Modeling Gene Expression Evolution with an Extended Ornstein-Uhlenbeck Process Accounting for Within-Species Variation
Modeling Gene Expression Evolution with an Extended Ornstein-Uhlenbeck Process Accounting for Within-Species Variation
复制标题
DOI：
10.1093/molbev/mst190
复制
发表时间：
2014-01-01
影响因子：
10.7
通讯作者：
Nielsen, Rasmus
中科院分区：
文献类型：
--
作者：
Rohlfs, Rori V.;Harrigan, Patrick;Nielsen, Rasmus
即使在密切相关的物种之间观察到的许多表型变异也可能是由基因表达水平的差异驱动的。目前可用的可靠技术，如RNA-Seq，可以量化跨物种的表达水平，使比较研究成为可能。Ornstein-Uhlenbeck（Ornstein-Uhlenbeck）过程已经被提出来模拟基因表达进化，因为它们模拟了随机漂移和稳定选择，并且可以扩展到模拟选择机制的变化。该模型提供了一个统计框架，允许比较选择性制度的具体假设，包括随机漂移，约束漂移和表达水平的变化。这样，就可以推断出作用于基因表达水平的选择模式。我们增加了这个模型，包括物种内的表达差异，允许建模的非进化表达差异，可能是由个人的遗传，环境或技术变异。通过模拟，我们探讨了参数估计的可靠性和不同的选择性制度可以区分使用不同大小的cumbergenies使用典型的cumbergenies模型和我们的扩展模型的程度。我们发现，如果不考虑个体变异，非进化表达变异往往被误认为是强稳定选择。随着比较表达数据变得越来越可用，研究人员将表达作为主要的进化表型，本文中提出的方法越来越相关。
Much of the phenotypic variation observed between even closely related species may be driven by differences in gene expression levels. The current availability of reliable techniques like RNA-Seq, which can quantify expression levels across species, has enabled comparative studies. Ornstein-Uhlenbeck (OU) processes have been proposed to model gene expression evolution as they model both random drift and stabilizing selection and can be extended to model changes in selection regimes. The OU models provide a statistical framework that allows comparisons of specific hypotheses of selective regimes, including random drift, constrained drift, and expression level shifts. In this way, inferences may be made about the mode of selection acting on the expression level of a gene. We augment this model to include within-species expression variance, allowing for modeling of nonevolutionary expression variance that could be caused by individual genetic, environmental, or technical variation. Through simulations, we explore the reliability of parameter estimates and the extent to which different selective regimes can be distinguished using phylogenies of varying size using both the typical OU model and our extended model. We find that if individual variation is not accounted for, nonevolutionary expression variation is often mistaken for strong stabilizing selection. The methods presented in this article are increasingly relevant as comparative expression data becomes more available and researchers turn to expression as a primary evolving phenotype.