He finally demonstrated that the division of the living world between prokaryotes and eukaryotes was misleading in term of natural classification (Woese and Fox 1977). He showed that a group of organisms previously considered to be bacteria, according to their “prokaryotic phenotype” (they have Belnacasan chemical structure no nucleus) was in fact no more related to bacteria than to eukaryotes in terms of their ribosomes (more precisely their ribosomal RNA). Although all ribosomes (the cellular organelles that synthesize

proteins) are homologous in the living world, there are three versions of them. Woese and Fox concluded that living organisms should therefore be divided into three primary lineages, originally called eubacteria, archaebacteria and eukaryotes (Woese and Fox 1977). Later on, Woese and colleagues proposed to replace this nomenclature by a new one: bacteria, archaea and eukarya, to prevent

further confusion between the two prokaryotic domains (archaea are not “strange” or “old” bacteria”, AG-014699 supplier but a domain with equal taxonomic status compared to bacteria and eukarya) (Woese et al. 1990). This trinity concept has now been corroborated by comparative biochemistry and comparative genomics. Amazingly, although archaea superficially resemble bacteria when they are examined under the microscope, they are much more similar to eukarya when they are analyzed at the molecular level (Forterre et al. 2002, for recent monographies on archaea, see ref. Cavicchioli 2007; Garrett and Klenk 2007). For example, there are 33 ribosomal proteins that are common to archaeal and eukaryotic ribosomes but are absent in bacteria (Lecompte et al. 2002). The discovery of unique viruses infecting archaea also corroborates the three domains concept from the virus perspective. Indeed, most viruses infecting archaea have nothing in common 17-DMAG (Alvespimycin) HCl with those infecting bacteria, although they are still considered as “bacteriophages” by many virologists, just because archaea and bacteria are both prokaryotes (without nucleus). A first

step in a natural classification of viruses was thus to get rid of the dichotomy between bacteriophages and viruses, and to superimpose a viral trichotomy to the cellular trichotomy. David Prangishvili and myself have thus suggested to classify viruses into three categories, archaeoviruses, bacterioviruses and eukaryoviruses (Forterre and Prangishvili 2009). Viruses Are Ancient and Have Played a Major Role in Biological Evolution The last common ancestor of archaea, bacteria and eukarya is today usually called LUCA (the Last Universal Common Ancestor, or the Last Universal Cellular Ancestor). The ubiquitous existence of viruses infecting members of the three cellular domains strongly suggests that the cellular lineage of LUCA and the other cellular lineages living at that time were already victims of viral attacks.