Relationship between protein thermodynamic constraints and variation of evolutionary rates among sites.
Relationship between protein thermodynamic constraints and variation of evolutionary rates among sites.
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DOI：
10.1088/1478-3975/12/2/025002
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发表时间：
2015-03-19
期刊：
影响因子：
2
通讯作者：
Wilke CO
中科院分区：
文献类型：
--
作者：
Echave J;Jackson EL;Wilke CO
蛋白质内位点间的进化速率差异取决于限制蛋白质进化的功能和生物物理特性。人们普遍认为，蛋白质必须能够稳定折叠才能发挥作用。然而，稳定性限制与位点间速率差异之间的关系尚未得到很好的理解。在此，我们提出了一个生物物理模型，该模型将蛋白质位点突变导致的热力学稳定性变化（ΔΔG）与这些位点在进化过程中突变积累的速率联系起来。我们发现这样一个“稳定性模型”通常表现良好，对于某些蛋白质，预测速率和实证观察速率之间的相关性高达0.75。我们还发现，我们的模型与另一种最近提出的“应力模型”具有相当的预测能力，“应力模型”根据突变体采用正确活性结构所需的多余能量（ΔΔG*）来解释位点间的进化速率差异。然而，这两种模型做出了不同的预测，对于某些蛋白质，稳定性模型优于应力模型，反之亦然。我们得出结论，稳定性和应力都会限制蛋白质中位点特异性的序列进化。
Evolutionary-rate variation among sites within proteins depends on functional and biophysical properties that constrain protein evolution. It is generally accepted that proteins must be able to fold stably in order to function. However, the relationship between stability constraints and among-sites rate variation is not well understood. Here, we present a biophysical model that links the thermodynamic stability changes due to mutations at sites in proteins (ΔΔG) to the rate at which mutations accumulate at those sites over evolutionary time. We find that such a “stability model” generally performs well, displaying correlations between predicted and empirically observed rates of up to 0.75 for some proteins. We further find that our model has comparable predictive power as does an alternative, recently proposed “stress model” that explains evolutionary-rate variation among sites in terms of the excess energy needed for mutants to adopt the correct active structure (ΔΔG*). The two models make distinct predictions, though, and for some proteins the stability model outperforms the stress model and vice versa. We conclude that both stability and stress constrain site-specific sequence evolution in proteins.
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