Methods for measuring the evolutionary stability of engineered genomes to improve their longevity.
Methods for measuring the evolutionary stability of engineered genomes to improve their longevity.
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DOI：
10.1093/synbio/ysab018
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Bull JJ
中科院分区：
文献类型：
--
作者：
Nuismer SL;C Layman N;Redwood AJ;Chan B;Bull JJ
不同的应用依赖于工程微生物携带和表达外源转基因。这种经过改造的行李很少有益于微生物，因此当微生物繁殖时，很容易迅速丧失进化能力。对于其中转基因必须维持延长的生长期的应用，减慢转基因进化的速率是关键的，并且可以通过降低突变速率或选择强度来实现。因为通过改变这些量实现的益处通常不相等，所以重要的是要知道哪一个将对工程的进化半衰期产生最大的改善。在这里，我们提供了一种方法，用于联合估计转基因丢失的突变率和有利于这些无转基因的回复突变个体的选择强度。该方法需要来自连续转移实验的数据，其中定期监测工程基因组的频率。开发简单的数学模型，使用这些估计值来预测工程转基因的半衰期，并提供突变和选择的改变将如何影响寿命的定量预测。估计方法和预测工具已被实现为一个交互式的Web应用程序，MuSe。
Diverse applications rely on engineering microbes to carry and express foreign transgenes. This engineered baggage rarely benefits the microbe and is thus prone to rapid evolutionary loss when the microbe is propagated. For applications where a transgene must be maintained for extended periods of growth, slowing the rate of transgene evolution is critical and can be achieved by reducing either the rate of mutation or the strength of selection. Because the benefits realized by changing these quantities will not usually be equal, it is important to know which will yield the greatest improvement to the evolutionary half-life of the engineering. Here, we provide a method for jointly estimating the mutation rate of transgene loss and the strength of selection favoring these transgene-free, revertant individuals. The method requires data from serial transfer experiments in which the frequency of engineered genomes is monitored periodically. Simple mathematical models are developed that use these estimates to predict the half-life of the engineered transgene and provide quantitative predictions for how alterations to mutation and selection will influence longevity. The estimation method and predictive tools have been implemented as an interactive web application, MuSe.
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