A quantitative framework for characterizing the evolutionary history of mammalian gene expression
A quantitative framework for characterizing the evolutionary history of mammalian gene expression
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DOI：
10.1101/gr.237636.118
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发表时间：
2019-01-01
期刊：
影响因子：
7
通讯作者：
Regev, Aviv
中科院分区：
文献类型：
--
作者：
Chen, Jenny;Swofford, Ross;Regev, Aviv
基因的进化历史有助于预测其功能以及与表型性状的关系。虽然序列保守性通常用于破译基因功能和评估医学相关性，但缺乏从比较表达数据进行功能推断的方法。在这里，我们在17种哺乳动物的7种组织中使用RNA-seq，以表明哺乳动物的表达进化是由Ornstein-Uhlenbeck过程准确建模的，Ornstein-Uhlenbeck过程是一种常见的连续性状进化模型。我们应用这个模型来确定中性，稳定和定向选择下的表达途径。我们进一步展示了新的应用程序，这个模型来量化的程度上稳定的选择基因的表达，参数化的每个基因的最佳表达水平的分布，并检测有害的表达水平，从个别患者的表达数据。我们的工作为解释跨物种和疾病的表达数据提供了一个统计框架。
The evolutionary history of a gene helps predict its function and relationship to phenotypic traits. Although sequence conservation is commonly used to decipher gene function and assess medical relevance, methods for functional inference from comparative expression data are lacking. Here, we use RNA-seq across seven tissues from 17 mammalian species to show that expression evolution across mammals is accurately modeled by the Ornstein-Uhlenbeck process, a commonly proposed model of continuous trait evolution. We apply this model to identify expression pathways under neutral, stabilizing, and directional selection. We further demonstrate novel applications of this model to quantify the extent of stabilizing selection on a gene's expression, parameterize the distribution of each gene's optimal expression level, and detect deleterious expression levels in expression data from individual patients. Our work provides a statistical framework for interpreting expression data across species and in disease.