Department of Ecology and Evolution, University of Chicago, Illinois 60637; email:
Department of Human Genetics, University of Chicago, Illinois 60637.
Annu Rev Biophys. 2017 May 22;46:247-269. doi: 10.1146/annurev-biophys-070816-033631. Epub 2017 Mar 15.
A central goal in biochemistry is to explain the causes of protein sequence, structure, and function. Mainstream approaches seek to rationalize sequence and structure in terms of their effects on function and to identify function's underlying determinants by comparing related proteins to each other. Although productive, both strategies suffer from intrinsic limitations that have left important aspects of many proteins unexplained. These limits can be overcome by reconstructing ancient proteins, experimentally characterizing their properties, and retracing their evolution through time. This approach has proven to be a powerful means for discovering how historical changes in sequence produced the functions, structures, and other physical/chemical characteristics of modern proteins. It has also illuminated whether protein features evolved because of functional optimization, historical constraint, or blind chance. Here we review recent studies employing ancestral protein reconstruction and show how they have produced new knowledge not only of molecular evolutionary processes but also of the underlying determinants of modern proteins' physical, chemical, and biological properties.
生物化学的一个核心目标是解释蛋白质序列、结构和功能的成因。主流方法试图根据对功能的影响来合理化序列和结构，并通过相互比较相关蛋白质来确定功能的潜在决定因素。尽管这两种策略都富有成效，但它们都存在内在的局限性，导致许多蛋白质的重要方面仍未得到解释。通过重建古老的蛋白质，实验性地描述它们的性质，并通过时间回溯它们的进化，可以克服这些限制。这种方法已被证明是一种强大的手段，可以发现序列的历史变化如何产生现代蛋白质的功能、结构和其他物理/化学特性。它还阐明了蛋白质特征是由于功能优化、历史约束还是盲目机会而进化的。在这里，我们回顾了最近采用祖先蛋白重建的研究，并展示了它们如何不仅产生了分子进化过程的新知识，而且还产生了现代蛋白质物理、化学和生物学特性的潜在决定因素的新知识。
