A computational approach to the functional screening of genomes

Area of Science:

• Computational Biology
• Genomics
• Systems Biology

Background:

• Comparative genomics aims to understand genome function by comparing genes.
• Mushegian and Koonin proposed a Minimal Gene Set (MGS) for the oldest ancestor genome.
• The viability of an organism with MGS remains an open question.

Purpose of the Study:

• To computationally assess the viability of a prokaryote based on the Minimal Gene Set (MGS).
• To determine if the MGS allows for metabolic equilibrium and biomass production.
• To iteratively modify the MGS to achieve a viable virtual organism.

Main Methods:

• In silico metabolic pathway reconstruction of an MGS-based prokaryote.
• Dynamic simulation of cellular metabolic activities.
• Iterative gene set refinement and functional replacement.

Main Results:

• The original MGS failed to support metabolic equilibrium and biomass production, indicating non-viability.
• Removing 76 redundant genes and adding 7 critical enzymes resulted in a 187-gene genome.
• The modified genome yielded a virtual cell (ViCe) exhibiting homeostasis and biomass production.

Conclusions:

• The Minimal Gene Set (MGS) alone is insufficient for cellular life.
• A refined genome, represented by the Virtual Cell (ViCe), demonstrates in silico viability.
• ViCe's metabolic steady-state concentrations resemble experimentally observed bacterial data.