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Adaptive evolution among cytoplasmic piRNA proteins leads to decreased genomic auto-immunity.
PLOS Genetics ( IF 4.5 ) Pub Date : 2020-06-11 , DOI: 10.1371/journal.pgen.1008861
Luyang Wang 1 , Daniel A Barbash 2 , Erin S Kelleher 1
Affiliation  

In metazoan germlines, the piRNA pathway acts as a genomic immune system, employing small RNA-mediated silencing to defend host DNA from the harmful effects of transposable elements (TEs). Expression of genomic TEs is proposed to initiate self regulation by increasing the production of repressive piRNAs, thereby “adapting” piRNA-mediated control to the most active TE families. Surprisingly, however, piRNA pathway proteins, which execute piRNA biogenesis and enforce silencing of targeted sequences, evolve rapidly and adaptively in animals. If TE silencing is ensured through piRNA biogenesis, what necessitates changes in piRNA pathway proteins? Here we used interspecific complementation to test for functional differences between Drosophila melanogaster and D. simulans alleles of three adaptively evolving piRNA pathway proteins: Armitage, Aubergine and Spindle-E. In contrast to piRNA-mediated transcriptional regulators examined in previous studies, these three proteins have cytoplasmic functions in piRNA maturation and post-transcriptional silencing. Across all three proteins we observed interspecific divergence in the regulation of only a handful of TE families, which were more robustly silenced by the heterospecific piRNA pathway protein. This unexpected result suggests that unlike transcriptional regulators, positive selection has not acted on cytoplasmic piRNA effector proteins to enhance their function in TE repression. Rather, TEs may evolve to “escape” silencing by host proteins. We further discovered that D. simulans alleles of aub and armi exhibit enhanced off-target effects on host transcripts in a D. melanogaster background, as well as modest reductions in the efficiency of piRNA biogenesis, suggesting that promiscuous binding of D. simulans Aub and Armi proteins to host transcripts reduces their participation in piRNA production. Avoidance of genomic auto-immunity may therefore be a critical target of selection. Our observations suggest that piRNA effector proteins are subject to an evolutionary trade-off between defending the host genome from the harmful effect of TEs while also minimizing collateral damage to host genes.



中文翻译:

细胞质piRNA蛋白之间的适应性进化导致基因组自身免疫性降低。

在后生种系中,piRNA途径充当基因组免疫系统,利用小RNA介导的沉默来保护宿主DNA免受转座因子(TEs)的有害影响。有人提出基因组TE的表达通过增加抑制性piRNA的产生来启动自我调节,从而使piRNA介导的控制“适应”最活跃的TE家族。然而,令人惊讶的是,执行piRNA生物发生并强制靶向序列沉默的piRNA途径蛋白在动物中迅速适应性地进化。如果通过piRNA生物发生确保TE沉默,那么piRNA途径蛋白发生变化的必要条件是什么?在这里,我们用种间互补,以测试之间的功能差异果蝇d模仿者三种自适应进化的piRNA途径蛋白的等位基因:Armitage,茄子和Spindle-E。与先前研究中检测到的piRNA介导的转录调节因子相比,这三种蛋白质在piRNA成熟和转录后沉默中具有细胞质功能。在所有这三种蛋白中,我们仅在少数TE家族的调控中观察到种间差异,而异种piRNA途径蛋白则更能使它们沉默。这一出乎意料的结果表明,与转录调节因子不同,阳性选择并未作用于细胞质piRNA效应蛋白来增强其在TE抑制中的功能。相反,TE可能进化为通过宿主蛋白“逃避”沉默。我们进一步发现,d的类似物等位基因奥夫ARMI表现出增强的对在宿主转录物的脱靶效应d黑色素瘤的背景以及piRNA生物合成效率的适度降低,表明D的混杂结合。宿主转录本的类似物Aub和Armi蛋白减少了它们对piRNA产生的参与。因此,避免基因组自身免疫可能是选择的关键目标。我们的观察结果表明,piRNA效应蛋白需要在保护宿主基因组免受TE的有害影响的同时,也要最小化对宿主基因的附带损害之间的进化权衡。

更新日期:2020-06-11
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