Neutral Evolution of Robustness in Drosophila microRNA Precursors
Neutral Evolution of Robustness in Drosophila microRNA Precursors
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DOI：
10.1093/molbev/msr029
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发表时间：
2011-07-01
影响因子：
10.7
通讯作者：
Azevedo, Ricardo B. R.
中科院分区：
文献类型：
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作者：
Price, Nicholas;Cartwright, Reed A.;Azevedo, Ricardo B. R.
突变稳健性描述了在突变面前表型保持不变的程度。理论预测，突变稳健性的直接选择的强度最多是有害突变率的大小。就核酸序列而言，只有在具有高有害突变率和大种群规模的生物体中的长序列才有望进化出突变鲁棒性。令人惊讶的是，最近的研究得出结论，不符合这些条件的分子-多细胞真核生物的microRNA前体（pre-miRNAs）-显示出突变和/或环境鲁棒性的选择迹象。为了解决理论和这些研究之间的明显分歧，我们重建了果蝇pre-miRNAs的进化历史，并将每个序列的鲁棒性与其重建的祖先进行了比较。此外，我们通过模拟在不同的进化假设下的pre-miRNA进化的“磁带重放”，并将这些替代历史与实际历史进行比较。我们发现果蝇pre-miRNAs在强烈的纯化选择下进化，以对抗二级结构的变化。与先前的说法相反，没有证据表明这些RNA是通过直接或一致选择形成的，以获得任何形式的鲁棒性。相反，果蝇pre-miRNA的高鲁棒性似乎主要是内在的，并且可能是功能结构选择的结果。
Mutational robustness describes the extent to which a phenotype remains unchanged in the face of mutations. Theory predicts that the strength of direct selection for mutational robustness is at most the magnitude of the rate of deleterious mutation. As far as nucleic acid sequences are concerned, only long sequences in organisms with high deleterious mutation rates and large population sizes are expected to evolve mutational robustness. Surprisingly, recent studies have concluded that molecules that meet none of these conditions-the microRNA precursors (pre-miRNAs) of multicellular eukaryotes-show signs of selection for mutational and/or environmental robustness. To resolve the apparent disagreement between theory and these studies, we have reconstructed the evolutionary history of Drosophila pre-miRNAs and compared the robustness of each sequence to that of its reconstructed ancestor. In addition, we "replayed the tape" of pre-miRNA evolution via simulation under different evolutionary assumptions and compared these alternative histories with the actual one. We found that Drosophila pre-miRNAs have evolved under strong purifying selection against changes in secondary structure. Contrary to earlier claims, there is no evidence that these RNAs have been shaped by either direct or congruent selection for any kind of robustness. Instead, the high robustness of Drosophila pre-miRNAs appears to be mostly intrinsic and likely a consequence of selection for functional structures.