Gene circuit-driven amplified selection enables evolution of fast-growing Escherichia coli

Authors

Hamrick, G. S., Son, H.-I., Maddamsetti, R., Zhou, Z., Lok, K., Chen, X., Yip, A., Qian, J.-M., Villalobos, C., Ma, Q., Moghimianavval, H., Shyti, I., Shende, A. R., Chory, E. J., Dunlop, M., You, L.

Abstract

The laboratory Escherichia coli K-12 strain has doubled no faster than ~20 minutes for decades. This plateau could reflect a biophysical limit or simply the way batch culture selects on growth rate. Here we show it can be broken through amplified selection with a Red Queen gene circuit, which takes advantage of growth rate heterogeneity in monoclonal populations to selectively suppress slow-growing cells and creates a tunable mapping from intrinsic growth rate to survival. After 70 days (~1,000 generations) of amplified selection in MG1655+FHr and subsequent removal of the circuit, a top evolved clone (RQ70) reached a maximum specific growth rate of 2.61 h-1 in shake-flask culture. This corresponds to a doubling time of 15.9 minutes, to our knowledge the shortest reported for E. coli K-12, against 18.1 minutes for evolved controls and 20.3 minutes for the ancestor. The gain came at the cost of a ~3-fold increase in lag time, indicating that the 20-minute plateau is a multi-trait optimum under conventional batch selection rather than an absolute constraint. We argue that synthetic gene circuits can therefore reshape the evolutionary process itself, pushing performance beyond apparent physiological limits.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 07 Aug 2026.

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