A probabilistic model for the evolution of RNA structure
A probabilistic model for the evolution of RNA structure
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DOI：
10.1186/1471-2105-5-166
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发表时间：
2004-10-26
影响因子：
3
通讯作者：
Holmes, I
中科院分区：
文献类型：
--
作者：
Holmes, I
背景资料：为了在多基因组数据集中发现和比对非编码RNA基因和顺式调控元件，能够导出多序列随机文法是有用的（以及因此的多个比对算法）系统地，从关于各种随机突变事件及其速率的假设开始。在这里，我们考虑一个高度简化的RNA进化模型，称为“TKF 91结构树”。（遵循Thorne，Kishino和Felsenstein的1991年具有插入缺失的序列进化模型），我们已经实现了成对比对，作为这种方法的原理证明。该模型，它的优点和它的缺点进行了讨论，参考四个例子的功能ncRNA序列：核糖开关（鸟嘌呤），一个zipcode（纳米），剪接因子（U4）和核酶（RNase P）。正如我们对后验概率矩阵的可视化所示，所选的例子说明了自然选择的三种不同特征，它们是ncRNA的高度特征：（i）协调碱基对取代，（ii）协调碱基对插入缺失和（iii）全茎插入缺失。虽然所有三种类型的突变“事件”都内置到我们的模型中，但发现（i）和（ii）类型的事件比（iii）类型的事件更好地建模。尽管如此，我们假设从模型的成对比对的性能，它将形成一个足够的基础上的原型多重比对和genefinding工具。
Background: For the purposes of finding and aligning noncoding RNA gene- and cis-regulatory elements in multiple-genome datasets, it is useful to be able to derive multi-sequence stochastic grammars ( and hence multiple alignment algorithms) systematically, starting from hypotheses about the various kinds of random mutation event and their rates.Results: Here, we consider a highly simplified evolutionary model for RNA, called "The TKF91 Structure Tree" (following Thorne, Kishino and Felsenstein's 1991 model of sequence evolution with indels), which we have implemented for pairwise alignment as proof of principle for such an approach. The model, its strengths and its weaknesses are discussed with reference to four examples of functional ncRNA sequences: a riboswitch (guanine), a zipcode ( nanos), a splicing factor (U4) and a ribozyme (RNase P). As shown by our visualisations of posterior probability matrices, the selected examples illustrate three different signatures of natural selection that are highly characteristic of ncRNA: (i) co-ordinated basepair substitutions, (ii) co-ordinated basepair indels and (iii) whole-stem indels.Conclusions: Although all three types of mutation "event" are built into our model, events of type ( i) and ( ii) are found to be better modeled than events of type ( iii). Nevertheless, we hypothesise from the model's performance on pairwise alignments that it would form an adequate basis for a prototype multiple alignment and genefinding tool.