Duan Yuange, Dou Shengqian, Luo Shiqi, Zhang Hong, Lu Jian
State Key Laboratory of Protein and Plant Gene Research, Center for Bioinformatics, School of Life Sciences & Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.
PLoS Genet. 2017 Mar 10;13(3):e1006648. doi: 10.1371/journal.pgen.1006648. eCollection 2017 Mar.
Adenosine-to-inosine (A-to-I) editing is hypothesized to facilitate adaptive evolution by expanding proteomic diversity through an epigenetic approach. However, it is challenging to provide evidences to support this hypothesis at the whole editome level. In this study, we systematically characterized 2,114 A-to-I RNA editing sites in female and male brains of D. melanogaster, and nearly half of these sites had events evolutionarily conserved across Drosophila species. We detected strong signatures of positive selection on the nonsynonymous editing sites in Drosophila brains, and the beneficial editing sites were significantly enriched in genes related to chemical and electrical neurotransmission. The signal of adaptation was even more pronounced for the editing sites located in X chromosome or for those commonly observed across Drosophila species. We identified a set of gene candidates (termed "PSEB" genes) that had nonsynonymous editing events favored by natural selection. We presented evidence that editing preferentially increased mutation sequence space of evolutionarily conserved genes, which supported the adaptive evolution hypothesis of editing. We found prevalent nonsynonymous editing sites that were favored by natural selection in female and male adults from five strains of D. melanogaster. We showed that temperature played a more important role than gender effect in shaping the editing levels, although the effect of temperature is relatively weaker compared to that of species effect. We also explored the relevant factors that shape the selective patterns of the global editomes. Altogether we demonstrated that abundant nonsynonymous editing sites in Drosophila brains were adaptive and maintained by natural selection during evolution. Our results shed new light on the evolutionary principles and functional consequences of RNA editing.
腺苷到次黄苷（A-to-I）编辑被认为可通过一种表观遗传方法扩大蛋白质组多样性，从而促进适应性进化。然而，在整个编辑组水平上提供证据支持这一假设具有挑战性。在本研究中，我们系统地鉴定了黑腹果蝇雌性和雄性大脑中的2114个A-to-I RNA编辑位点，其中近一半的位点在果蝇物种间具有进化保守的事件。我们在果蝇大脑的非同义编辑位点上检测到强烈的正选择信号，且有益的编辑位点在与化学和电神经传递相关的基因中显著富集。对于位于X染色体上的编辑位点或在果蝇物种中普遍观察到的编辑位点，适应信号更为明显。我们鉴定出一组具有受自然选择青睐的非同义编辑事件的基因候选物（称为“PSEB”基因）。我们提供的证据表明，编辑优先增加了进化保守基因的突变序列空间，这支持了编辑的适应性进化假说。我们在来自五株黑腹果蝇的雌性和雄性成虫中发现了普遍存在的受自然选择青睐的非同义编辑位点。我们表明，尽管温度的影响与物种影响相比相对较弱，但在塑造编辑水平方面，温度比性别效应发挥着更重要的作用。我们还探讨了影响全球编辑组选择模式的相关因素。总之，我们证明了果蝇大脑中丰富的非同义编辑位点具有适应性，并在进化过程中受到自然选择的维持。我们的结果为RNA编辑的进化原理和功能后果提供了新的见解。
