4.8 Article

Genetic requirements for cell division in a genomically minimal cell

Journal

CELL
Volume 184, Issue 9, Pages 2430-+

Publisher

CELL PRESS
DOI: 10.1016/j.cell.2021.03.008

Keywords

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Funding

  1. Fannie and John Hertz Foundation Fellowship
  2. Mitchison lab at Harvard Medical School
  3. Fakhri lab at MIT
  4. National Institute of Standards and Technology
  5. National Science Foundation [MCB 1840320, MCB 1818344]
  6. Synthetic Genomics, Inc.
  7. Defense Advanced Research Projects Agency's Living Foundries program [HR0011-12-C-0063]
  8. J. Craig Venter Institute
  9. NIH from the National Institute of General Medical Sciences [P41GM103412]

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Research has shown that in genomically minimal cells, cell division and morphology are controlled by multiple genes, requiring the action of a series of genes to restore a phenotype similar to that of the original cell.
Genomically minimal cells, such as JCVI-syn3.0, offer a platform to clarify genes underlying core physiological processes. Although this minimal cell includes genes essential for population growth, the physiology of its single cells remained uncharacterized. To investigate striking morphological variation in JCVI-syn3.0 cells, we present an approach to characterize cell propagation and determine genes affecting cell morphology. Microfluidic chemostats allowed observation of intrinsic cell dynamics that result in irregular morphologies. A genome with 19 genes not retained in JCVI-syn3.0 generated JCVI-syn3A, which presents morphology similar to that of JCVI-syn1.0. We further identified seven of these 19 genes, including two known cell division genes, ftsZ and sepF, a hydrolase of unknown substrate, and four genes that encode membrane-associated proteins of unknown function, which are required together to restore a phenotype similar to that of JCVIsyn1.0. This result emphasizes the polygenic nature of cell division and morphology in a genomically minimal cell.

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