Epistatic contributions promote the unification of incompatible models of neutral molecular evolution
Epistatic contributions promote the unification of incompatible models of neutral molecular evolution
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DOI：
10.1073/pnas.1913071117
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发表时间：
2020-03-17
影响因子：
11.1
通讯作者：
Morcos, Faruck
中科院分区：
文献类型：
--
作者：
de la Paz, Jose Alberto;Nartey, Charisse M.;Morcos, Faruck
我们引入了氨基酸序列进化模型，该模型解释了上位相互作用引起的真实序列的统计行为。我们的模型动力学基于使用直接耦合分析方法分析的多个序列比对得出的参数。已知的统计特性，例如过度分散、异速性和跨位点的伽玛分布率，被证明是该模型的新兴特性，同时与中性进化理论一致，从而统一了先前脱节的序列进化模型的观察结果。位点限制和异位性之间的关系通过跟踪位点的有效字母动态来表征。我们还观察到在我们的模拟下经历进化的序列的适应性发生进化斯托克斯转变。通过分析一些蛋白质的结构信息，我们证实最强的斯托克斯位移来自于生化重要区域附近网络中物理相互作用的位点。讨论了在分子钟背景下实施我们的模型的观点。
We introduce a model of amino acid sequence evolution that accounts for the statistical behavior of real sequences induced by epistatic interactions. We base the model dynamics on parameters derived from multiple sequence alignments analyzed by using direct coupling analysis methodology. Known statistical properties such as overdispersion, heterotachy, and gamma-distributed rate-across-sites are shown to be emergent properties of this model while being consistent with neutral evolution theory, thereby unifying observations from previously disjointed evolutionary models of sequences. The relationship between site restriction and heterotachy is characterized by tracking the effective alphabet dynamics of sites. We also observe an evolutionary Stokes shift in the fitness of sequences that have undergone evolution under our simulation. By analyzing the structural information of some proteins, we corroborate that the strongest Stokes shifts derive from sites that physically interact in networks near biochemically important regions. Perspectives on the implementation of our model in the context of the molecular clock are discussed.