Evolutionary analysis of protein diversification: model improvement, assessment and application to real data

蛋白质在几乎所有的生物过程中都起着至关重要的作用，参与了各种各样的化学反应和物理任务。因此，在各种各样的研究学科中都有兴趣了解蛋白质功能特性的起源和演变。在蛋白质分析中一直存在两个问题：(1)估计基因序列的进化史，(2)了解随着时间的推移形成蛋白质功能的过程。在正式的统计框架内应用的蛋白质进化模型已被证明是解决这些问题的有力手段。在这项研究计划下，将采用几种不同的方法来提高蛋白质模型的真实性。我们的主要重点将是模拟氨基酸率矩阵的结构及其在基因内不同位点之间的可变性。我们将评估假设的改进对基于模型的推论的影响，如系统发育和积极选择位点的鉴定。

Proteins have an essential role to play in virtually all biological processes, participating in an extraordinarily diverse set of chemical reactions and physical tasks. Consequently, there is interest within a wide variety of research disciplines to understand the origin and evolution of the functional properties of proteins. Two problems are ever-present in the analysis of proteins: (i) estimating the evolutionary history of the gene sequences, and (ii) learning about the processes that have shaped the protein's function over time. Models of protein evolution, applied within a formal statistical framework, have proved to be a powerful means of addressing these problems. Under this research program, several different approaches will be employed to improve the realism of protein models. Our primary focus will be modeling the structure of the amino acid rate matrix and its variability among sites within a gene. We will assess the impact of putative improvements with respect to model-based inferences such as phylogenetics and the identification of positively selected sites.