Minimal genome

A minimal genome is the smallest collection of genes able to sustain a self-replicating cell. The idea asks which functions are truly essential for life, such as copying DNA, making RNA and proteins, building membranes and running core metabolism. The answer depends on conditions: a cell bathed in a rich medium that supplies many nutrients needs fewer genes than one that must make everything itself.

Scientists have approached the question in several ways. Comparing genomes of distant bacteria finds genes they all share, and transposon mutagenesis disrupts genes one at a time to see which a cell can lose. Mycoplasmas, bacteria without cell walls that have naturally tiny genomes, are the main models; Mycoplasma genitalium, with about 525 genes, has the smallest known genome of any naturally occurring cell that can replicate on its own. A complication is that two genes may back each other up, so each looks dispensable alone even though the cell cannot lose both.

In 2016 researchers at the J. Craig Venter Institute designed, chemically synthesized and installed a cut-down Mycoplasma mycoides genome with 473 genes, creating the cell JCVI-syn3.0. Even in this stripped-down organism, nearly a third of the genes could not be given a specific function. A slightly larger and more robust version, JCVI-syn3A, is now used to build whole-cell computer models.