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Title: Genomic Recoding Broadly Obstructs the Propagation of Horizontally Transferred Genetic Elements

Horizontally transferred genetic elements such as viruses and conjugative plasmids move DNA between organisms, increasing genetic diversity but destabilizing engineered biological systems. For this, 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 10 11 PFU/ml and impaired conjugative plasmids (F and RK2) up to 10 5-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.
Authors:
 [1] ;  [1]
  1. Yale Univ., New Haven, CT (United States). Systems Biology Inst. and Dept. of Molecular, Cellular and Developmental Biology
Publication Date:
Grant/Contract Number:
FG02-02ER63445; T32GM007499; T32GM007223; HR0011-15-C-0091; 1R01GM117230-01
Type:
Published Article
Journal Name:
Cell Systems
Additional Journal Information:
Journal Volume: 3; Journal Issue: 2; Journal ID: ISSN 2405-4712
Research Org:
Harvard Univ., Cambridge, MA (United States)
Sponsoring Org:
USDOE; National Institutes of Health (NIH); Gruber Foundation; Defense Advanced Research Projects Agency (DARPA); Gen9, Cambridge, MA (United States); DuPont, Wilmington, DE (United States); Arnold and Mabel Beckman Foundation
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES
OSTI Identifier:
1394715
Alternate Identifier(s):
OSTI ID: 1466971

Ma, Natalie Jing, and Isaacs, Farren J. Genomic Recoding Broadly Obstructs the Propagation of Horizontally Transferred Genetic Elements. United States: N. p., Web. doi:10.1016/j.cels.2016.06.009.
Ma, Natalie Jing, & Isaacs, Farren J. Genomic Recoding Broadly Obstructs the Propagation of Horizontally Transferred Genetic Elements. United States. doi:10.1016/j.cels.2016.06.009.
Ma, Natalie Jing, and Isaacs, Farren J. 2016. "Genomic Recoding Broadly Obstructs the Propagation of Horizontally Transferred Genetic Elements". United States. doi:10.1016/j.cels.2016.06.009.
@article{osti_1394715,
title = {Genomic Recoding Broadly Obstructs the Propagation of Horizontally Transferred Genetic Elements},
author = {Ma, Natalie Jing and Isaacs, Farren J.},
abstractNote = {Horizontally transferred genetic elements such as viruses and conjugative plasmids move DNA between organisms, increasing genetic diversity but destabilizing engineered biological systems. For this, 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.},
doi = {10.1016/j.cels.2016.06.009},
journal = {Cell Systems},
number = 2,
volume = 3,
place = {United States},
year = {2016},
month = {8}
}