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1. Evolution of a minimal cell

   https://doi.org/10.1038/s41586-023-06288-x  

   Moger-Reischer, R. Z.; Glass, J. I.; Wise, K. S.; Sun, L.; Bittencourt, D. M.; Lehmkuhl, B. K.; Schoolmaster, D. R.; Lynch, M.; Lennon, J. T. (August 2023, Nature)

   Abstract Possessing only essential genes, a minimal cell can reveal mechanisms and processes that are critical for the persistence and stability of life^1,2. Here we report on how an engineered minimal cell^3,4contends with the forces of evolution compared with theMycoplasma mycoidesnon-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 inftsZ, which encodes a tubulin-homologue protein that regulates cell division and morphology^5,6. 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 cells^2,7–9. 

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2. Evolution of a minimal cell

   https://doi.org/10.1101/2021.06.30.450565  

   Moger-Reischer RZ, Glass JI (January 2021, bioRxiv)

   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. 

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3. Essential metabolism for a minimal cell

   https://doi.org/10.7554/eLife.36842  

   Breuer, Marian; Earnest, Tyler M; Merryman, Chuck; Wise, Kim S; Sun, Lijie; Lynott, Michaela R; Hutchison, Clyde A; Smith, Hamilton O; Lapek, John D; Gonzalez, David J; et al (January 2019, eLife)

   One way that researchers can test whether they understand a biological system is to see if they can accurately recreate it as a computer model. The more they learn about living things, the more the researchers can improve their models and the closer the models become to simulating the original. In this approach, it is best to start by trying to model a simple system. Biologists have previously succeeded in creating ‘minimal bacterial cells’. These synthetic cells contain fewer genes than almost all other living things and they are believed to be among the simplest possible forms of life that can grow on their own. The minimal cells can produce all the chemicals that they need to survive – in other words, they have a metabolism. Accurately recreating one of these cells in a computer is a key first step towards simulating a complete living system. Breuer et al. have developed a computer model to simulate the network of the biochemical reactions going on inside a minimal cell with just 493 genes. By altering the parameters of their model and comparing the results to experimental data, Breuer et al. explored the accuracy of their model. Overall, the model reproduces experimental results, but it is not yet perfect. The differences between the model and the experiments suggest new questions and tests that could advance our understanding of biology. In particular, Breuer et al. identified 30 genes that are essential for life in these cells but that currently have no known purpose. Continuing to develop and expand models like these to reproduce more complex living systems provides a tool to test current knowledge of biology. These models may become so advanced that they could predict how living things will respond to changing situations. This would allow scientists to test ideas sooner and make much faster progress in understanding life on Earth. Ultimately, these models could one day help to accelerate medical and industrial processes to save lives and enhance productivity. 

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4. Genetic requirements for cell division in a genomically minimal cell

   https://doi.org/10.1016/j.cell.2021.03.008  

   Pelletier, James F.; Sun, Lijie; Wise, Kim S.; Assad-Garcia, Nacyra; Karas, Bogumil J.; Deerinck, Thomas J.; Ellisman, Mark H.; Mershin, Andreas; Gershenfeld, Neil; Chuang, Ray-Yuan; et al (April 2021, Cell)

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5. Publisher Correction: Evolution of a minimal cell

   https://doi.org/10.1038/s41586-023-06454-1  

   Moger-Reischer, R. Z.; Glass, J. I.; Wise, K. S.; Sun, L.; Bittencourt, D. M.; Lehmkuhl, B. K.; Schoolmaster, D. R.; Lynch, M.; Lennon, J. T. (August 2023, Nature)