Rorick Mary
University of Michigan, Department of Ecology and Evolutionary Biology, Ann Arbor, MI 48109-1048, United States.
Biosystems. 2012 Oct;110(1):22-33. doi: 10.1016/j.biosystems.2012.06.006. Epub 2012 Jul 13.
Modularity increases evolvability by reducing constraints on adaptation and by allowing preexisting parts to function in new contexts for novel uses. Protein evolution provides an excellent context to study the causes and consequences of biological modularity. In order to address such questions, however, an index for protein modularity is necessary. This paper proposes a simple index for protein modularity-"module density"-which is the number of evolutionarily independent modules that compose a protein divided by the number of amino acids in the protein. The decomposition of proteins into constituent modules can be accomplished by either of two classes of methods. The first class of methods relies on "suppositional" criteria to assign amino acids to modules, whereas the second class of methods relies on "coevolutionary" criteria for this task. One simple and practical method from the first class consists of approximating the number of modules in a protein as the number of regular secondary structure elements (i.e., helices and sheets). Methods based on coevolutionary criteria require more elaborate data, but they have the advantage of being able to specify modules without prior assumptions about why they exist. Given the increasing availability of datasets sampling protein mutational spectra (e.g., from comparative genomics, experimental evolution, and computational prediction), methods based on coevolutionary criteria will likely become more promising in the near future. The ability to meaningfully quantify protein modularity via simple indices has the potential to aid future efforts to understand protein evolutionary rate determinants, improve molecular evolution models and engineer novel proteins.
模块化通过减少对适应性的限制以及允许现有部件在新环境中发挥新用途来提高可进化性。蛋白质进化为研究生物模块化的原因和后果提供了一个绝佳的背景。然而，为了解决此类问题，需要一个蛋白质模块化指标。本文提出了一个简单的蛋白质模块化指标——“模块密度”，即组成蛋白质的进化上独立的模块数量除以蛋白质中的氨基酸数量。蛋白质分解为组成模块可通过两类方法中的任何一种来实现。第一类方法依靠“假设性”标准将氨基酸分配到模块中，而第二类方法依靠“共进化”标准来完成这项任务。第一类中的一种简单实用的方法是将蛋白质中的模块数量近似为规则二级结构元件（即螺旋和折叠）的数量。基于共进化标准的方法需要更详尽的数据，但它们的优势在于能够在无需事先假设模块为何存在的情况下确定模块。鉴于采样蛋白质突变谱的数据集（例如来自比较基因组学、实验进化和计算预测）越来越容易获得，基于共进化标准的方法在不久的将来可能会更有前景。通过简单指标有意义地量化蛋白质模块化的能力有可能有助于未来理解蛋白质进化速率决定因素、改进分子进化模型以及设计新型蛋白质的努力。
