How Many Genes Can Make a Cell: The Minimal-Gene-Set Concept

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Abstract
Several theoretical and experimental studies have endeavored to derive the minimal set of genes that are necessary and sufficient to sustain a functioning cell under ideal conditions, that is, in the presence of unlimited amounts of all essential nutrients and in the absence of any adverse factors, including competition. A comparison of the first two completed bacterial genomes, those of the parasites Haemophilus influenzae and Mycoplasma genitalium, produced a version of the minimal gene set consisting of ∼250 genes. Very similar estimates were obtained by analyzing viable gene knockouts in Bacillus subtilis, M. genitalium, and Mycoplasma pneumoniae. With the accumulation and comparison of multiple complete genome sequences, it became clear that only ∼80 genes of the 250 in the original minimal gene set are represented by orthologs in all life forms. For ∼15% of the genes from the minimal gene set, viable knockouts were obtained in M. genitalium; unexpectedly, these included even some of the universal ge...