Giant Viruses Are Degenerate Higher Cells, New Study Suggests

The Mimivirus genome is more like that of eukaryotes than bacteria or archaea, says study from Institute of Technology Bombay

Ruth Schuster
Ruth Schuster
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A three dimensional model of a mimivirus.
A three dimensional model of a mimivirus.Credit: nobeastsofierce / Shutterstock
Ruth Schuster
Ruth Schuster

Viruses were enigmatic enough – are they a living creature? A collection of inert chemicals that can, with help, replicate? An infectious crystal? Nowadays they are pure parasites, but did their evolution necessarily post-date other life forms?

Then giant ones were discovered in 2003, inside amoebas that were themselves inside a water tower in England, and upset the theories. The Mimiviruses, as they came to be called, were so enormous that they were mistaken for bacteria at first.

Among other things the Mimiviruses are parasites that infect unicellular organisms, and their genomes are far more complicated than those of their smaller brethren. Since being identified as non-bacteria, and the realization that they are far more complex than other types of viruses, inquiring minds have wondered what the devil they are and whence they originated.

Now a team of researchers at the Indian Institute of Technology Bombay has published a study in Molecular Biology and Evolution suggesting that the Mimiviruses evolved from eukaryotes, i.e., complex cells with nuclei.

Molecular virologists Dr. Kiran Kondabagil and Dr. Supriya Patil created phylogenetic trees for replication proteins in various life forms, and realized that the Mimivirus’ genes were more closely related to those of eukaryotes than to bacteria or small viruses.

“There are several hypotheses for the origin of the Mimivirus,” Kondabagil explains to Haaretz. Nor is his team the first to suggest the eukaryote origin, he stresses. But he and the team took a new approach, and their results shore up that controversial eukaryote-origin theory, he explains.

Their research also supports the hypothesis that Mimiviruses are very ancient, as opposed to the competing theory that they evolved from bacteriophages (viruses that attack bacteria) relatively recently, the team explains.

An illustration showing the size of giant viruses compared to bacterium and normal viruses.Credit: Meletios Verras / Shutterstock
Dr. Kiran KondabagilCredit: Dr. Kiran Kondabagil

When life was simpler

Life can be broken down into viruses, prokaryotes and eukaryotes, though it bears qualifying that not everyone thinks viruses are a form of life. Viruses by and large consist of genetic material – RNA or DNA, coding for a few genes – wrapped in a protein shell. Prokaryotes include bacteria and archaea (formerly known as archaebacteria); their DNA is not encased in a nucleus, but floats sort of freely inside the cell.

Eukaryotes are all the rest, from amoebas to us folks: The cells have nuclei that contain their DNA, with the exception of their mitochondrial DNA.

The fact that the Mimivirus has double-stranded DNA is neither here nor there: All eukaryotes do but then so do bacteria, albeit in their case, it makes up their one free-floating chromosome. Some viruses do too, including our friend the herpesviridae.

So basically viruses are the simplest form of life, and we shall not dwell here on the argument over whether they are life forms or replicating crystals, nor bog down on prions. Viruses do not have genes that govern their own replication, by and large: They count on the cells they attack to handle that. Outside the cell, they are inert, which is one reason why some insist they are not “alive.” Bacteria and archaea come next in complexity: Many are parasites but they are capable of reproduction.

The most complex are the eukaryotes, nucleated cells, from the amoeba to the palm tree to the elephant. Many unicellular creatures and all multicellular animals are eukaryotic.

Mimiviruses upset our neat little map of life by being viruses that sport very advanced genetic characteristics. Just one surprise they sprang is that they have genes involved in DNA replication, transcription and even translation, if not the full set.

No, the Mimivirus cannot replicate itself, Kondabagil assures; for that it remains completely dependent on the host – but unlike its smaller cousins, it has a lot of the equipment. That in and of itself argues in favor of descent from a higher cell. This hypothesis goes on to suggest that during evolution, the Mimivirus lost other genes coding for vital metabolic processes.

