Suppressing evolution in genetically engineered systems through repeated supplementation

Area of Science:

• Genetics
• Evolutionary Biology
• Synthetic Biology

Background:

• Genetically engineered organisms can evolve, potentially compromising their intended function.
• Maintaining the stability of engineered genomes is crucial for the successful application of genetic engineering.
• Gene flow, through supplementation, offers a potential strategy to counteract unwanted evolutionary changes.

Purpose of the Study:

• To investigate the feasibility of supplementation as a method to prevent the evolutionary degradation of transgenes.
• To assess the effectiveness of supplementation across three distinct model systems: a bioreactor, a gene drive, and a transmissible vaccine.

Main Methods:

• Modeling the impact of continuous gene flow from a stock population to balance mutation and selection pressures.
• Analyzing three distinct systems: a bioreactor, a gene drive, and a transmissible vaccine.
• Calculating the required supplementation levels to maintain transgene frequency in a bioreactor system.

Main Results:

• Supplementation is a viable strategy for maintaining transgenes in bioreactor systems, with required levels dependent on the selective disadvantage (s).
• The transmissible vaccine model also shows feasibility for supplementation.
• Supplementation is likely impractical for preventing resistance evolution in gene drive systems due to challenges in replacing even small fractions of large populations.

Conclusions:

• Supplementation can be an effective tool for stabilizing engineered gene frequencies in certain contexts, like bioreactors and vaccines.
• The practical implementation of supplementation is limited by population size and the feasibility of continuous genetic material replacement.
• Further research may be needed to optimize supplementation strategies for complex systems like gene drives.