
Researchers discover a new virus called the "ushikuvirus" that provide evidence for the viral eukaryogenesis hypothesis and reveal virus-host interactions, shaping the evolution of eukaryotic cells.
One of the remaining questions in evolutionary biology is how the complex (eukaryotic) cell acquired its defining feature: a membrane-bound nucleus in which the DNA is stored.
Prokaryotic cells — bacteria and archaea — possess a single circular DNA molecule located in the cytoplasm. By contrast, all eukaryotic cells contain their genetic material within a membrane-bound nucleus. Now scientists at the Graduate School of Science, Tokyo University of Science (TUS), Japan, led by Professor Masaharu Takemura, have provided further evidence that the eukaryotic nucleus may have originated from a giant DNA virus, similar to those that infect certain species of amoeba. Their findings suggest that the origin of the nucleus may be closely linked to the evolutionary history of this class of virus as it adapted to different hosts.
Professor Takemura and Dr Philip Bell, from the Department of Biological Sciences at Macquarie University, Sydney, independently proposed the viral eukaryogenesis theory (a term coined by Dr Bell) in 2001, suggesting that large DNA viruses — such as poxviruses — might represent plausible ancestors. Since then, beginning in 2003, the discovery of several giant DNA viruses has provided more compelling candidates. When these viruses infect a host cell, they establish so-called ‘virus factories’ within the cytoplasm. In some cases these structures are enclosed within membranes that resemble the nuclear envelope.
The hypothesis proposes that, rather than destroying its host, such a virus formed a long-term association with it. Over evolutionary time, it may have incorporated host genes and transitioned from parasite to symbiotic genetic compartment — eventually becoming the nucleus.
For advocates of “irreducible complexity”, the nucleus is often presented as an all-or-nothing structure: a fully formed membrane, nuclear pores, transport machinery, chromatin organisation and regulatory systems supposedly appearing together or not at all. Yet the viral eukaryogenesis model shows how this argument collapses once intermediate stages are recognised. Giant DNA viruses already construct membrane-bound replication compartments inside host cells; they encode components involved in DNA replication, transcription and even elements of translation.
These viral “factories” function as semi-autonomous genetic centres within the cytoplasm — in effect, simplified proto-nuclei. If such a structure entered into a stable symbiotic relationship with a host cell, incremental gene exchange and co-evolution could gradually integrate and refine the system. Each step would confer immediate functional advantages — protection of DNA, separation of transcription from translation, improved regulation — without requiring the simultaneous appearance of a fully modern nucleus. What is claimed to be irreducible instead looks like a product of stepwise evolutionary integration.
Now Professor Takemura’s team report the discovery of a new giant DNA virus infecting amoebae — the ushikuvirus, named after Lake Ushiku where it was isolated — lending further support to the viral eukaryogenesis theory. Their discovery is reported in Journal of Virology.
Giant DNA Viruses^ Blurring the Line Between Virus and Cell.What are giant viruses?
Mimivirus infecting Acanthamoeba polyphaga. Transmission electron microscope image that shows A. polyphaga infected with Mimivirus. Note the giant virus factory. N, nucleus; VF, virus factory; MV, Mimivirus virions.Source: ResearchGate
So-called “giant viruses” are members of a group collectively known as the Nucleocytoviricota (formerly grouped as nucleocytoplasmic large DNA viruses, NCLDVs). Unlike typical viruses, which are tiny and genetically minimalist, these viruses:
- Possess very large double-stranded DNA genomes (often >1 million base pairs)
- Encode hundreds — sometimes over a thousand — genes
- Can be physically larger than some bacteria, visible under light microscopy
Famous examples include Mimivirus, Pandoravirus, and Pithovirus.
Why were they so surprising?
When Mimivirus was discovered in 2003 infecting amoebae, it challenged the long-held view that viruses are always small and genetically simple. Some giant viruses encode:
- DNA repair enzymes
- Components involved in transcription
- Translation-related proteins (previously thought exclusive to cells)
- Cytoskeletal-like proteins
- Complex regulatory factors
Although they still depend on a host cell for full replication, their genetic repertoire blurs the once-clear distinction between cellular life and viruses.
