Search for a command to run...
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 E. 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.It is recognized from population-level studies that overproduction of unnecessary proteins slows bacterial growth, especially for the energetically costly flagellum. However, population averages can mask the dynamics of growth and synthesis in individual cells. In this work, we examined protein expression and growth rate in E. coli in single cells and found that transient increases in growth rate accompany flagellar production, contrasting with the expectation that overproduction always reduces growth rate. We found similar results for constitutively expressed fluorescent proteins. A stochastic computational model supports the hypothesis that beneficial growth factors inherited from the mother cell at division boost growth and protein synthesis. These findings reveal that individual bacteria may take advantage of out-of-balance growth processes to temporarily offset costly protein production.