RT Journal Article SR Electronic T1 Testing theoretical minimal genomes using whole-cell models JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.03.26.010363 DO 10.1101/2020.03.26.010363 A1 Joshua Rees-Garbutt A1 Jake Rightmyer A1 Oliver Chalkley A1 Lucia Marucci A1 Claire Grierson YR 2020 UL http://biorxiv.org/content/early/2020/10/02/2020.03.26.010363.abstract AB The minimal gene set for life has often been theorised, 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 hours, 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 eight 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.Competing Interest StatementThe authors have declared no competing interest.