Viral “factories”
After infecting amoebae such as Acanthamoeba, many giant viruses construct membrane-bounded replication compartments inside the cytoplasm. These “virus factories”:
- Concentrate viral DNA and replication machinery
- Exclude much of the host cytoplasm
- Resemble simplified nuclei in organisation
This architectural similarity is central to the viral eukaryogenesis hypothesis, which proposes that an ancestral giant virus may have evolved into the modern eukaryotic nucleus through long-term symbiosis.
Evolutionary significance
Giant viruses appear to have evolved through a combination of:
- Gene acquisition from hosts
- Gene duplication and expansion
- Reductive evolution from more complex ancestors (a debated possibility)
Their genomes are mosaics, reflecting extensive horizontal gene transfer. This dynamic genetic exchange makes them plausible evolutionary intermediates in scenarios involving symbiosis and cellular integration.
Why they matter for the nucleus debate
If viruses can already:
- Construct membrane-bound genetic compartments
- Encode transcription machinery
- Exchange genes with hosts
then the conceptual leap from “virus factory” to integrated nuclear compartment becomes far less dramatic than irreducible complexity arguments assume. Rather than appearing fully formed, the nucleus may represent the evolutionary stabilisation of a once-parasitic genetic enclave.
Further details of the research and the biology of these giant viruses are available in a news release from Tokyo University.
Ushikuvirus: A Newly Discovered Giant Virus May Offer Clues to the Origin of Life
Ushikuvirus, an amoeba-infecting giant virus, joins the family of giant viruses that may have driven the evolution of complex cells
The origin of life on Earth becomes even more fascinating and complex as we peer into the mysterious world of viruses. Said to have existed since living cells first appeared, these microscopic entities differ greatly from other forms of life. Composed of only genetic material, they lack the ability to synthesize proteins, which are essential for carrying out cellular activity and, ultimately, for life by itself.
As a result, scientists have long sought to unravel virus origins, how they evolve, and how they fit into the conventional tree of life. Professor Masaharu Takemura from the Graduate School of Science, Tokyo University of Science (TUS), Japan, has been at the forefront of this search. In 2001, he, along with Dr. Philip Bell, from the Department of Biological Sciences, Macquarie University, Sydney, independently proposed the cell nuclear virus origin theory, also known as viral eukaryogenesis (term coined by Dr. Bell). According to this hypothesis, the nucleus of eukaryotic cells (cells whose nucleus is bound by a membrane) originated from a large DNA virus such as poxvirus that infected an archaeal ancestor (single-celled microorganisms). Instead of killing the host, the virus set up a long-term presence inside the cytoplasm, and over time acquired essential genes from the host, and became what we now recognize as the nucleus of eukaryotic cells. This suggests that viruses may have played a foundational role in the emergence of life.
Nowadays, central to this idea are giant viruses that contain DNA, which were found in 2003. When they infect cells, they form specialized structures called virus factories inside the host. Some of these factories are enclosed within a membrane, much like a cell nucleus, where DNA replication takes place, hinting at an evolutionary connection between viruses and complex cells.
In recent years, new types of DNA viruses have been discovered, including members of the family Mamonoviridae, which infect acanthamoeba (a type of amoeba, which is a single-celled microorganism), and the closely related clandestinovirus, which infects vermamoeba (another type of amoeba from a different family).
Now, in a joint study published online in the Journal of Virology on November 24, 2025, Prof. Takemura along with researchers at the National Institute of Natural Sciences (NINS), Japan, report yet another of these giant DNA viruses that infect amoeba. Named ushikuvirus after Lake Ushiku in the Ibaraki Prefecture of Japan, where it was isolated. This discovery offers further support for the nuclear virus origin hypothesis.
The team included Mr. Jiwan Bae and Mrs. Narumi Hantori, Master's degree students at the Graduate School of Science, TUS, along with Dr. Raymond Burton-Smith and Professor Kazuyoshi Murata from NINS.
