Molecular Developmental Physiology and Signal Transduction, KU Leuven, Naamsestraat 59, P.O. Box 02465, B-3000, Leuven, Belgium.
Sci Rep. 2017 Aug 23;7(1):9230. doi: 10.1038/s41598-017-08043-5.
In addition to mediating regulation of endogenous gene expression, RNA interference (RNAi) in plants and invertebrates plays a crucial role in defense against viruses via virus-specific siRNAs. Different studies have demonstrated that the functional diversity of RNAi in animals is linked to the diversification of the Argonaute superfamily, central components of RISCs (RNA induced silencing complexes). The animal Argonaute superfamily is traditionally grouped into AGO and PIWI Argonautes. Yet, by performing phylogenetic analyses and determining the selective evolutionary pressure in the metazoan Argonaute superfamily, we provide evidence for the existence of three conserved Argonaute lineages between basal metazoans and protostomes, namely siRNA-class AGO, miRNA-class AGO and PIWI Argonautes. In addition, it shown that the siRNA-class AGO lineage is characterized by high rates of molecular evolution, suggesting a role in the arms race with viruses, while the miRNA-class AGOs display strong sequence conservation. Interestingly, we also demonstrate that vertebrates lack siRNA-class AGO proteins and that vertebrate AGOs display low rates of molecular evolution. In this way, we provide supportive evidence for the loss of the antiviral siRNA-class AGO group in vertebrates and discuss the consequence hereof on antiviral immunity and the use of RNAi as a loss of function tool in these animals.
除了介导内源性基因表达的调控外，植物和无脊椎动物中的 RNA 干扰 (RNAi) 通过病毒特异性 siRNAs 在抗病毒防御中也起着至关重要的作用。不同的研究表明，动物中 RNAi 的功能多样性与 Argonaute 超家族的多样化有关，Argonaute 超家族是 RISCs（RNA 诱导沉默复合物）的核心组成部分。动物 Argonaute 超家族传统上分为 AGO 和 PIWI Argonautes。然而，通过进行系统发育分析并确定后生动物 Argonaute 超家族的选择进化压力，我们提供了证据表明在基础后生动物和原口动物之间存在三个保守的 Argonaute 谱系，即 siRNA 类 AGO、miRNA 类 AGO 和 PIWI Argonautes。此外，研究表明 siRNA 类 AGO 谱系的分子进化率很高，表明其在与病毒的军备竞赛中发挥作用，而 miRNA 类 AGOs 则显示出很强的序列保守性。有趣的是，我们还证明脊椎动物缺乏 siRNA 类 AGO 蛋白，并且脊椎动物 AGOs 的分子进化率很低。通过这种方式，我们为脊椎动物中抗病毒 siRNA 类 AGO 组的丢失提供了支持性证据，并讨论了这对脊椎动物抗病毒免疫和在这些动物中使用 RNAi 作为功能丧失工具的影响。
