The Minimal Genome Project seeks to create a bacterium with the minimal genome necessary to sustain life.
Which microbe is the simplest organism depends on your definition of a living organism. If viruses, prions, satellites, nanobes, nanobacteria (non-free-living subbacterial organisms) are excluded, the simplest free-living organism known is Mycoplasma genitalium, with a genome of only 580,000 base pairs and 482 protein-coding genes. Mycoplasma genitalium is a tiny parasitic bacterium that lives in the digestive and genital tracts of primates.
By comparison, Carsonella ruddii, an endosymbiotic bacterium that lives in plant lice, has a genome of just 159,662 base pairs, with just 182 genes, the smallest known. However, Carsonella ruddii cannot live on its own and, like a virus, depends on the host to survive. Previously, a thermophile that lives around underwater hot springs, Nanoarchaeum equitans, was considered the simplest organism, with a genome of 490,885 base pairs in length and 400 nanometers.
Mycoplasma genitalium and other “ultramicroscopic” bacteria have diameters around 200-300 nanometers, smaller than some large viruses. 200 nm is almost the limit of a conventional light microscope, so an electron microscope or atomic force microscope is needed to observe these organisms. There may be free-living organisms even smaller than that – so-called nanobacteria or nanobes are around 10 to 20 nanometers in size, although their status as living organisms is controversial. No DNA has been successfully extracted from these objects, which may simply be mineral growths. On the other hand, among them may be the simplest organism in the world.
Viruses, which cannot reproduce independently, are obviously smaller and simpler than bacteria. Some of the smallest RNA viruses, retroviruses such as the Rous sarcoma virus, have genomes 3,500 base pairs in length, around 80 nm in diameter, and have only four genes. The smallest DNA viruses have a smaller size (18-26 nm), but larger genomes, around 5,000 base pairs. Bacteria and viruses with tiny genomes tend to have a high proportion of protein-encoding genes (95-98%), compared to larger genomes such as the human genome, where only 1.5% of the genes encode proteins.
In an interesting twist in the story of the simplest organism, Nobel Prize-winning scientist Craig Venter Hamilton Smith, working at the J. Craig Venter Institute, is trying to create an even simpler organism, the Mycoplasma laboratory, which, if successful, it will also be the first example of synthetic life. Taking a Mycoplasma genitalium as a starting point, the team randomly eliminates genes and observes the resulting organism for signs of life. Venter believes that 100 of the 482 protein-coding genes in Mycoplasma are redundant and seeks to synthesize a new genome from scratch containing just 382 genes and then inject it into an eviscerated Mycoplasma genitalium, which would then reanimate, Frankenstein-style. This is called the Minimal Genome Project. The aim is to use the simplest organism to produce large amounts of hydrogen for renewable fuel.