Palmer William H, Obbard Darren J
Institute of Evolutionary Biology and Centre for Infection, Evolution and Immunity, University of Edinburgh, EH9 3FL UK
Institute of Evolutionary Biology and Centre for Infection, Evolution and Immunity, University of Edinburgh, EH9 3FL UK.
G3 (Bethesda). 2016 Aug 9;6(8):2563-72. doi: 10.1534/g3.116.031880.
RNA interference pathways mediate biological processes through Argonaute-family proteins, which bind small RNAs as guides to silence complementary target nucleic acids . In insects and crustaceans Argonaute-2 silences viral nucleic acids, and therefore acts as a primary effector of innate antiviral immunity. Although the function of the major Argonaute-2 domains, which are conserved across most Argonaute-family proteins, are known, many invertebrate Argonaute-2 homologs contain a glutamine-rich repeat (GRR) region of unknown function at the N-terminus . Here we combine long-read amplicon sequencing of Drosophila Genetic Reference Panel (DGRP) lines with publicly available sequence data from many insect species to show that this region evolves extremely rapidly and is hyper-variable within species. We identify distinct GRR haplotype groups in Drosophila melanogaster, and suggest that one of these haplotype groups has recently risen to high frequency in a North American population. Finally, we use published data from genome-wide association studies of viral resistance in D. melanogaster to test whether GRR haplotypes are associated with survival after virus challenge. We find a marginally significant association with survival after challenge with Drosophila C Virus in the DGRP, but we were unable to replicate this finding using lines from the Drosophila Synthetic Population Resource panel.
RNA干扰途径通过AGO蛋白介导生物学过程，AGO蛋白结合小RNA作为引导来沉默互补的靶核酸。在昆虫和甲壳类动物中，AGO2可沉默病毒核酸，因此是先天性抗病毒免疫的主要效应因子。尽管大多数AGO家族蛋白中保守的主要AGO2结构域的功能是已知的，但许多无脊椎动物AGO2同源物在N端含有一个功能未知的富含谷氨酰胺的重复序列（GRR）区域。在这里，我们将果蝇遗传参考面板（DGRP）品系的长读长扩增子测序与来自许多昆虫物种的公开可用序列数据相结合，以表明该区域进化极其迅速，并且在物种内具有高度变异性。我们在黑腹果蝇中鉴定出不同的GRR单倍型组，并表明这些单倍型组之一最近在北美种群中升至高频。最后，我们使用来自黑腹果蝇病毒抗性全基因组关联研究的已发表数据来测试GRR单倍型是否与病毒攻击后的存活相关。我们发现DGRP中与果蝇C病毒攻击后的存活存在微弱的显著关联，但我们无法使用果蝇合成种群资源面板中的品系重复这一发现。
