DePristo Mark A, Weinreich Daniel M, Hartl Daniel L
Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Nat Rev Genet. 2005 Sep;6(9):678-87. doi: 10.1038/nrg1672.
Proteins are finicky molecules; they are barely stable and are prone to aggregate, but they must function in a crowded environment that is full of degradative enzymes bent on their destruction. It is no surprise that many common diseases are due to missense mutations that affect protein stability and aggregation. Here we review the literature on biophysics as it relates to molecular evolution, focusing on how protein stability and aggregation affect organismal fitness. We then advance a biophysical model of protein evolution that helps us to understand phenomena that range from the dynamics of molecular adaptation to the clock-like rate of protein evolution.
蛋白质是挑剔的分子；它们几乎不稳定且易于聚集，但它们必须在充满致力于破坏它们的降解酶的拥挤环境中发挥作用。许多常见疾病是由影响蛋白质稳定性和聚集的错义突变引起的，这并不奇怪。在这里，我们回顾了与分子进化相关的生物物理学文献，重点关注蛋白质稳定性和聚集如何影响生物体的适应性。然后，我们提出了一个蛋白质进化的生物物理模型，这有助于我们理解从分子适应的动态到蛋白质进化的时钟般速率等一系列现象。
