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The simplest free-living organism is Mycoplasma genitalium, with a genome of 580,000 base pairs and 482 protein-coding genes. Carsonella ruddii has the smallest genome of 159,662 base pairs and 182 genes but cannot live on its own. Nanoarchaeum equitans was previously thought to be the simplest organism. Viruses are smaller and simpler than bacteria. Craig Venter is attempting to create an even simpler organism, Mycoplasma laboratorium, through the Minimal Genome Project.
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 only 182 genes, the smallest known. However, Carsonella ruddii cannot live on its own and, like a virus, depends on the host for survival. Previously, a thermophile that lives around underwater hot springs, Nanoarchaeum equitans, was thought to be the simplest organism, with a genome 490.885 base pairs long and 400 nanometers in size.
Mycoplasma genitalium and other “ultramicroscopic” bacteria have diameters in the ballpark of 200-300 nanometers, smaller than some large viruses. 200 nm is about the limits of a conventional light microscope, so an electron microscope or atomic force microscope is needed to observe these organisms. There may be living organisms even smaller than this: so-called nanobacteria or nanobes are around 10-20 nanometers in size, although their status as living organisms is disputed. No DNA has yet been successfully extracted from these objects, which may simply be mineral outgrowths. 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 Rous sarcoma virus, have genomes 3,500 base pairs long, about 80 nm in diameter, and possess only four genes. Smaller DNA viruses have smaller sizes (18-26 nm) but larger genomes, around 5,000 base pairs. Bacteria and viruses with tiny genomes tend to have a high ratio of protein-coding genes (95-98%), compared to larger genomes such as the human genome, where only 1.5% of protein-coding genes.
In an interesting twist on the story of the simpler organism, Nobel Prize-winning scientist Craig Venter Hamilton Smith, who works at the J. Craig Venter Institute, is attempting to create an even simpler organism, Mycoplasma laboratorium, which, in if successful, it will also be the first example of synthetic life. Taking a Mycoplasma genitalium as a starting point, the team randomly knock out the genes and observe the resulting organism for signs of life. Venter believes 100 of the 482 protein-coding genes in Mycoplasma are redundant, and tries to synthesize a new genome containing only 382 genes from scratch, then inject it into an eviscerated Mycoplasma genitalium, which then reanimates, Frankenstein-style. This is called the Minimal Genome Project. The goal is to use the simplest organism to produce large quantities of hydrogen for renewable fuels.
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