Genetic requirements for cell division in a genomically minimal cell

Pelletier, James F.; Sun, Lijie; Wise, Kim S.; Assad-García, Nacyra; Karas, Bogumil J.; Deerinck, Thomas J.; Ellisman, Mark H.; Mershin, Andreas; Gershenfeld, Neil; Chuang, Ronald Y.; Glass, John I.; Strychalski, Elizabeth A.

doi:10.1016/j.cell.2021.03.008

Cited by 90 publications

(102 citation statements)

References 61 publications

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“…While cell size is a complex multigenic trait, previous studies have implicated ftsZ with changes in morphology of the minimal cell (Pelletier et al 2021). It encodes for FtsZ, a protein that localizes to the midcell and determines the site of membrane constriction during cell division.…”

Section: Resultsmentioning

confidence: 99%

“…Prevalent among diverse lineages of bacteria and archaea (McQuillen and Xiao 2020; Liao et al 2021), ftsZ is nevertheless nonessential in M. mycoides . However, cells lacking ftsZ exhibit aberrant cell division and morphology (Hutchison et al 2016; Breuer et al 2019; Pelletier et al 2021). Thus, along with 18 other nonessential genes, ftsZ was retained in JCVI-syn3B to aid in culture maintenance and stable growth (Breuer et al 2019; Pelletier et al 2021).…”

Section: Resultsmentioning

confidence: 99%

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Evolution of a minimal cell

Lennon

Moger-Reischer

Glass

et al. 2021

Preprint

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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 adaption 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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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Evolution of a minimal cell

Lennon

Moger-Reischer

Glass

et al. 2021

Preprint

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“…Two additional cycles of targeted genomic reduction resulted in JCVI-syn3.0, a cell whose synthetic genome is only 531 kbp but still autonomously replicates (Hutchison et al, 2016). Syn3.0 has a slower growth rate than Syn1.0, with a doubling time of approximately 180 min (Hutchison et al, 2016), and based on optical and scanning electron microscopy (SEM), Syn3.0 exhibits a pleomorphic morphology with significant variations (Hutchison et al, 2016;Pelletier et al, 2021). The organism that is the subject of this study, Syn3A, was created from Syn3.0 through the addition of 19 genes present in Syn1.0.…”

Section: Introductionmentioning

confidence: 99%

Generating Chromosome Geometries in a Minimal Cell From Cryo-Electron Tomograms and Chromosome Conformation Capture Maps

Gilbert

Thornburg

Lam

et al. 2021

Front. Mol. Biosci.

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JCVI-syn3A is a genetically minimal bacterial cell, consisting of 493 genes and only a single 543 kbp circular chromosome. Syn3A’s genome and physical size are approximately one-tenth those of the model bacterial organism Escherichia coli’s, and the corresponding reduction in complexity and scale provides a unique opportunity for whole-cell modeling. Previous work established genome-scale gene essentiality and proteomics data along with its essential metabolic network and a kinetic model of genetic information processing. In addition to that information, whole-cell, spatially-resolved kinetic models require cellular architecture, including spatial distributions of ribosomes and the circular chromosome’s configuration. We reconstruct cellular architectures of Syn3A cells at the single-cell level directly from cryo-electron tomograms, including the ribosome distributions. We present a method of generating self-avoiding circular chromosome configurations in a lattice model with a resolution of 11.8 bp per monomer on a 4 nm cubic lattice. Realizations of the chromosome configurations are constrained by the ribosomes and geometry reconstructed from the tomograms and include DNA loops suggested by experimental chromosome conformation capture (3C) maps. Using ensembles of simulated chromosome configurations we predict chromosome contact maps for Syn3A cells at resolutions of 250 bp and greater and compare them to the experimental maps. Additionally, the spatial distributions of ribosomes and the DNA-crowding resulting from the individual chromosome configurations can be used to identify macromolecular structures formed from ribosomes and DNA, such as polysomes and expressomes.

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“…The rational design of minimal genomes using the Mycoplasma genitalium whole-cell model reported minimal genes sets considerably lower than the 473 genes contained in JCVI-syn3.0 (360 and 380) (Rees-Garbutt et al, 2020). While removing individual genes from JCVI-syn3.0 is still possible, combining multiple gene deletions often resulted in greatly reduced growth rates (Breuer et al, 2019;Pelletier et al, 2021). Hence, predictions containing fewer genes than this organism are not likely to be viable.…”

Section: Discussionmentioning

confidence: 99%

Genome‐scale metabolic modeling reveals key features of a minimal gene set

Lachance

Matteau

Brodeur

et al. 2021

Molecular Systems Biology

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Mesoplasma florum, a fast-growing near-minimal organism, is a compelling model to explore rational genome designs. Using sequence and structural homology, the set of metabolic functions its genome encodes was identified, allowing the reconstruction of a metabolic network representing~30% of its protein-coding genes. Growth medium simplification enabled substrate uptake and product secretion rate quantification which, along with experimental biomass composition, were integrated as species-specific constraints to produce the functional iJL208 genome-scale model (GEM) of metabolism. Genome-wide expression and essentiality datasets as well as growth data on various carbohydrates were used to validate and refine iJL208. Discrepancies between model predictions and observations were mechanistically explained using protein structures and network analysis. iJL208 was also used to propose an in silico reduced genome. Comparing this prediction to the minimal cell JCVI-syn3.0 and its parent JCVI-syn1.0 revealed key features of a minimal gene set. iJL208 is a stepping-stone toward model-driven whole-genome engineering.

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Genetic requirements for cell division in a genomically minimal cell

Cited by 90 publications

References 61 publications

Evolution of a minimal cell

Evolution of a minimal cell

Generating Chromosome Geometries in a Minimal Cell From Cryo-Electron Tomograms and Chromosome Conformation Capture Maps

Genome‐scale metabolic modeling reveals key features of a minimal gene set

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