Testing Theoretical Minimal Genomes Using Whole-Cell Models

The minimal gene
set for life has often been theorized, with at
least ten produced for Mycoplasma genitalium (M. genitalium). Due to the difficulty of using M. genitalium in the lab, combined with its long replication
time of 12–15 h, none of these theoretical minimal genomes
have been tested, even with modern techniques. The publication of
the M. genitalium whole-cell model provided
the first opportunity to test them, simulating the genome edits in silico. We simulated minimal gene sets from the literature,
finding that they produced in silico cells that did
not divide. Using knowledge from previous research, we reintroduced
specific essential and low essential genes in silico; enabling cellular division. This reinforces the need to identify
species-specific low essential genes and their interactions. Any genome
designs created using the currently incomplete and fragmented gene
essentiality information will very likely require in vivo reintroductions to correct issues and produce dividing cells.