Genomic Recoding Broadly Obstructs the Propagation of Horizontally Transferred Genetic Elements

Area of Science:

• Synthetic Biology
• Microbiology
• Genetics

Background:

• Horizontal gene transfer (HGT) via viruses and plasmids increases genetic diversity but can destabilize engineered organisms.
• Understanding mechanisms that limit HGT is crucial for robust synthetic biology.

Purpose of the Study:

• To investigate the impact of an alternative genetic code on the propagation of horizontally transferred genetic elements.
• To assess the potential of genomic recoding for stabilizing engineered biological systems.

Main Methods:

• Genomically recoded Escherichia coli strains lacking UAG stop codons were utilized.
• Resistance to viral infection and conjugative plasmid transfer was measured.
• Recoding of viral and plasmid genomes was performed to restore function.

Main Results:

• The alternative genetic code conferred resistance to multiple viruses and impaired conjugative plasmids.
• Recoding UAG codons in viruses and plasmids restored their infectivity and conjugative function.
• Mixed communities of cells with standard and alternative codes reduced viral titers, with observed viral adaptation over time.

Conclusions:

• Altering the genetic code is an effective strategy to broadly obstruct the propagation of horizontally transferred genetic elements.
• Genomic recoding can be employed to enhance the stability of engineered biological systems against HGT.
• This study provides a novel approach for controlling genetic element mobility in microbial communities.