Center for Computational Biology and Bioinformatics, Institute for Cellular and Molecular Biology, University of Texas, Austin, Texas 78712, USA.
Genetics. 2011 Jun;188(2):479-88. doi: 10.1534/genetics.111.128025. Epub 2011 Apr 5.
Recent work with Saccharomyces cerevisiae shows a linear relationship between the evolutionary rate of sites and the relative solvent accessibility (RSA) of the corresponding residues in the folded protein. Here, we aim to develop a mathematical model that can reproduce this linear relationship. We first demonstrate that two models that both seem reasonable choices (a simple model in which selection strength correlates with RSA and a more complex model based on RSA-dependent amino acid distributions) fail to reproduce the observed relationship. We then develop a model on the basis of observed site-specific amino acid distributions and show that this model behaves appropriately. We conclude that evolutionary rates are directly linked to the distribution of amino acids at individual sites. Because of this link, any future insight into the biophysical mechanisms that determine amino acid distributions will improve our understanding of evolutionary rates.
最近对酿酒酵母的研究表明，折叠蛋白质中对应残基的进化速率与相对溶剂可及性（RSA）之间存在线性关系。在这里，我们旨在开发一种可以再现这种线性关系的数学模型。我们首先证明，两个似乎都是合理选择的模型（一个简单的模型，其中选择强度与 RSA 相关，另一个更复杂的基于 RSA 相关的氨基酸分布的模型）都无法再现观察到的关系。然后，我们基于观察到的特定位置的氨基酸分布开发了一个模型，并表明该模型表现良好。我们得出结论，进化速率与单个位置的氨基酸分布直接相关。由于这种联系，任何对决定氨基酸分布的生物物理机制的未来见解都将提高我们对进化速率的理解。
