RT Journal Article SR Electronic T1 Evolution of a minimal cell JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.06.30.450565 DO 10.1101/2021.06.30.450565 A1 RZ Moger-Reischer A1 JI Glass A1 KS Wise A1 L Sun A1 D Bittencourt A1 M Lynch A1 JT Lennon YR 2021 UL http://biorxiv.org/content/early/2021/08/05/2021.06.30.450565.abstract AB Possessing only essential genes, a minimal cell can reveal mechanisms and processes that are critical for the persistence and stability of life. Here, we report on how a synthetically constructed minimal cell contends with the forces of evolution compared to a non-minimized cell from which it was derived. Genome streamlining was costly, but 80% of fitness was regained in 2000 generations. Although selection acted upon divergent sets of mutations, the rates of adaptation in the minimal and non-minimal cell were equivalent. The only apparent constraint of minimization involved epistatic interactions that inhibited the evolution of cell size. Together, our findings demonstrate the power of natural selection to rapidly optimize fitness in the simplest autonomous organism, with implications for the evolution of cellular complexity.Competing Interest StatementThe authors have declared no competing interest.