Indel-Seq-Gen: A new protein family simulator incorporating domains, motifs, and indels
Indel-Seq-Gen: A new protein family simulator incorporating domains, motifs, and indels
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DOI：
10.1093/molbev/msl195
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发表时间：
2007-03-01
影响因子：
10.7
通讯作者：
Moriyama, Etsuko N.
中科院分区：
文献类型：
--
作者：
Strope, Cory L.;Scott, Stephen D.;Moriyama, Etsuko N.
重建蛋白质序列的进化历史将有助于更好地理解蛋白质超家族的分化机制及其功能。长期蛋白质进化通常包括动态变化，例如插入、缺失和结构域改组。这种动态变化使得重建蛋白质序列进化变得困难，并影响分子进化方法的准确性，如多重比对和系统发育方法。不幸的是，目前可用的模拟方法不够灵活，不允许生物学上真实的动态蛋白质序列进化。我们介绍了一种新的方法，indel-Seq-Gen（iSG），它可以模拟真实的蛋白质序列的插入和缺失（indels）的进化过程。与其他模拟方法不同，iSG允许用户根据不同的进化参数模拟多个序列，这对于生成具有多个结构域的真实蛋白质家族是必要的。iSG跟踪所有进化事件，包括插入缺失，并输出模拟序列的“真实”多重比对。iSG还可以通过允许使用多个相关根序列来生成更大的序列空间。通过所有这些功能，iSG可以用于测试例如多重比对方法、系统发育方法、进化假设、祖先蛋白质重构方法和蛋白质家族分类方法的准确性。我们通过模拟G蛋白偶联受体和脂质运载蛋白家族的进化，经验性地评估了iSG对目前可用方法的性能。我们研究了它们的真实多重比对，跨膜区和β链的重建，以及使用模拟序列对蛋白质数据库进行相似性搜索的结果。我们还提出了一个例子，使用iSG检查系统发育重建是如何受到高indel率的影响。
Reconstructing the evolutionary history of protein sequences will provide a better understanding of divergence mechanisms of protein superfamilies and their functions. Long-term protein evolution often includes dynamic changes such as insertion, deletion, and domain shuffling. Such dynamic changes make reconstructing protein sequence evolution difficult and affect the accuracy of molecular evolutionary methods, such as multiple alignments and phylogenetic methods. Unfortunately, currently available simulation methods are not sufficiently flexible and do not allow biologically realistic dynamic protein sequence evolution. We introduce a new method, indel-Seq-Gen (iSG), that can simulate realistic evolutionary processes of protein sequences with insertions and deletions (indels). Unlike other simulation methods, iSG allows the user to simulate multiple subsequences according to different evolutionary parameters, which is necessary for generating realistic protein families with multiple domains. iSG tracks all evolutionary events including indels and outputs the "true" multiple alignment of the simulated sequences. iSG can also generate a larger sequence space by allowing the use of multiple related root sequences. With all these functions, iSG can be used to test the accuracy of, for example, multiple alignment methods, phylogenetic methods, evolutionary hypotheses, ancestral protein reconstruction methods, and protein family classification methods. We empirically evaluated the performance of iSG against currently available methods by simulating the evolution of the G protein-coupled receptor and lipocalin protein families. We examined their true multiple alignments, reconstruction of the transmembrane regions and beta-strands, and the results of similarity search against a protein database using the simulated sequences. We also presented an example of using iSG for examining how phylogenetic reconstruction is affected by high indel rates.