从随机蛋白质池中选择的层次和极端
Hierarchy and extremes in selections from pools of randomized proteins
摘要：
变异和选择是达尔文进化论的核心原则，但将种群的多样性与其对选择的反应能力定量联系起来是一项挑战。在这里，我们在分子水平上研究这个问题的背景下，部分随机化的蛋白质选择结合到明确的目标。我们建立了几个最小的蛋白质文库，筛选他们在体外噬菌体展示和分析他们的高通量测序选择的反应。对结果的统计分析揭示了两个主要发现：第一，具有相同序列多样性但围绕不同“框架”构建的文库通常具有极大不同的响应，第二，文库内响应的分布遵循简单的比例定律。我们展示了如何一个基本的概率模型的基础上极值理论合理化这些发现。我们的研究结果具有一定的影响，设计合成蛋白质库，估计在序列空间中的功能生物分子的密度，在自然种群的多样性特征和实验研究的概念，进化性，或未来的进化潜力。
英文摘要：
Variation and selection are the core principles of Darwinian evolution, yet quantitatively relating the diversity of a population to its capacity to respond to selection is challenging. Here, we examine this problem at a molecular level in the context of populations of partially randomized proteins selected for binding to well-defined targets. We built several minimal protein libraries, screened them in vitro by phage display and analyzed their response to selection by high-throughput sequencing. A statistical analysis of the results reveals two main findings: first, libraries with same sequence diversity but built around different "frameworks" typically have vastly different responses, second, the distribution of responses within a library follows a simple scaling law. We show how an elementary probabilistic model based on extreme value theory rationalizes these findings. Our results have implications for designing synthetic protein libraries, for estimating the density of functional biomolecules in sequence space, for characterizing diversity in natural populations and for experimentally investigating the concept of evolvability, or potential for future evolution.
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