Testing theoretical minimal genomes using whole-cell models

Summary

The minimal gene set for life has often been theorised, with at least ten produced for Mycoplasma genitalium (M.genitalium) ^1–10. Due to the difficulty of using M.genitalium in the lab ¹¹, combined with its long replication time of 12 - 15 hours ^12–14, none of these theoretical minimal genomes have been tested, even with modern techniques ¹². The publication of the M.genitalium whole-cell model ⁶ provided the first opportunity to test them, simulating the genome edits in-silico. We simulated eight minimal gene sets from the literature ^1–8, finding that they produced in-silico cells that did not divide. Using knowledge from previous research ¹⁵, we reintroduced specific essential and low essential genes, producing dividing in-silico cells. This reinforces the need to identify species-specific low essential genes and their interactions ^14,16.