An experimentally informed evolutionary model improves phylogenetic fit to divergent lactamase homologs.
An experimentally informed evolutionary model improves phylogenetic fit to divergent lactamase homologs.
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DOI：
10.1093/molbev/msu220
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发表时间：
2014-10
影响因子：
10.7
通讯作者：
Bloom JD
中科院分区：
文献类型：
--
作者：
Bloom JD
分子数据的系统发育分析需要序列如何进化的定量模型。传统上，控制序列进化的位点特异性选择的细节是先验未知的，使得创建充分捕获不同位点选择异质性的进化模型具有挑战性。然而，高通量实验的最新进展使得量化所有单个突变对基因功能的影响成为可能。我之前已经证明，这种高通量实验可以与潜在突变率的知识相结合，以创建一个无参数的进化模型，该模型描述流感核蛋白的进化远远优于常用的现有模型。在这里，我通过显示已发表的关于TEM-1 β-内酰胺酶的实验数据（Firnberg E，Labonte JW，Gray JJ，Ostermeier M. 2014.一个基因的适应性景观的全面，高分辨率的地图。分子生物学评价31：1581-1592）可以与几个突变率参数组合以创建比大多数常见的现有模型更好地描述β-内酰胺酶突变基因的进化模型。这种实验性的进化模型甚至对于与作为实验研究对象的TEM-1亲本基本上分歧（在蛋白质水平上约35%分歧）的同源物也是上级的。这些结果表明，实验测量可以告知系统发育进化模型，适用于跨越大范围的序列分歧的同系物。
Phylogenetic analyses of molecular data require a quantitative model for how sequences evolve. Traditionally, the details of the site-specific selection that governs sequence evolution are not known a priori, making it challenging to create evolutionary models that adequately capture the heterogeneity of selection at different sites. However, recent advances in high-throughput experiments have made it possible to quantify the effects of all single mutations on gene function. I have previously shown that such high-throughput experiments can be combined with knowledge of underlying mutation rates to create a parameter-free evolutionary model that describes the phylogeny of influenza nucleoprotein far better than commonly used existing models. Here, I extend this work by showing that published experimental data on TEM-1 beta-lactamase (Firnberg E, Labonte JW, Gray JJ, Ostermeier M. 2014. A comprehensive, high-resolution map of a gene’s fitness landscape. Mol Biol Evol. 31:1581–1592) can be combined with a few mutation rate parameters to create an evolutionary model that describes beta-lactamase phylogenies much better than most common existing models. This experimentally informed evolutionary model is superior even for homologs that are substantially diverged (about 35% divergence at the protein level) from the TEM-1 parent that was the subject of the experimental study. These results suggest that experimental measurements can inform phylogenetic evolutionary models that are applicable to homologs that span a substantial range of sequence divergence.
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影响因子：
4.5
作者：
Hershberg R;Petrov DA
通讯作者：
Petrov DA
影响因子：
10.7
作者：
Kosiol, Carolin;Holmes, Ian;Goldman, Nick
通讯作者：
Goldman, Nick
影响因子：
10.7
作者：
Bloom, Jesse D.
通讯作者：
Bloom, Jesse D.
影响因子：
10.7
作者：
Firnberg E;Labonte JW;Gray JJ;Ostermeier M
通讯作者：
Ostermeier M
影响因子：
6.5
作者：
HUELSENBECK, JP;HILLIS, DM
通讯作者：
HILLIS, DM