没有被拒绝的SH测试。通过使用两种不同的方法检查正选择; d（N）/d（S）比率和31个氨基酸特性的理化表型。使用d（N）/d（S）的分析未能检测到阳性选择。然而，蛋白质表型表达似乎是更敏感的方法。在HRV-A主要血清型和HRV-B血清型中，除了HRV-B中的3A外，所有蛋白质都存在广泛的稳定和不稳定的正选择，3A与功能，结构重叠，并且在更大程度上在未表征的基因组区域中。相反，HRV-A次要血清型的进化似乎主要由不稳定选择驱动。我们的研究结果表明，HRV-A主要，HRV-A次要，和HRV-B血清型没有类似的影响，纯化选择。
Human rhinoviruses (HRVs) are responsible for nearly 50% of all common cold infections. Ordinarily, HRV infections are mild and self-limiting; nonetheless, every year they result in significant loss of economic productivity and substantial inappropriate antibiotic use. Development of effective vaccine and antiviral prophylaxis against HRV has been hampered by the extensive antigenic diversity present among the nearly 100 serotypes. To gain new insights into the evolutionary processes that create the genetic diversity present among HRVs, we tested for recombination and selection for individual genes and the coding genome for 45 HRV serotypes using estimated phylogenetic relationships. Although the structural capsid genes and nonstructural genes recovered incongruent tree topologies, no recombination was detected using substitution methods. Therefore, the coding genome was determined to be appropriate for phylogenetic tests. Results of the Shimodaira-Hasegawa (SH) test support the hypothesis that the capsid genes recover a different evolutionary history than the nonstructural genes. Our best phylogenetic estimate based on the coding genome suggests that HRV-B is more closely related to enterovirus than to HRV-A; however, several alternative phylogenetic hypotheses were not rejected by the SH test. Positive selection was examined by using two different approaches; d(N)/d(S) rate ratio and the physicochemical phenotypes for 31 amino acid properties. Analyses using d(N)/d(S) failed to detect positive selection. However, protein phenotypic expression appears to be a more sensitive approach. There was extensive stabilizing and destabilizing positive selection in HRV-A major and HRV-B serotypes for all proteins, except in 3A in HRV-B, which overlapped with functional, structural, and to a greater extent in uncharacterized genomic regions. In contrast, the evolution of HRV-A minor serotypes appears to be driven primarily by destabilizing selection. Our results demonstrate that HRV-A major, HRV-A minor, and HRV-B serotypes have not been similarly influenced by purifying selection.