Out-of-balance growth enables cost-free synthesis of the flagellum and other proteins in a single bacterium
- 1Department of Molecular and Cellular Biology, Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, United States
- 2Computational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, United States
Abstract
The cost of expressing unnecessary genes on growth has been explained at the population level through balanced growth assumptions. However, due to the high degree of stochasticity in growth and gene regulation, it remains unclear how classical growth laws derived from bulk measurements manifest at the level of individual cells. For example, flagellar gene expression, one of the most energy-intensive processes in Escherichia coli, is typically associated with reduced growth rates in bulk measurements. By contrast, we find at the single-cell level that a strikingly opposite behavior coexists: flagellar gene activity is associated with an increase in growth rate. We show that this apparent contradiction, reminiscent of Simpson’s paradox, results from examining in each cell instantaneous growth and gene expression without indiscriminately aggregating the single-cell data like in bulk measurements. We attribute this unrecognized behavior to out-of-balance growth boosts that temporarily offset the burden of flagellum production, likely driven by a surplus of growth factors inherited across cell division. Furthermore, we show that this non-intuitive relationship between growth and gene expression at the single-cell level is general, as we observe similar effects with synthetic systems driving the expression of fluorescent proteins downstream of constitutive promoters. Finally, we use a computational model to show that the inheritance of parental growth factors can explain the apparent contradiction and constitutes a general mechanism for mitigating the short-term cost of nonessential and biosynthetically demanding genes in the single cell.
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BibTeX
@article{alcala2026outofbalance,
title = {{Out-of-balance growth enables cost-free synthesis of the flagellum and other proteins in a single bacterium}},
author = {Mayra Patricia Garcia Alcala and Josiah C Kratz and Philippe Cluzel},
journal = {eLife},
year = {2026},
month = oct,
doi = {10.7554/elife.110747},
url = {https://elifesciences.org/articles/110747},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Out-of-balance growth enables cost-free synthesis of the flagellum and other proteins in a single bacterium
AU - Mayra Patricia Garcia Alcala
AU - Josiah C Kratz
AU - Philippe Cluzel
PY - 2026
DA - 2026/10/28
JO - eLife
DO - 10.7554/elife.110747
UR - https://elifesciences.org/articles/110747
AB - The cost of expressing unnecessary genes on growth has been explained at the population level through balanced growth assumptions. However, due to the high degree of stochasticity in growth and gene regulation, it remains unclear how classical growth laws derived from bulk measurements manifest at the level of individual cells. For example, flagellar gene expression, one of the most energy-intensive processes in Escherichia coli, is typically associated with reduced growth rates in bulk measurements. By contrast, we find at the single-cell level that a strikingly opposite behavior coexists: flagellar gene activity is associated with an increase in growth rate. We show that this apparent contradiction, reminiscent of Simpson’s paradox, results from examining in each cell instantaneous growth and gene expression without indiscriminately aggregating the single-cell data like in bulk measurements. We attribute this unrecognized behavior to out-of-balance growth boosts that temporarily offset the burden of flagellum production, likely driven by a surplus of growth factors inherited across cell division. Furthermore, we show that this non-intuitive relationship between growth and gene expression at the single-cell level is general, as we observe similar effects with synthetic systems driving the expression of fluorescent proteins downstream of constitutive promoters. Finally, we use a computational model to show that the inheritance of parental growth factors can explain the apparent contradiction and constitutes a general mechanism for mitigating the short-term cost of nonessential and biosynthetically demanding genes in the single cell.
SN - 2050-084X
ER -