The evolution and evolutionary consequences of marginal thermostability in proteins
The evolution and evolutionary consequences of marginal thermostability in proteins
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DOI：
10.1002/prot.22964
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发表时间：
2011-05-01
影响因子：
2.9
通讯作者：
Goldstein, Richard A.
中科院分区：
文献类型：
--
作者：
Goldstein, Richard A.
当我们试图在进化背景下解释生命系统的特征时，我们常常有兴趣了解某些特性是如何以及为何通过进化产生的，以及这些特性随后如何影响持续的进化过程。这一努力借助了简单的计算模型，这些模型具有自然生命系统的特性，但允许在完全透明的情况下对进化时间尺度进行模拟。我们研究了一个在选择压力下基因进化的模型，该基因编码一种在给定生长温度下处于预先指定折叠状态的蛋白质。我们观察到出现了稳定性适中的蛋白质，其稳定性远低于该模型可能达到的水平，变性温度与模拟温度相关，尽管不存在对这种边缘稳定性的选择压力。这表明，对边缘稳定蛋白质的观察，甚至是稳定性增加干扰功能的情况，都不能提供边缘稳定性是一种适应性的证据。相反，边缘稳定性是主要的不稳定突变和选择之间平衡的结果，这种平衡取决于有效种群大小。即使边缘稳定性不是一种适应性，蛋白质趋向边缘稳定性的自然倾向以及进化过程中出现的稳定性范围，可能对进化过程有重大影响。《蛋白质》2011年；79卷：1396 - 1407页。（C）2010年威利 - 利斯公司
When we seek to explain the characteristics of living systems in their evolutionary context, we are often interested in understanding how and why certain properties arose through evolution, and how these properties then affected the continuing evolutionary process. This endeavor has been assisted by the use of simple computational models that have properties characteristic of natural living systems but allow simulations over evolutionary timescales with full transparency. We examine a model of the evolution of a gene under selective pressure to code for a protein that exists in a prespecified folded state at a given growth temperature. We observe the emergence of proteins with modest stabilities far below those possible with the model, with a denaturation temperature tracking the simulation temperature, despite the absence of selective pressure for such marginal stability. This demonstrates that neither observations of marginally stable proteins, nor even instances where increased stability interferes with function, provide evidence that marginal stability is an adaptation. Instead the marginal stability is the result of a balance between predominantly destabilizing mutations and selection that shifts depending on effective population size. Even if marginal stability is not an adaptation, the natural tendency of proteins toward marginal stability, and the range of stabilities that occur during evolution, may have significant effect on the evolutionary process. Proteins 2011; 79: 1396-1407. (C) 2010 Wiley-Liss, Inc.