Scripts from: Controlling evolution in genetically engineered systems through repeated introduction

Genetically engineered transgenes evolve in the same way as other genetic material. However, evolution in engineered genes is often undesirable and can negatively affect their stability, frequency, and efficacy over time. 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.

Methods
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