Origin and development of oligoadenylate synthetase immune system
Origin and development of oligoadenylate synthetase immune system
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寡腺苷酸合成酶免疫系统的起源和发展
DOI：
10.1186/s12862-018-1315-x
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发表时间：
2018-12-27
影响因子：
3.4
通讯作者：
Huang, Yinhua
中科院分区：
文献类型：
--
作者：
Hu, Jiaxiang;Wang, Xiaoxue;Huang, Yinhua
研究背景寡腺苷酸合成酶（Oligoadenylate synthetases，OASs）广泛分布于海绵、鱼类、爬行动物、鸟类和哺乳动物等后生动物中，其成员数在1 ~ 12个之间，变异较大。在双链RNA（dsRNA）结合后，禽类和哺乳动物OAS产生第二信使2 - 5 '-连接的寡腺苷酸（2-5A），其激活核糖核酸酶L（RNaseL）并阻断病毒复制。然而，后生动物如何塑造他们的OAS剧目，以保持进化平衡，病毒感染在很大程度上是未知的。我们进行了全面的系统发育和功能分析的OAS基因从进化上较低到较高的后生动物，以证明如何的OAS剧目开发了抗病毒活性和多样化的functions.ResultsAncient后生动物港的OAS基因，但缺乏上游和下游基因的OAS相关的途径，表明古老的OAS是不是干扰素诱导的基因参与先天免疫系统。与古后生动物（即海绵）的OAS相比，高等后生动物的相应OAS在OAS/dsRNA相互作用界面上呈现出越来越多的碱性残基。这种碱性残基的增加可能会提高它们与dsRNA的结合亲和力。此外，活性口袋中的功能残基的突变可能导致高级后生动物OAS失去产生3 - 5 '-连接的寡腺苷酸（3-5A）的能力并转化为特异性2-5A合成酶的事实。此外，我们发现，多轮的基因重复和域耦合事件发生在OAS家庭和突变的功能关键位点观察到在大多数新的OAS members.ConclusionsWe提出了一个模型的OAS成员的扩展，并提供了全面的证据，随后的新功能化和亚功能化。这些结果为探讨古老OAS基因向宿主防御基因的进化过渡奠定了基础，也为探索OAS基因家族的未知功能提供了重要信息。
BackgroundOligoadenylate synthetases (OASs) are widely distributed in Metazoa including sponges, fish, reptiles, birds and mammals and show large variation, with one to twelve members in any given species. Upon double-stranded RNA (dsRNA) binding, avian and mammalian OASs generate the second messenger 2'-5'-linked oligoadenylate (2-5A), which activates ribonuclease L (RNaseL) and blocks viral replication. However, how Metazoa shape their OAS repertoires to keep evolutionary balance to virus infection is largely unknown. We performed comprehensive phylogenetic and functional analyses of OAS genes from evolutionarily lower to higher Metazoa to demonstrate how the OAS repertoires have developed anti-viral activity and diversified their functions.ResultsAncient Metazoa harbor OAS genes, but lack both upstream and downstream genes of the OAS-related pathways, indicating that ancient OASs are not interferon-induced genes involved in the innate immune system. Compared to OASs of ancient Metazoa (i.e. sponge), the corresponding ones of higher Metazoa present an increasing number of basic residues on the OAS/dsRNA interaction interface. Such an increase of basic residues might improve their binding affinity to dsRNA. Moreover, mutations of functional residues in the active pocket might lead to the fact that higher Metazoan OASs lose the ability to produce 3'-5'-linked oligoadenylate (3-5A) and turn into specific 2-5A synthetases. In addition, we found that multiple rounds of gene duplication and domain coupling events occurred in the OAS family and mutations at functionally critical sites were observed in most new OAS members.ConclusionsWe propose a model for the expansion of OAS members and provide comprehensive evidence of subsequent neo-functionalization and sub-functionalization. Our observations lay the foundation for interrogating the evolutionary transition of ancient OAS genes to host defense genes and provide important information for exploring the unknown function of the OAS gene family.