Cell Systems
Volume 3, Issue 2, 24 August 2016, Pages 199-207
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Genomic Recoding Broadly Obstructs the Propagation of Horizontally Transferred Genetic Elements

https://doi.org/10.1016/j.cels.2016.06.009Get rights and content
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Highlights

  • An alternative genetic code obstructs propagation of viruses and conjugative plasmids

  • Recoding viruses and plasmids to match the altered genetic code restores propagation

  • Recoded organisms reduce viral population fitness within microbial communities

  • Viruses adapt to match the alternative genetic code and infect recoded organisms

Summary

Horizontally transferred genetic elements such as viruses and conjugative plasmids move DNA between organisms, increasing genetic diversity but destabilizing engineered biological systems. Here, we used a genomically recoded Escherichia coli strain lacking UAG stop codons and the recognition protein release factor 1 to study how an alternative genetic code influences horizontally transferred genetic element propagation. The alternative genetic code conferred resistance to multiple viruses (λ, M13, P1, MS2) at titers up to 1011 PFU/ml and impaired conjugative plasmids (F and RK2) up to 105-fold. By recoding UAG codons to UAA in viruses and plasmids, we restored viral infectivity and conjugative function. Propagating viruses on a mixed community of cells with standard and alternative genetic codes reduced viral titer, and over time viruses adapted to the alternative genetic code. This work demonstrates that altering the genetic code broadly obstructs the propagation of horizontally transferred genetic elements and supports the use of genomic recoding as a strategy to stabilize engineered biological systems.

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