Degeneration or a sort of reverse evolution is not unknown. Take for example myxozoans, which are microscopic parasites consisting of one to a few cells, that – to the profound shock of biologists – turned out to be massively degenerated jellyfish. At least one species is so reductive that it lost its ability to breathe and leeches oxygen from its host. So that capacity, to start high and end low, is out there.

Mimivirus alongside two virophages, seen through an electron microscope.Credit: Sarah Duponchel and Matthias G.

Jumping start

The new study is based on the characteristics of the Mimiviral DNA.

In general, previous work studied specific Mimivirus sequences that code for proteins and that match with known ones elsewhere. Some genes matched with bacteria, some with archaea and some with eukaryotes. So looking at specific sequences containing coding for specific proteins was not terribly helpful, Kondabagil explains.

So he and Supriya looked at all the Mimivirus’ sequences that are involved in replication (when it infects a host) and realized that most were like those in eukaryotes, and were unlike parallel bacteria mechanisms, he says.

What about gene transfers, transposons, jumping genes - mechanisms by which genes pass from one being to another? For instance, resistance to antibiotics may be passed from one bacteria to another, and they don’t have to belong to the same species, by “jumping genes.” Could the ancestral Mimivirus have gained a bunch of eukaryotic genes in a similar fashion?

Theoretically it’s not impossible, but it’s unlikely, he answers. “What we did is look at the entire process of replication,” Kondabagil explains. “A given virus can’t have just borrowed the entire replication mechanism from someplace else.”

Thus they realized that most of the enzymes involved in the replication mechanism of the Mimivirus in question were most similar to eukaryotes, not bacteria or archaea, which had, over time, co-evolved alongside the similar genes in the eukaryotes.

They did actively look for gene transfers and deduced that three of the Mimiviral proteins had been acquired from some other source. But a majority of representative code components were unchanged from the time they sort of deviated from whatever ancestor they arose from, he explains.

Indeed genes for replication are generally conserved, Kondabagil says: This means they tend not to change (mutate) over time because mutations are fatal; thus it is plausible that if a eukaryote origin and Mimivirus descendant began with the same replication genes, and they were necessary for both, they will remain similar even over vast spans of time.

They also detected signals that the proteins co-evolved, which means that they are linked together in a larger protein complex with coordinated function.

A microscopic image of Tupanvirus, a member of the giant virus family.Credit: Jnatas Abraho

Taken together, these results imply that Mimiviral DNA replication machinery is ancient, the team explains – which supports the reduction hypothesis, an origin that began with a complex ancestor.

So is all this proof that the Mimivirus originated as an eukaryote? It is not. Dr. Kondabagil phrases his conclusion with due caution: “We hypothesize that these mimuviruses probably, might, have cellular origin,” he says.

Alternatively, the Mimivirus could have begun as a virus and, after all, gained genes from the others over time.

Billions of years old

At the end of the day, Kondabagil explains, when engaging in bioinformatics, one tries to look for explanations and deduce the minimum number of events for something to emerge – the probability of something happening decreases with the number of events; all individual events are probabilities and highly inferential.

Why would anybody care about the origin of the Mimivirus? Because it’s interesting, but there could be a pragmatic aspect. “Because these single-celled organisms greatly influence the carbon turnover in the ocean, the viruses have an important role in our world’s ecology. So, it is just as important to study them and their evolution as it is to study the disease-causing viruses,” he explains.

So how old is the Mimivirus? Again the jury is out, but his work leads him to suspect that the last cellular ancestor of the beast, if there was one, lived about 3.5 billion years ago. We cannot even say at this point whether the Mimivirus family is monophyletic, arising from a primordial ancestor who likely emerged before prokaryotes and eukaryotes even split; or polyphyletic, originating from multiple ancestral mimiviruses.

Likely, we will never know the precise origin story, but not for lack of trying to deduce it.

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