Evolution of a minimal cell

Abstract

Possessing only essential genes, a minimal cell can reveal mechanisms and processes that are critical for the persistence and stability of life1,2. Here we report on how an engineered minimal cell3,4 contends with the forces of evolution compared with the Mycoplasma mycoides non-minimal cell from which it was synthetically derived. Mutation rates were the highest among all reported bacteria, but were not affected by genome minimization. Genome streamlining was costly, leading to a decrease in fitness of greater than 50%, but this deficit was regained during 2,000 generations of evolution. Despite selection acting on distinct genetic targets, increases in the maximum growth rate of the synthetic cells were comparable. Moreover, when performance was assessed by relative fitness, the minimal cell evolved 39% faster than the non-minimal cell. The only apparent constraint involved the evolution of cell size. The size of the non-minimal cell increased by 80%, whereas the minimal cell remained the same. This pattern reflected epistatic effects of mutations in ftsZ, which encodes a tubulin-homologue protein that regulates cell division and morphology5,6. Our findings demonstrate that natural selection can rapidly increase the fitness of one of the simplest autonomously growing organisms. Understanding how species with small genomes overcome evolutionary challenges provides critical insights into the persistence of host-associated endosymbionts, the stability of streamlined chassis for biotechnology and the targeted refinement of synthetically engineered cells2,7–9.

Minimal Bacterial Cell JCVI-syn3B as a Chassis to Investigate Interactions between Bacteria and Mammalian Cells

“…Many Gram-positive bacterial lipoproteins are substrate-binding proteins of ABC transporter systems responsible for the acquisition of multiple nutrients including amino acids and short peptides, sugars, polyamines, and many metal ions . It is also known that acquisition and metabolism of carbohydrates are essential for host colonization and pathogenesis of bacterial pathogens. , Since the MMSYN1-0180–0186 genes are present in the same operon ( MMSYN1-0179 is transcribed by itself , ), they might function together contributing with the Mmc cell adherence to the cell host. Interestingly, a predicted maltose ABC transporter malF was found to be necessary for the persistence of Mycoplasma gallisepticum in infected birds .…”

Building Synthetic Cells─From the Technology Infrastructure to Cellular Entities

“…For example, in the case of the JCVI minimal bacterial cell, it was hypothesized that a bacterium whose genome only encoded genes essential for cell-viability might be unable to evolve, mainly because of the absence of DNA-repair mechanisms that would lead to the rapid accumulation of fatal mutations. This idea was disproved recently in adaptive laboratory evolution experiments, demonstrating increased fitness of JCVIsyn3A and JCVI-syn3B after thousands of generations in laboratory culture. , …”

Sandwalking

“…This cell is an engineered, stripped-down version of a bacterium. Nevertheless, researchers documented an increase in fitness over time (Moger-Reischer et al 2023).…”