Measuring the burden of hundreds of BioBricks defines an evolutionary limit on constructability in synthetic biology

Noor Radde, Genevieve A. Mortensen, Diya Bhat, Shireen Shah, Joseph J. Clements, Sean P. Leonard, Matthew J. McGuffie, Dennis M. Mishler and Jeffrey E. Barrick ()
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Noor Radde: The University of Texas at Austin
Genevieve A. Mortensen: The University of Texas at Austin
Diya Bhat: The University of Texas at Austin
Shireen Shah: The University of Texas at Austin
Joseph J. Clements: The University of Texas at Austin
Sean P. Leonard: The University of Texas at Austin
Matthew J. McGuffie: The University of Texas at Austin
Dennis M. Mishler: The University of Texas at Austin
Jeffrey E. Barrick: The University of Texas at Austin

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract Engineered DNA will slow the growth of a host cell if it redirects limiting resources or otherwise interferes with homeostasis. Escape mutants that alleviate this burden can rapidly evolve and take over cell populations, making genetic engineering less reliable and predictable. Synthetic biologists often use genetic parts encoded on plasmids, but their burden is rarely characterized. We measured how 301 BioBrick plasmids affected Escherichia coli growth and found that 59 (19.6%) were burdensome, primarily because they depleted the limited gene expression resources of host cells. Overall, no BioBricks reduced the growth rate of E. coli by >45%, which agreed with a population genetic model that predicts such plasmids should be unclonable. We made this model available online for education ( https://barricklab.org/burden-model ) and added our burden measurements to the iGEM Registry. Our results establish a fundamental limit on what DNA constructs and genetic modifications can be successfully engineered into cells.

Date: 2024
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DOI: 10.1038/s41467-024-50639-9

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