An Experimentally Determined Evolutionary Model Dramatically Improves Phylogenetic Fit
An Experimentally Determined Evolutionary Model Dramatically Improves Phylogenetic Fit
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DOI：
10.1093/molbev/msu173
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发表时间：
2014-08-01
影响因子：
10.7
通讯作者：
Bloom, Jesse D.
中科院分区：
文献类型：
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作者：
Bloom, Jesse D.
所有现代的分子遗传学方法都需要一个基因进化的定量模型。不幸的是，现有的进化模型并不能真实地代表控制实际序列变化的位点异质性选择。为了解决这个问题，人们尝试用大量的自由参数来扩充这些模型。在这里，我展示了一种替代方案：通过诱变，功能选择和深度测序实验确定无参数进化模型。使用这种策略，我创建了一个流感核蛋白的进化模型，它描述了基因的遗传学，远远优于现有的模型与几十个甚至几百个自由参数。新兴的高通量实验策略，如这里采用的一个提供了从根本上新的信息，有可能改变系统发育和遗传分析的灵敏度。
All modern approaches to molecular phylogenetics require a quantitative model for how genes evolve. Unfortunately, existing evolutionary models do not realistically represent the site-heterogeneous selection that governs actual sequence change. Attempts to remedy this problem have involved augmenting these models with a burgeoning number of free parameters. Here, I demonstrate an alternative: Experimental determination of a parameter-free evolutionary model via mutagenesis, functional selection, and deep sequencing. Using this strategy, I create an evolutionary model for influenza nucleoprotein that describes the gene phylogeny far better than existing models with dozens or even hundreds of free parameters. Emerging high-throughput experimental strategies such as the one employed here provide fundamentally new information that has the potential to transform the sensitivity of phylogenetic and genetic analyses.