Matching of Soulmates: Coevolution of snoRNAs and Their Targets
Matching of Soulmates: Coevolution of snoRNAs and Their Targets
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DOI：
10.1093/molbev/mst209
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发表时间：
2014-02-01
影响因子：
10.7
通讯作者：
Hertel, Jana
中科院分区：
文献类型：
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作者：
Kehr, Stephanie;Bartschat, Sebastian;Hertel, Jana
核糖体和小核RNA（snRNA）包含许多修饰的核苷酸。这些修饰模式在进化过程中得以保留，甚至有可能将它们从酵母投射到人类身上。修饰位点的严格保守和rRNA和snRNA的缓慢进化与小核仁RNA（snoRNA）序列的快速进化相矛盾。为了解释这种差异，我们研究了整个脊椎动物中snoRNA及其靶位点的共同进化。为了测量和评估RNA-RNA相互作用的保守性，我们定义了相互作用保守性指数（ICI）。它将个体相互作用的质量与其在一组物种中的保守性范围结合起来，作为评估snoRNA与靶标相互作用保守性的有效措施。我们发现同源snoRNA的功能在进化上是稳定的，因此，相同snoRNA家族的成员指导等效的修饰。snoRNA序列的保守性在靶结合区域是高的，而其余序列变化显著。除了阐明相关进化的原理外，我们还能够在ICI测量的帮助下，将功能分配给以前的孤儿snoRNA，并将snoRNA作为伙伴与未分配给给定snoRNA的已知化学修饰相关联。此外，我们使用预测snoRNA功能结合序列保守性，以确定遥远的同源性。由于snoRNA序列的高整体熵，仅通过序列同源性搜索方法难以检测这种关系。
Ribosomal and small nuclear RNAs (snRNAs) comprise numerous modified nucleotides. The modification patterns are retained during evolution, making it even possible to project them from yeast onto human. The stringent conservation of modification sites and the slow evolution of rRNAs and snRNAs contradicts the rapid evolution of small nucleolar RNA (snoRNA) sequences. To explain this discrepancy, we investigated the coevolution of snoRNAs and their targeted sites throughout vertebrates. To measure and evaluate the conservation of RNA-RNA interactions, we defined the interaction conservation index (ICI). It combines the quality of individual interaction with the scope of its conservation in a set of species and serves as an efficient measure to evaluate the conservation of the interaction of snoRNA and target. We show that functions of homologous snoRNAs are evolutionarily stable, thus, members of the same snoRNA family guide equivalent modifications. The conservation of snoRNA sequences is high at target binding regions while the remaining sequence varies significantly. In addition to elucidating principles of correlated evolution, we were able, with the help of the ICI measure, to assign functions to previously orphan snoRNAs and to associate snoRNAs as partners to known chemical modifications unassigned to a given snoRNA. Furthermore, we used predictions of snoRNA functions in conjunction with sequence conservation to identify distant homologies. Because of the high overall entropy of snoRNA sequences, such relationships are hard to detect by means of sequence homology search methods alone.