Patterns of evolution and host gene mimicry in influenza and other RNA viruses.
Patterns of evolution and host gene mimicry in influenza and other RNA viruses.
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DOI：
10.1371/journal.ppat.1000079
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发表时间：
2008-06-06
期刊：
影响因子：
6.7
通讯作者：
Rabadan R
中科院分区：
文献类型：
--
作者：
Greenbaum BD;Levine AJ;Bhanot G;Rabadan R
众所周知，二核苷酸 CpG 在许多脊椎动物的基因组 DNA 中代表性不足。这通常被认为是由于该二核苷酸中胞嘧啶残基的甲基化以及相应的 5-甲基胞嘧啶的高脱氨率，从而降低了该二核苷酸在 DNA 中的频率。令人惊讶的是，许多在这些脊椎动物宿主中复制的单链 RNA 病毒的基因组中 CpG 二核苷酸的含量也非常低。病毒是专性细胞内寄生虫，病毒的进化与其宿主的性质和命运密切相关。因此，人们期望病毒和宿主基因组应该具有共同的特征。在这项工作中，我们比较了 ssRNA 病毒及其宿主基因组的进化模式。特别是，我们分析了二核苷酸模式，发现相同的模式在许多 RNA 病毒及其宿主中普遍过度或不足，这表明许多 RNA 病毒通过模仿宿主基因 (DNA) 的一些特征而进化，也可能模仿其相应的 mRNA。当病毒跨越物种屏障进入不同的宿主时，复制、生存和适应的压力会在二核苷酸频率中留下足迹。例如，由于人类基因似乎比鸟类基因面临更高的消除 CpG 二核苷酸基序的压力，因此与在鸟类宿主中复制的相同病毒相比，这种压力可能反映在人类病毒（DNA 和 RNA 病毒）的基因组中。为了检验这个想法，我们分析了自 1918 年以来流感病毒的进化。我们发现甲型流感病毒起源于禽类宿主，并在人类中复制了许多代，其进化方向经过严格选择，以降低其基因组中 CpG 二核苷酸的频率。与这一观察结果一致，我们发现乙型流感病毒在人群中度过了更长的时间，已经适应了人类宿主，并且表现出极低的 CpG 二核苷酸含量。我们相信这些观察结果直接表明RNA病毒基因组的进化可以通过在宿主基因组中观察到的压力来塑造。作为一种可能的解释，我们认为作用于这些 RNA 病毒的强大选择压力很可能与先天免疫反应以及宿主 DNA 和 RNA 中的核苷酸基序有关。病毒是专性细胞内寄生虫，它们使用不同的策略来隔离宿主细胞机器并避开宿主免疫系统。在本文中，我们探索了以单链 RNA 编码其遗传信息的病毒基因组，单链 RNA 是一种与其宿主使用的材料（双链 DNA）不同的材料。有趣的是，这些病毒具有一些宿主的共同特征。例如，脊椎动物 DNA 中最不常见的基序之一是二核苷酸 CpG。这通常被认为是由于该二核苷酸中胞嘧啶残基的甲基化和脱氨基作用所致。令人惊讶的是，在脊椎动物 RNA 病毒中观察到相同的 CpG 抑制，但在 RNA 噬菌体中却没有。我们发现 RNA 病毒呈现出与其宿主基因相似的二核苷酸压力。我们发现甲型流感病毒起源于禽类宿主，并在人类体内复制了许多代，其进化过程降低了模仿人类基因的 CpG 二核苷酸的频率。乙型流感在人类中存在时间较长，其 CpG 二核苷酸含量极低。这些观察结果表明，RNA 病毒的进化是由宿主基因组中观察到的压力决定的。
It is well known that the dinucleotide CpG is under-represented in the genomic DNA of many vertebrates. This is commonly thought to be due to the methylation of cytosine residues in this dinucleotide and the corresponding high rate of deamination of 5-methycytosine, which lowers the frequency of this dinucleotide in DNA. Surprisingly, many single-stranded RNA viruses that replicate in these vertebrate hosts also have a very low presence of CpG dinucleotides in their genomes. Viruses are obligate intracellular parasites and the evolution of a virus is inexorably linked to the nature and fate of its host. One therefore expects that virus and host genomes should have common features. In this work, we compare evolutionary patterns in the genomes of ssRNA viruses and their hosts. In particular, we have analyzed dinucleotide patterns and found that the same patterns are pervasively over- or under-represented in many RNA viruses and their hosts suggesting that many RNA viruses evolve by mimicking some of the features of their host's genes (DNA) and likely also their corresponding mRNAs. When a virus crosses a species barrier into a different host, the pressure to replicate, survive and adapt, leaves a footprint in dinucleotide frequencies. For instance, since human genes seem to be under higher pressure to eliminate CpG dinucleotide motifs than avian genes, this pressure might be reflected in the genomes of human viruses (DNA and RNA viruses) when compared to those of the same viruses replicating in avian hosts. To test this idea we have analyzed the evolution of the influenza virus since 1918. We find that the influenza A virus, which originated from an avian reservoir and has been replicating in humans over many generations, evolves in a direction strongly selected to reduce the frequency of CpG dinucleotides in its genome. Consistent with this observation, we find that the influenza B virus, which has spent much more time in the human population, has adapted to its human host and exhibits an extremely low CpG dinucleotide content. We believe that these observations directly show that the evolution of RNA viral genomes can be shaped by pressures observed in the host genome. As a possible explanation, we suggest that the strong selection pressures acting on these RNA viruses are most likely related to the innate immune response and to nucleotide motifs in the host DNA and RNAs. Viruses are obligate intracellular parasites that use different strategies to sequester host cell machinery and avoid the host immune system. In this paper we explore the genomes of viruses that encode their genetic information in single-stranded RNA, a different material than the one used by their hosts (double-stranded DNA). It is interesting to observe that these viruses share some of the host's characteristics. For instance, one of the most underrepresented motifs in the DNA of vertebrates is the dinucleotide CpG. This is commonly thought to be due to methylation and deamination of cytosine residues in this dinucleotide. Surprisingly, the same CpG suppression is observed in vertebrate RNA viruses but not in RNA phages. We show that RNA viruses present similar dinucleotide pressures as their host genes. We find that the influenza A virus, which originated from an avian reservoir and replicated in humans over many generations, evolves to reduce the frequency of CpG dinucleotides mimicking the human genes. Influenza B, which has been in humans longer, exhibits an extremely low CpG dinucleotide content. These observations suggest that the evolution of RNA viruses is shaped by pressures observed in the host genome.
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