Minimal Cells—Real and Imagined

Glass, John I.; Merryman, Chuck; Wise, Kim S.; Hutchison, Clyde A.; Smith, Hamilton O.

doi:10.1101/cshperspect.a023861

Cited by 77 publications

(94 citation statements)

References 38 publications

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“…Single‐celled organisms like the marine green alga Ostreococcus tauri or bacteria could be chosen as model systems to discover the simplest cell codes. Simpler still are organisms that result from efforts to generate cells that have a minimal genome . While the analysis of these organisms would reveal the logic of cell codes for single‐celled organisms, it is conceivable that the need for differentiation in complex animals and plants results in fundamentally different strategies for the assembly and reproduction of their cell codes.…”

Section: Approaches To Decipher the Cell Codementioning

confidence: 99%

“…[36] Determining the minimal representation of the cell code of an organism requires minimization of features in a zygote akin to current efforts to minimize the genomes of cells. [37,38] For example, imagine a gene that has two copies of partially transcribed RNA, 32 copies of the spliced RNA, 17 copies of translated protein, 12 copies of the protein with correct subcellular localization, etc., that are all reproduced in the zygote of every generation, i.e., that are all part of the cell code. Which of these details are necessary for the perpetuation of a similar arrangement?…”

Section: What Is the Minimal Information Necessary To Make And Perpetmentioning

confidence: 99%

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Replicating and Cycling Stores of Information Perpetuate Life

Jose

2018

BioEssays

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Life is perpetuated through a single-cell bottleneck between generations in many organisms. Here, I highlight that this cell holds information in two distinct stores: in the linear DNA sequence that is replicated during cell divisions, and in the three-dimensional arrangement of molecules that can change during development but is recreated at the start of each generation. These two interdependent stores of information - one replicating with each cell division and the other cycling with a period of one generation - coevolve while perpetuating an organism. Unlike the genome sequence, the arrangement of molecules, including DNA, RNAs, proteins, sugars, lipids, etc., is not well understood. Because this arrangement and the genome sequence are transmitted together from one generation to the next, analysis of both is necessary to understand evolution and origins of inherited diseases. Recent developments suggest that tools are in place to examine how all the information to build an organism is encoded within a single cell, and how this cell code is reproduced in every generation. See also the video abstract here: https://youtu.be/IdWEL-T6TPU.

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Section: Approaches To Decipher the Cell Codementioning

confidence: 99%

Section: What Is the Minimal Information Necessary To Make And Perpetmentioning

confidence: 99%

Replicating and Cycling Stores of Information Perpetuate Life

Jose

2018

BioEssays

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“…The main approaches to genome simplification fall into two categories: a bottom-up approach in which DNA pieces are assembled into a minimal genome that is tested to see if it can successfully 'boot up' self-replication in a host cell and a top-down approach in which chromosomal regions found to be dispensable are removed in a step-wise fashion to create a streamlined genome. These efforts have led to more efficient and reliable microbial cell factories and blurred the line between chemical and living systems (5)(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Rapid and assured genetic engineering methods applied to Acinetobacter baylyi ADP1 genome streamlining

Suárez

Dugan

Renda

et al. 2019

Preprint

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One goal of synthetic biology is to improve the efficiency and predictability of living cells by removing extraneous genes from their genomes. We demonstrate improved methods for engineering the genome of the metabolically versatile and naturally transformable bacterium Acinetobacter baylyi ADP1 and apply them to a genome streamlining project. In Golden Transformation, linear DNA fragments constructed by Golden Gate Assembly are directly added to cells to create targeted deletions, edits, or additions to the chromosome. We tested the dispensability of 55 regions of the ADP1 chromosome using Golden Transformation. The 19 successful multiple-gene deletions ranged in size from 21 to 183 kilobases and collectively accounted for 24.6% of its genome. Deletion success could only be partially predicted on the basis of a single-gene knockout strain collection and a new Tn-Seq experiment. We further show that ADP1's native CRISPR/Cas locus is active and can be retargeted using Golden Transformation. We reprogrammed it to create a CRISPR-Lock, which validates that a gene has been successfully removed from the chromosome and prevents it from being reacquired. These methods can be used together to implement combinatorial routes to further genome streamlining and for more rapid and assured metabolic engineering of this versatile chassis organism.

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“…Additionally, gene products can perform together as a complex, with individually non-essential genes involved in producing an essential function 14 ; when enough deletions accumulate to disrupt the group, the remaining genes become essential. The cellular death that occurs when redundant essential genes are removed together, or complexes are disrupted, is referred to as synthetic lethality 2,15,16 . A recent review 1 updates gene essentiality from a binary categorisation to a gradient with four categories: no essentiality (if dispensable in all contexts), low essentiality (if dispensable in some contexts, i.e.…”

Section: Introductionmentioning

confidence: 99%

Designing Minimal Genomes Using Whole-Cell Models

Rees

Chalkley

Landon

et al. 2018

Preprint

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In the future, entire genomes tailored to specific functions and environments could be designed using computational tools. However, computational tools to design cells are scarce. Here we present work implementing computational design-simulate-test cycles for genome optimisation based on whole cell modelling. Similar approaches could be adapted to any goal in genome design, but to demonstrate feasibility, we selected the identification of minimal genomes as a proof of concept, using the first (and currently only published) whole cell model, which is for the bacterium Mycoplasma genitalium . Minimal genomes are an ideal goal to test our ideas because there is a very simple functional assay -the cell can either replicate or not. Our computational design-simulate-test cycles produced novel in-silico minimal genomes smaller than JCVI-Syn3.0 , the smallest genome ever synthesised in the lab, and identified 11 redundant essential genes. This work brings computational genome design a step closer.

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Minimal Cells—Real and Imagined

Cited by 77 publications

References 38 publications

Replicating and Cycling Stores of Information Perpetuate Life

Replicating and Cycling Stores of Information Perpetuate Life

Rapid and assured genetic engineering methods applied to Acinetobacter baylyi ADP1 genome streamlining

Designing Minimal Genomes Using Whole-Cell Models

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