Background The bulk of variability in mRNA sequence arises due to mutation—change in DNA sequence which is heritable if it occurs in the germline. However, variation in mRNA can also be achieved by post-transcriptional modification including mRNA editing, changes in mRNA nucleotide sequence that mimic the effect of mutations. Such modifications are not inherited directly; however, as the processes affecting them are encoded in the genome, they have a heritable component, and therefore can be shaped by selection. In soft-bodied cephalopods, adenine-to-inosine RNA editing is very frequent, and much of it occurs at nonsynonymous sites, affecting the sequence of the encoded protein. Methods We study selection regimes at coleoid A-to-I editing sites, estimate the prevalence of positive selection, and analyze interdependencies between the editing level and contextual characteristics of editing site. Results Here, we show that mRNA editing of individual nonsynonymous sites in cephalopods originates in evolution through substitutions at regions adjacent to these sites. As such substitutions mimic the effect of the substitution at the edited site itself, we hypothesize that they are favored by selection if the inosine is selectively advantageous to adenine at the edited position. Consistent with this hypothesis, we show that edited adenines are more frequently substituted with guanine, an informational analog of inosine, in the course of evolution than their unedited counterparts, and for heavily edited adenines, these transitions are favored by positive selection. Our study shows that coleoid editing sites may enhance adaptation, which, together with recent observations on Drosophila and human editing sites, points at a general role of RNA editing in the molecular evolution of metazoans.

中文翻译：

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软体头足类动物 mRNA 编辑位点的适应性进化


背景 mRNA 序列的大部分变异性是由于 DNA 序列的突变而产生的，如果这种突变发生在种系中，则这种变化是可遗传的。然而，mRNA 的变异也可以通过转录后修饰来实现，包括 mRNA 编辑、模仿突变效应的 mRNA 核苷酸序列的改变。此类修改不会直接继承；然而，由于影响它们的过程是在基因组中编码的，因此它们具有可遗传的成分，因此可以通过选择来塑造。在软体头足类动物中，腺嘌呤到肌苷的 RNA 编辑非常频繁，其中大部分发生在非同义位点，影响编码蛋白质的序列。方法 我们研究胶体 A 到 I 编辑位点的选择机制，估计正选择的发生率，并分析编辑水平和编辑位点的上下文特征之间的相互依赖性。结果在这里，我们表明，头足类动物中各个非同义位点的 mRNA 编辑起源于进化，通过这些位点邻近区域的替换。由于此类取代模仿了编辑位点本身的取代效果，因此我们假设，如果肌苷在编辑位置上选择性地对腺嘌呤有利，那么它们会受到选择的青睐。与这一假设一致，我们表明，在进化过程中，编辑的腺嘌呤比未编辑的腺嘌呤更频繁地被鸟嘌呤（肌苷的信息类似物）取代，并且对于大量编辑的腺嘌呤，这些转变受到正选择的青睐。 我们的研究表明胶状体编辑位点可能会增强适应能力，这与最近对果蝇和人类编辑位点的观察一起表明了 RNA 编辑在后生动物分子进化中的一般作用。