Viral eukaryogenesis is thehypothesis that thecell nucleus ofeukaryotic life formsevolved from a largeDNA virus in a form ofendosymbiosis within anarchaeon or abacterium. The virus later evolved into the eukaryotic nucleus by acquiringgenes from thehostgenome and eventually usurping its role. The hypothesis was first proposed by Philip Bell in 2001[1] and was further popularized with the discovery of large, complex DNA viruses (such asMimivirus) that are capable ofprotein biosynthesis.
Viral eukaryogenesis has been controversial for several reasons. For one, it is sometimes argued that the posited evidence for the viral origins of thenucleus can be conversely used to suggest the nuclear origins of some viruses.[2] Secondly, this hypothesis has further inflamed the longstanding debate over whether viruses arelivingorganisms.[2]
The viral eukaryogenesis hypothesis posits that eukaryotes are composed of three ancestral elements: a viral component that became the modern nucleus; a prokaryotic cell (anarchaeon according to theeocyte hypothesis) which donated thecytoplasm andcell membrane of modern cells; and another prokaryotic cell (herebacterium) that, byendocytosis, became the modernmitochondrion orchloroplast.
In 2006, researchers suggested that the transition fromRNA toDNA genomes first occurred in the viral world.[3] A DNA-based virus may have provided storage for an ancient host that had previously used RNA to store its genetic information (such host is called ribocell or ribocyte).[2] Viruses may initially have adopted DNA as a way to resistRNA-degradingenzymes in the host cells. Hence, the contribution from such a new component may have been as significant as the contribution fromchloroplasts ormitochondria. Following this hypothesis, archaea,bacteria, and eukaryotes each obtained their DNA informational system from a different virus.[3] In the original paper, it was also anRNA cell at the origin of eukaryotes, but eventually more complex, featuringRNA processing. Although this is in contrast to nowadays' more probable eocyte hypothesis, viruses seem to have contributed to the origin of all three domains of life ('out of virus hypothesis'). It has also been suggested thattelomerase andtelomeres, key aspects of eukaryoticcell replication, have viral origins. Further, the viral origins of the modern eukaryotic nucleus may have relied on multipleinfections of archaeal cells carrying bacterialmitochondrial precursors withlysogenic viruses.[4]
The viral eukaryogenesis hypothesis depicts a model of eukaryotic evolution in which a virus, similar to a modernpox virus, evolved into a nucleus via gene acquisition from existing bacterial and archaeal species.[5] The lysogenic virus then became the information storage center for the cell, while the cell retained its capacities forgene translation and general function despite the viral genome's entry. Similarly, the bacterial species involved in this eukaryogenesis retained its capacity to produce energy in the form ofATP while also passing much of its genetic information into this new virus-nucleusorganelle. It is hypothesized that the moderncell cycle, wherebymitosis,meiosis, andsex occur in all eukaryotes,evolved because of the balances struck by viruses, which characteristically follow a pattern of tradeoff between infecting as many hosts as possible and killing an individual host through viral proliferation. Hypothetically,viral replication cycles may mirror those ofplasmids and virallysogens. However, this theory is controversial, and additional experimentation involving archaeal viruses is necessary, as they are probably the most evolutionarily similar to modern eukaryotic nuclei.[6][7]
The viral eukaryogenesis hypothesis points to the cell cycle of eukaryotes, particularly sex and meiosis, as evidence.[6] Little is known about the origins of DNA or reproduction in prokaryotic or eukaryotic cells. It is thus possible that viruses were involved in the creation of Earth's first cells.[8] The eukaryotic nucleus contains linear DNA with specialized end sequences, like that of viruses (and in contrast to bacterial genomes, which have a circular topology); it usesmRNA capping, and separatestranscription fromtranslation. Eukaryotic nuclei are also capable of cytoplasmic replication. Some large viruses have their own DNA-directedRNA polymerase.[2] Transfers of "infectious" nuclei have been documented in manyparasiticred algae.[9]
