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Suppressing evolution in genetically engineered systems through repeated supplementation
Evolutionary Applications ( IF 4.1 ) Pub Date : 2020-09-05 , DOI: 10.1111/eva.13119
Nathan C. Layman 1 , Beth M. Tuschhoff 2 , Andrew J. Basinski 2 , Christopher H. Remien 2 , James J. Bull 1 , Scott L. Nuismer 1
Affiliation  

Genetically engineered organisms are prone to evolve in response to the engineering. This evolution is often undesirable and can negatively affect the purpose of the engineering. Methods that maintain the stability of engineered genomes are therefore critical to the successful design and use of genetically engineered organisms. One potential method to limit unwanted evolution is by taking advantage of the ability of gene flow to counter local adaption, a process of supplementation. Here, we investigate the feasibility of supplementation as a mechanism to offset the evolutionary degradation of a transgene in three model systems: a bioreactor, a gene drive, and a transmissible vaccine. In each model, continual introduction from a stock is used to balance mutation and selection against the transgene. Each system has its unique features. The bioreactor system is especially tractable and has a simple answer: The level of supplementation required to maintain the transgene at a frequency urn:x-wiley:17524571:media:eva13119:eva13119-math-0001 is approximately urn:x-wiley:17524571:media:eva13119:eva13119-math-0002, where s is the selective disadvantage of the transgene. Supplementation is also feasible in the transmissible vaccine case but is probably not practical to prevent the evolution of resistance against a gene drive. We note, however, that the continual replacement of even a small fraction of a large population can be challenging, limiting the usefulness of supplementation as a means of controlling unwanted evolution.

中文翻译:

通过反复补充来抑制基因工程系统的进化

基因工程生物易于响应工程而进化。这种演变通常是不希望的,并且可能对工程的目的产生负面影响。因此,维持工程基因组稳定性的方法对于成功设计和使用基因工程生物至关重要。限制有害进化的一种潜在方法是利用基因流动的能力来抵抗局部适应(补充过程)。在这里,我们研究了补充作为抵消转基因在三个模型系统中进化降解的机制的可行性:生物反应器,基因驱动器和可传播疫苗。在每个模型中,从种群中连续引入被用来平衡针对转基因的突变和选择。每个系统都有其独特的功能。缸:x-wiley:17524571:media:eva13119:eva13119-math-0001大约为骨灰盒:x-wiley:17524571:media:eva13119:eva13119-math-0002,其中s是转基因的选择性劣势。在可传播疫苗的情况下补充也是可行的,但是对于防止对基因驱动的抗性的进化可能不可行。但是,我们注意到,即使是一小部分人口的持续替换也可能具有挑战性,限制了补充作为控制有害进化的手段的有用性。
更新日期:2020-09-05
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