具有重新洗牌的分隔环境中的Natural selection
Natural selection in compartmentalized environment with reshuffling
摘要：
高通量区室化体外进化是蛋白质工程研究的一个新方向。在这些实验中，突变基因型文库随机分布并在微观隔室-乳液液滴中表达。根据每个区室的表型进行所需变体的选择。随机划分导致一小部分隔室接收多于一种基因型，使得整个过程成为组选择的实验室实施。从实践的角度来看（通常寻求有效的选择），重要的是要知道隔间平均占用率的增加对选择效率的影响。我们进行了一个理论研究这个问题的背景下，选择动态的无限非突变细分人口，随机殖民化的无限数量的补丁（车厢）在每个繁殖周期。我们在这里推导出一个更新方程的任何分布的表型和任何值的平均占有率。使用这个结果，我们证明了，对于线性加性适应度，最好的基因型仍然被选择，而不管平均占有率。此外，选择过程对每个隔室中存在多个基因型具有显著的弹性，并且在高值下与平均占有率大致成反比地减慢。我们将结果扩展到更一般的表达式，包括非加性和非线性拟合，以及非泊松分布之间的车厢。我们的结论也可能适用于自然的遗传区室化复制因子，如病毒或早期的反式作用RNA复制因子。
英文摘要：
The emerging field of high-throughput compartmentalized in vitro evolution is a promising new approach to protein engineering. In these experiments, libraries of mutant genotypes are randomly distributed and expressed in microscopic compartments - droplets of an emulsion. The selection of desirable variants is performed according to the phenotype of each compartment. The random partitioning leads to a fraction of compartments receiving more than one genotype making the whole process a lab implementation of the group selection. From a practical point of view (where efficient selection is typically sought), it is important to know the impact of the increase in the mean occupancy of compartments on the selection efficiency. We carried out a theoretical investigation of this problem in the context of selection dynamics for an infinite non-mutating subdivided population that randomly colonizes an infinite number of patches (compartments) at each reproduction cycle. We derive here an update equation for any distribution of phenotypes and any value of the mean occupancy. Using this result, we demonstrate that, for the linear additive fitness, the best genotype is still selected regardless of the mean occupancy. Furthermore, the selection process is remarkably resilient to the presence of multiple genotypes per compartments, and slows down approximately inversely proportional to the mean occupancy at high values. We extend out results to more general expressions that cover nonadditive and non-linear fitnesses, as well non-Poissonian distribution among compartments. Our conclusions may also apply to natural genetic compartmentalized replicators, such as viruses or early trans-acting RNA replicators.
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