Recent supporting evidence includes the discovery that upon the infection of abacterialcell, the giantbacteriophage201 Φ2-1 (of the genusPhikzvirus) assembles a nucleus-like structure around the region of genome replication and uncouples transcription and translation, and synthesized mRNA is then transported into the cytoplasm where it undergoes translation.[10] The same researchers also found that this same phage encodes a eukaryotic homologue totubulin (PhuZ) that plays the role of positioning the viral factory in the center of the cell during genome replication.[11] ThePhuZ spindle shares several unique properties with eukaryotic spindles: dynamic instability, bipolar filament arrays, and centrally positioning DNA.[7]
Analogous to the phage nucleus is theviroplasm, also known as a "virus factory" and "virus inclusion". Viroplasms areinclusion bodies wrapped in lipid membranes and aggregates of viral proteins, and they serve as sites forviral replication and assembly.[12] The viroplasm may serve to protect the viral genome from host cell defense mechanisms,[13] and it also contains viral polymerases for mRNA transcription and DNA replication and repair, separating these processes from the cytoplasm, much like the cell nucleus. Expression of this structure is prevalent among most members of the phylumnucleocytoviricota, notably the nucleocytoplasmic large DNA viruses (NCLDVs).[14]
Phylogenetic analysis determined that the presence of certain eukaryotic proteins in nucleocytoviricota – particularly, ones responsible for DNA replication and repair, mRNA transcription, and mRNA capping – may have preceded the evolution of thelast eukaryotic common ancestor, suggesting the evolution of these proteins in eukaryotes and nucleocytoviruses may have been a result of horizontal gene transfer between ancient nucleocytoviruses and proto-eukaryotes orAsgard archaea.[14][15] The eukaryoticDNA polymerasePol δ, for example, was found to be phylogenetically nested within the clade of nucleocytovirus,mirusvirus, andherpesvirus DNA polymerases, withmedusavirus polymerases being the closest relative to the Pol δ clade;Pol α andPol ε, on the other hand, are more closely related to archaeal PolB DNA polymerases, with Pol ε being derived from Asgard Pol ε.[14] Similarly, the phylogenetic study suggests that eukaryotic and viral RNA polymerases (RNAPs) are deeply related – withRNAP I andRNAP III being basally branching to this viral/eukaryoticRNAP II clade, and are themselves being derived from or are closely related to archaeal RNA polymerases. The evolution of these proteins may have been rapid, and may have resulted from interactions between these viruses and proto-eukaryotes.
Further, many classes of NCLDVs such asmimiviruses have the apparatus to produce m7G capped mRNA and contain homologues of the eukaryotic cap-binding protein eIF4E. Those supporting viral eukaryogenesis also point to the lack of these features in archaea, and so believe that a sizable gap separates the archaeal groups most related to the eukaryotes and the eukaryotes themselves in terms of the nucleus. In light of these and other discoveries, Bell modified his original thesis to suggest that the viral ancestor of the nucleus was an NCLDV-like archaeal virus rather than a pox-like virus.[7]Another piece of supporting evidence is that them7G capping apparatus (involved in uncoupling of transcription from translation) is present in bothEukarya andMimiviridae but not inLokiarchaeota that are considered the nearest archaeal relatives of Eukarya according to theEocyte hypothesis (also supported by the phylogenetic analysis of the m7Gcapping pathway).[7]
Several precepts in the theory are possible. For instance, a helical virus with abilipidenvelope bears a distinct resemblance to a highly simplifiedcellular nucleus (i.e., a DNA chromosome encapsulated within a lipid membrane). In theory, a large DNA virus could take control of a bacterial or archaeal cell. Instead of replicating and destroying thehost cell, it would remain within the cell, thus overcoming the tradeoff dilemma typically faced by viruses. With the virus in control of the host cell's molecular machinery, it would effectively become a functional nucleus. Through the processes of mitosis andcytokinesis, the virus would thus recruit the entire cell as a symbiont—a new way to survive and proliferate.[16]