Giant viruses can be said to be a treasure trove whose world has yet to be fully understood. One of the future possibilities of this research is to provide humanity with a new view that connects the world of living organisms with the world of viruses.
Professor Masaharu Takemura, corresponding author.
Department of Mathematics and Science Education
Graduate School of Science
Tokyo University of Science
Tokyo, Japan.
Giant viruses are ubiquitously present in the environment. However, their isolation remains a challenge. These viruses are highly diverse and the discovery of ushikuvirus is extremely valuable. The newly discovered ushikuvirus infects vermamoeba, like clandestinovirus, and is morphologically similar to members of the Mamonoviridae family, particularly Medusavirus, a genus characterized by its icosahedral shape and numerous short spikes on the capsid surface. However, ushikuvirus also shows distinct features: it induces a specific cytopathic effect that causes its vermamoeba hosts to grow into unusually large cells, and it possesses multiple spike structures with unique caps on the capsid surface, some with filamentous extensions, not seen in medusaviruses.
Additionally, unlike medusaviruses and clandestinovirus, which replicate within the intact host nucleus, ushikuvirus disrupts the nuclear membrane to produce viral particles. This suggests a phylogenetic link between Mamonoviridae family that utilizes intact nucleus as viral factory and giant viruses like pandoravirus that disrupt the nuclear membrane for replication. Researchers believe that these variations between viruses may have evolved as adaptations to their hosts.
By comparing these structural and functional differences, researchers are beginning to piece together how giant viruses have diversified over time and how their interactions with host cells may have shaped the evolution of complex eukaryotic life.
The discovery of a new Mamonoviridae-related virus, 'ushikuvirus,' which has a different host, is expected to increase knowledge and stimulate discussion regarding the evolution and phylogeny of the Mamonoviridae family. As a result, it is believed that we will be able to get closer to the mysteries of the evolution of eukaryotic organisms and the mysteries of giant viruses.
.Professor Masaharu Takemura.
The discovery of these amoeba-infecting viruses could have practical implications for healthcare. Because certain Acanthamoeba species can cause diseases such as amoebic encephalitis, understanding how giant viruses infect and destroy amoebae may one day help scientists develop new strategies to prevent or treat such infections.
Ushikuvirus: a new giant virus infecting amoebae
A joint research team discovered and characterized ushikuvirus, a new giant DNA virus that infects vermamoeba. This image (a) shows the 3D reconstruction of the virus, highlighting its spiked capsid (d). The finding further supports the nuclear virus origin hypothesis, which proposes that viruses played a role in the evolution of eukaryotic cells.Image credit: Professor Kazuyoshi Murata. Source CC BY 4.0
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What this research underlines — yet again — is how far removed real biology is from the caricature so often presented by creationists. No serious biologist imagines that a fully formed eukaryotic cell — complete with nucleus, mitochondria, cytoskeleton and membrane systems — somehow “self-assembled” in a single miraculous leap from inorganic chemicals. That parody bears no resemblance to evolutionary theory. What the evidence increasingly shows instead is a mosaic process: incremental integration, symbiosis, gene exchange, co-option and modification over immense spans of time.
The viral eukaryogenesis hypothesis fits naturally into the broader picture already established for mitochondria. Just as mitochondria are now recognised as the descendants of once free-living bacteria that entered into a stable symbiotic partnership with an ancestral archaeal host, the nucleus itself may represent the stabilised remnant of an ancient giant DNA virus that became domesticated rather than destructive. In both cases, complexity did not appear all at once. It accumulated through evolutionary negotiation between formerly independent biological entities.
The eukaryotic cell, then, is not a monument to sudden creation but a record of ancient alliances — bacteria becoming mitochondria, viruses becoming nuclei, genes shuttling between lineages, cellular systems merging and specialising. What appears today as an integrated, “irreducibly complex” whole is better understood as the long-term outcome of evolutionary tinkering.
Far from supporting a simplistic narrative of spontaneous assembly or supernatural intervention, discoveries like ushikuvirus reinforce a far richer and more fascinating story: complex cells are historical composites, shaped by symbiosis and natural selection over billions of years. No magic required.
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