Pandoraviruses: Unique in nature, these giant viruses make genes. They are everywhere but their origin is unknown.

They're big bugs, unusually big for viruses. So huge, it's a wonder they could be under the radar of scientists until... 2013. The first "pandoravirus" was spotted on a beach in Chile. Then things picked up speed and we started finding them all over the place. A French scientific team has just revealed that these viruses have a unique characteristic in nature: they make genes from scratch. This discovery calls into question everything we thought we knew about the evolution of life. But the burning question no one can answer is: where do they come from?
Che pandoravirus is aptly named. Like the Pandora's box of mythology, they are mysterious and their contents are likely to bring great surprises. A team of researchers from the Genomic and Structural Information Laboratory (CNRS/Aix-Marseille University), associated with the Large-Scale Biology Laboratory (CEA/Inserm/University of Grenoble-Alpes) and CEA-Genoscope, led by Chantal and Jean-Michel Claverie, have opened the lid of Pandora's Box. What they found there revolutionizes everything we know about the evolution of living things and opens up an abyss of questions. Their work has just been published in the prestigious journal Nature.

Virus or living organism?

For a long time we wondered if a virus was a living organism. The answer is not clear-cut, but if one assumes that a living organism is capable of fending for itself in life, viruses are not. Indeed, they are not equipped to support themselves. They have a very small gene pool, insufficient to allow them to multiply, unlike any bacterium, living cell or plant. Viruses need to parasitize another cell to hijack the cellular machine for their own benefit. Until they have found a suitable host cell, they can remain in stasis, inactive, for thousands of years.
But this view was overturned with the discovery of the first giant viruses. These mastodons contain thousands of genes, infinitely more than a "normal" virus, and their functioning is as complex if not more complex than that of living cells.
The first family of megaviruses was described in the literature in 2003; it was named Mimiviridae after being confused with a small gram-positive bacterium. Most viral particles are measured on the scale of a handful of nanometers, but not this "mimic bacterium" - it is hundreds of times larger, reaching just under a micrometer.

Discovery of monsters

In tracking other examples of Mimivirus in the amoebic cells where they live, researchers stumbled upon a second monster of similarly impressive size.
The details of two new pandoravirus species have been published in 2013. One of them was found in the sediment of Tunquen Beach in Chile. The other was isolated from amoeba breeding in a pond next to Latrobe University in Australia. A third was retrospectively identified two years later in a study cases of amoeba contaminating the contact lens case of a woman diagnosed with keratitis in 2008.
The discovery of the two giant viruses of 2013 looking like nothing known blurred the line between the viral and cellular worlds. These pandoraviruses are as large as bacteria and have genomes more complex than those of some eukaryotic organisms. But their strangeness - a novel form of amphora, a huge and atypical genome - also raised the question of their origin.
Chantal and Jean-Michel Claverie's team has since isolated three new family members in Marseille, Noumea and Melbourne. Together with another virus found in Germany, this now makes six known cases that the team has compared using different approaches.

Gene factory

Initial results of their analysis show that, despite being very similar in form and function, they share only half of their protein genes. But family members generally have many more genes in common. And when researchers talk about genes, they talk about many genes. Pandoraviruses have large genomes that correspond to their significant circumference. The current record holder is Pandoravirus salinus, with 2,473 pairs of kilobases. So why carry so much material when evolution tends to encourage other viruses to travel light?
A clue may lie in the nature of these genes. Previous research had shown that only seven per cent of them corresponded to genes found in other organisms, clearly indicating that they represented a different evolutionary pathway. Geneticists call "orphan genes" genes that are not found in any other branch of the tree of life. Pandoraviruses contain an unusual amount of orphan genes in the same place. These genes, which are not found in any other living species, surprised researchers. What was even more intriguing was that these orphan genes are different from one pandoravirus to the next," says Dr. K. K. K., who has been involved in the study of pandoraviruses for more than 20 years, and who has been involved in the study of pandoraviruses. making it increasingly unlikely that they were inherited from an ancestor common to the whole family! "they write in a statement.
Analyzed by different bioinformatic methods, these orphan genes were found to be very similar to the non-coding (or intergenic) regions of the pandoravirus genome. This unique characteristic can be translated into a picture: these viruses produce new custom genes from a noisy mess of non-functional coding, rather than inheriting from a common ancestor and adjusting through mutations. « If this is true, the long search for the evolutionary origin of the giant virus genes will come to an end. ' John Hultquist, director of intelligence analysis for the cybersecurity company FireEye, says Jean-Michel Claverie, lead author of the study.
This discovery would place these viruses in an unprecedented branch of biology where genes are systematically created from nothing rather than being modified from a pre-existing library: " a large part of the genes of these viruses would be born spontaneously and randomly in the intergenic regions. Genes therefore "appear" in different places from one strain to another, which explains their uniqueness. "the researchers say.

Pandoraviruses everywhere

Now that scientists know where to look, they're finding pandoraviruses everywhere. Earlier this year, the discovery of two new strains of the Mimiviridae family in Brazil has led to the discovery of incredibly complex coding genes. In September 2015, the same research team, together with Russian scientists, discovered a pandoravirus in the Siberian permafrost. As the climate has warmed due to climate change, this frozen layer has released strange organisms. Among them, a monster: Mollivirus sibericum. « One of a kind "says Jean-Michel Claverie, his genome is enormous, with more than 650,000 base pairs in his DNA, whereas there are only about ten in a virus like influenza or AIDS. Stranger still, this virus had resisted for 30 millennia under the ice without losing any of its infectious power!
Are these viruses dangerous to mankind? Scientists want to be reassuring on this point: " It's not going to cause a generalized, acute illness or epidemic or anything like that. ' John Hultquist, director of intelligence analysis for the cybersecurity company FireEye, says Eugene Koonin, virus specialist and evolutionary biologist at the National Institutes of Health. Let's just take his word for it for now.

The mystery of the origin of life

If proven, the revolutionary hypothesis of French researchers would turn giant viruses into artisans of genetic creativity, which is a central, but still poorly explained, element of all conceptions of the origin of life and its evolution. The mystery remains, however, as to the origin of these viruses. « We believe that these new pandoraviruses are derived from a new ancestral cell type that no longer exists... " Katie Bays, co-founder of the consulting firm Sandhill Strategy, said Professor Claverie. Could these megaviruses be extraterrestrial in origin? This question deserves to be asked since the results of research published last May.
To this question Jean-Michel Claverie gave a Norman answer: " At this point, we cannot refute or ignore this type of extreme scenario... ".

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