Evidence of Adaptive Evolution in Wolbachia-Regulated Gene DNMT2 and Its Role in the Dipteran Immune Response and Pathogen Blocking.
Evidence of Adaptive Evolution in Wolbachia-Regulated Gene DNMT2 and Its Role in the Dipteran Immune Response and Pathogen Blocking.
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DOI：
10.3390/v13081464
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发表时间：
2021-07-27
期刊：
影响因子：
--
通讯作者：
Newton ILG
中科院分区：
文献类型：
--
作者：
Bhattacharya T;Rice DW;Crawford JM;Hardy RW;Newton ILG
真核细胞核酸甲基转移酶(MTase)蛋白是表观遗传和表观转录调控的重要中介。DNMT2属于一个保守的DNA MTase大家族，存在于许多生物体中，包括全变态昆虫，如果蝇和蚊子，它是唯一的MTase。有趣的是，尽管DNMT2被命名，但它不是一个DNA MTase，而是靶标和甲基化RNA物种。越来越多的文献表明，DNMT2介导了宿主对包括RNA病毒在内的多种病原体的免疫反应。奇怪的是，虽然DNMT2在果蝇中是抗病毒的，但它的表达促进了蚊子物种的病毒复制。因此，我们试图了解这些同源基因的不同调节、功能和进化。我们描述了果蝇特有的宿主蛋白iPod在调节果蝇DNMT2的表达和功能中的作用。这些同源基因的异源表达表明，DNMT2的S的抗病毒作用是宿主依赖的，这表明需要额外的宿主特异性因子。最后，我们识别和描述了在双翅目昆虫DNMT2进化过程中不同时间进行正选择的潜在证据。我们识别了每个正向同源基因中处于正选择状态的特定密码子，并发现它们被限制在四个不同的蛋白质结构域，这可能影响底物结合、靶标识别和独特分子间相互作用的适应。总而言之，我们的发现强调了DNMT2在双翅目昆虫中的进化，并指出了蚊子和果蝇同源物在结构、调节和功能上的差异。
Eukaryotic nucleic acid methyltransferase (MTase) proteins are essential mediators of epigenetic and epitranscriptomic regulation. DNMT2 belongs to a large, conserved family of DNA MTases found in many organisms, including holometabolous insects such as fruit flies and mosquitoes, where it is the lone MTase. Interestingly, despite its nomenclature, DNMT2 is not a DNA MTase, but instead targets and methylates RNA species. A growing body of literature suggests that DNMT2 mediates the host immune response against a wide range of pathogens, including RNA viruses. Curiously, although DNMT2 is antiviral in Drosophila, its expression promotes virus replication in mosquito species. We, therefore, sought to understand the divergent regulation, function, and evolution of these orthologs. We describe the role of the Drosophila-specific host protein IPOD in regulating the expression and function of fruit fly DNMT2. Heterologous expression of these orthologs suggests that DNMT2′s role as an antiviral is host-dependent, indicating a requirement for additional host-specific factors. Finally, we identify and describe potential evidence of positive selection at different times throughout DNMT2 evolution within dipteran insects. We identify specific codons within each ortholog that are under positive selection and find that they are restricted to four distinct protein domains, which likely influence substrate binding, target recognition, and adaptation of unique intermolecular interactions. Collectively, our findings highlight the evolution of DNMT2 in Dipteran insects and point to structural, regulatory, and functional differences between mosquito and fruit fly homologs.
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