MIPhy: identify and quantify rapidly evolving members of large gene families.

MIPhy: identify and quantify rapidly evolving members of large gene families.
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DOI:
10.7717/peerj.4873
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发表时间:
2018
期刊:
影响因子:
2.7
通讯作者:
Wasmuth JD
Wasmuth JD
中科院分区:
生物学3区
文献类型:
--
作者:
Curran DM;Gilleard JS;Wasmuth JD

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过渡到新环境后,物种往往表现出快速的表型创新。其中一个最快的机制是复制,然后是现有基因的专业化。当这种情况发生在一个基因家族的成员身上时,它往往会留下一个可检测的谱系特异性扩张和收缩的系统发育特征。这些可以通过分析几个物种的基因家族,并确定与这些物种之间的已知关系无关的基因复制和丢失模式来确定。这种被称为系统发育不稳定性的特征以前与改变生物体采样方式和对其环境做出反应的适应有关;相反,低系统发育不稳定性以前与具有内源性功能的蛋白质有关。随着基因组水平数据的增加,有必要确定和量化系统发育不稳定性。在这里,我们提出了最小化系统发生学的不稳定性(MIPhy),一种通过量化基因进化历史的不一致性来解决这个问题的工具。MIPhy背后的动机是产生一种工具来帮助解释系统发育树。它可以预测一个基因家族的哪些成员正在适应性进化,只从基因树和物种之间的关系考虑。虽然它没有对积极选择进行任何估计,这是适应性进化的典型标志,但结果往往是一致的。我们通过准确预测哺乳动物细胞色素P450基因超家族的哪些成员代谢外源性物质和哪些代谢内源性化合物来证明MIPhy的有用性。我们的预测与人类酶的已知底物特异性非常相关。我们还分析了小杆线虫胶原蛋白基因家族,并使用MIPhy来预测在C. elegans,并表明我们的预测与现有知识相关。该软件可以从下载和安装,也可以作为在线网络工具在。
After transitioning to a new environment, species often exhibit rapid phenotypic innovation. One of the fastest mechanisms for this is duplication followed by specialization of existing genes. When this happens to a member of a gene family, it tends to leave a detectable phylogenetic signature of lineage-specific expansions and contractions. These can be identified by analyzing the gene family across several species and identifying patterns of gene duplication and loss that do not correlate with the known relationships between those species. This signature, termed phylogenetic instability, has been previously linked to adaptations that change the way an organism samples and responds to its environment; conversely, low phylogenetic instability has been previously linked to proteins with endogenous functions. With the increase in genome-level data, there is a need to identify and quantify phylogenetic instability. Here, we present Minimizing Instability in Phylogenetics (MIPhy), a tool that solves this problem by quantifying the incongruence of a gene’s evolutionary history. The motivation behind MIPhy was to produce a tool to aid in interpreting phylogenetic trees. It can predict which members of a gene family are under adaptive evolution, working only from a gene tree and the relationship between the species under consideration. While it does not conduct any estimation of positive selection—which is the typical indication of adaptive evolution—the results tend to agree. We demonstrate the usefulness of MIPhy by accurately predicting which members of the mammalian cytochrome P450 gene superfamily metabolize xenobiotics and which metabolize endogenous compounds. Our predictions correlate very well with known substrate specificities of the human enzymes. We also analyze the Caenorhabditis collagen gene family and use MIPhy to predict genes that produce an observable phenotype when knocked down in C. elegans, and show that our predictions correlate well with existing knowledge. The software can be downloaded and installed from and is also available as an online web tool at .
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