Suppressing evolution in genetically engineered systems through repeated supplementation.
Suppressing evolution in genetically engineered systems through repeated supplementation.
复制标题
通过反复补充抑制基因工程系统的进化。
DOI：
10.1111/eva.13119
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发表时间：
2021-03
影响因子：
4.1
通讯作者：
Nuismer SL
中科院分区：
文献类型：
--
作者：
Layman NC;Tuschhoff BM;Basinski AJ;Remien CH;Bull JJ;Nuismer SL
基因工程生物体很容易因工程而进化。这种演变通常是不受欢迎的，并且会对工程目的产生负面影响。因此，维持工程基因组稳定性的方法对于基因工程生物的成功设计和使用至关重要。限制不必要的进化的一种潜在方法是利用基因流的能力来对抗局部适应，即补充过程。在这里，我们研究了补充作为抵消转基因进化退化的机制在三个模型系统中的可行性：生物反应器、基因驱动和传染性疫苗。在每个模型中，从库存中持续引入用于平衡突变和针对转基因的选择。每个系统都有其独特的功能。生物反应器系统特别容易处理，并且有一个简单的答案：维持转基因频率所需的补充水平约为 ，其中 s 是转基因的选择性劣势。在传播疫苗的情况下补充也是可行的，但对于防止基因驱动抗性的进化可能不切实际。然而，我们注意到，即使是大量人口中的一小部分的持续替代也可能具有挑战性，限制了补充作为控制不必要的进化手段的有用性。
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 is approximately , 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.
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影响因子：
2
作者：
Edgington, Matthew P.;Alphey, Luke S.
通讯作者：
Alphey, Luke S.
DOI：
10.1007/bf02984069
发表时间：
1957-01-01
期刊：
JOUR GENETICS
影响因子：
--
作者：
HALDANE, J. B. S.
通讯作者：
HALDANE, J. B. S.
DOI：
10.1073/pnas.1718148115
发表时间：
2018-04-03
影响因子：
11.1
作者：
Chavez, Alejandro;Pruitt, Benjamin W.;Church, George M.
通讯作者：
Church, George M.
影响因子：
9.8
作者：
Bondel, Katharina B.;Kraemer, Susanne A.;Keightley, Peter D.
通讯作者：
Keightley, Peter D.
影响因子：
4.5
作者：
Hammond, Andrew M.;Kyrou, Kyros;Nolan, Tony
通讯作者：
Nolan, Tony