The three-domain system is a biological classification introduced by Carl Woese et al. in 1990 that divides cellular life forms into archaea, bacteria, and eukaryote domains. In particular, it emphasizes the separation of prokaryotes into two groups, originally called Eubacteria (now Bacteria) and Archaebacteria (now Archaea). Woese argued that, on the basis of differences in 16S rRNA genes, these two groups and the eukaryotes each arose separately from an ancestor with poorly developed genetic machinery, often called a progenote. To reflect these primary lines of descent, he treated each as a domain, divided into several different kingdoms. Woese initially used the term "kingdom" to refer to the three primary phylogenic groupings, and this nomenclature was widely used until the term "domain" was adopted in 1990.
Parts of the three-domain theory have been fiercly challenged by scientists such as Radhey S. Gupta, who argues that the primary division within prokaryotes should be between those surrounded by a single membrane, and those with two membranes.
The three-domain system adds a level of classification (the domains) "above" the kingdoms present in the previously used five- or six-kingdom systems. This classification system recognizes the fundamental divide between the two prokaryotic groups, insofar as Archaea appear to be more closely related to Eukaryotes than they are to other prokaryotes – bacteria-like organisms with no cell nucleus. The current system sorts the previously known kingdoms into these three domains: Archaea, Bacteria, and Eukarya.
The Archaea are prokaryotic, with no nuclear membrane, distinct biochemistry, and RNA markers from bacteria. The Archaeans possess unique, ancient evolutionary history for which they are considered some of the oldest species of organisms on Earth, most notably their diverse, exotic metabolisms, which allow them to feed on inorganic matter. Originally classified as exotic bacteria, and then reclassified as archaebacteria, the only easy way to distinguish them on sight from "true" bacteria is by the extreme, harsh environments in which they notoriously thrive.
Some examples of archaeal organisms are:
- methanogens – which produce the gas methane
- halophiles – which live in very salty water
- thermoacidophiles – which thrive in acidic high-temperature water
The Bacteria are also prokaryotic; their domain consists of cells with bacterial rRNA, no nuclear membrane, and whose membranes possess primarily diacyl glycerol diester lipids. Traditionally classified as bacteria, many thrive in the same environments favored by humans, and were the first prokaryotes discovered; they were briefly called the Eubacteria or "true" bacteria when the Archaea were first recognized as a distinct clade.
Most known pathogenic prokaryotic organisms belong to bacteria (see  for exceptions). For that reason, and because the Archaea are typically difficult to grow in laboratories, Bacteria are currently studied more extensively than Archaea.
Some examples of bacteria include:
- Cyanobacteria – photosynthesizing bacteria that are related to the chloroplasts of eukaryotic plants and algae
- Spirochaetes – Gram-negative bacteria that include those causing syphilis and Lyme disease
- Actinobacteria – Gram-positive bacteria including Bifidobacterium animalis which is present in the human large intestine
Eukarya are uniquely organisms whose cells contain a membrane-bound nucleus (eukaryotes, eukaryotic). They include many large single-celled organisms and all known non-microscopic organisms. A partial list of eukaryotic organisms includes:
- Kingdom Fungi or fungi
- Kingdom Plantae or plants
- Kingdom Animalia or animals
Each of the three cell types tends to fit into recurring specialities or roles. Bacteria tend to be the most prolific reproducers, at least in moderate environments. Archaeans tend to adapt quickly to extreme environments, such as high temperatures, high acids, high sulfur, etc. This includes adapting to use a wide variety of food sources. Eukaryotes are the most flexible with regard to forming cooperative colonies, such as in multi-cellular organisms, including humans. In fact, the structure of a Eukaryote is likely to have derived from a joining of different cell types, forming organelles.
Parakaryon myojinensis (incertae sedis) is a single-celled organism known by a unique example. "This organism appears to be a life form distinct from prokaryotes and eukaryotes", with features of both.
Parts of the three-domain theory have been challenged by scientists including Ernst Mayr, Thomas Cavalier-Smith, and Radhey S. Gupta. In particular, Gupta argues that the primary division within prokaryotes should be among those surrounded by a single membrane (monoderm), including gram-positive bacteria and archaebacteria, and those with an inner and outer cell membrane (diderm), including gram-negative bacteria. He claims that sequences of features and phylogenies from some highly conserved proteins are inconsistent with the three-domain theory, and that it should be abandoned despite its widespread acceptance.
Recent work has proposed that Eukarya may have actually branched off from the domain Archaea. According to Spang et al. Lokiarchaeota forms a monophyletic group with eukaryotes in phylogenomic analyses. The associated genomes also encode an expanded repertoire of eukaryotic signature proteins that are suggestive of sophisticated membrane remodelling capabilities. This work suggests a two-domain system as opposed to the near universally adopted three-domain system.
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- Gupta, Radhey S. (1998). "Life's Third Domain (Archaea): An Established Fact or an Endangered Paradigm?: A New Proposal for Classification of Organisms Based on Protein Sequences and Cell Structure". Theoretical Population Biology. 54 (2): 91–104. doi:10.1006/tpbi.1998.1376. PMID 9733652.
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- Cavalier-Smith, Thomas (2002). "The neomuran origin of archaebacteria, the negibacterial root of the universal tree and bacterial megaclassification". Int J Syst Evol Microbiol. 52 (1): 7–76. doi:10.1099/00207713-52-1-7. PMID 11837318.
- Spang, Anja (2015). "Complex archaea that bridge the gap between prokaryotes and eukaryotes". Nature. 521: 173–179. Bibcode:2015Natur.521..173S. doi:10.1038/nature14447. PMC 4444528. PMID 25945739.