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Testing Theoretical Minimal Genomes Using Whole-Cell Models.

Joshua Rees-Garbutt^1,2, Jake Rightmyer², Oliver Chalkley^1,3,4

¹BrisSynBio, University of Bristol, Bristol BS8 1TQ, U.K.

ACS Synthetic Biology

|June 10, 2021

Summary

This summary is machine-generated.

Researchers simulated minimal gene sets for life using a Mycoplasma genitalium whole-cell model. They found minimal genomes failed to divide, highlighting the need for species-specific essential genes in synthetic biology.

Keywords:

M. genitalium gene essentiality genome design in silico minimal gene sets whole-cell models

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Area of Science:

Synthetic Biology
Microbiology
Genomics

Background:

Defining the minimal gene set for life is a long-standing theoretical challenge.
Previous minimal genome theories for Mycoplasma genitalium (M. genitalium) could not be experimentally validated due to laboratory limitations.
The development of a M. genitalium whole-cell model offers a novel in silico approach to test these theories.

Purpose of the Study:

To computationally test theoretical minimal gene sets for M. genitalium.
To identify essential and non-essential genes required for cellular division.
To assess the limitations of current gene essentiality data in genome design.

Main Methods:

Simulated existing minimal gene sets in silico using the M. genitalium whole-cell model.
Analyzed the division capability of simulated cells with theoretical minimal genomes.
Reintroduced specific essential and low-essential genes in silico based on prior research to restore cellular division.

Main Results:

In silico simulations of theoretical minimal gene sets resulted in non-dividing cells.
The reintroduction of specific essential and low-essential genes enabled cellular division in the simulated M. genitalium.
The study underscores the critical role of species-specific low-essential genes and their interactions.

Conclusions:

Theoretical minimal gene sets are insufficient for producing viable, dividing cells.
Accurate genome design requires comprehensive understanding and inclusion of species-specific essential and low-essential genes.
Future synthetic genome designs will likely necessitate in vivo validation and gene reintroduction.