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In Giant Virus Genes, Hints About Their Mysterious Origin

In 2003, <em>Acanthamoeba polyphaga mimivirus</em>, also known as mimivirus, was the first giant virus to be described. It's larger than many bacteria, and was found in a water sample from a hospital cooling tower in England.

Viruses are supposed to be tiny and simple — so tiny and simple that it's debatable whether they're even alive.

They're minimalist packets of genetic information, relying entirely on the cells the infect in order to survive and reproduce.

But in 2003, researchers identified a new kind of virus that that turned scientific understanding of viruses upside down, and tested the boundary of what can be considered life.

Mimiviruses, as they're called, are so big and cell-like that samples of them sat on a laboratory shelf for years because scientists assumed they just contained regular old bacteria.

Now, researchers writing in the journal Science say they've found four new species of giant viruses at a wastewater treatment plant in Austria. More importantly, they say, they've found a hint about a persistent question: How these oddballs came to exist in the first place.

"This virus looks much, much more cell-like than any previously discovered one," says Eugene Koonin, an evolutionary biologist at the National Institutes of Health and a co-author on the paper, describing one of the four new viruses.

They're the lumbering Godzillas of the virus world, big enough to see under a regular microscope, although it would still take about 300 of the viruses side by side to reach the width of a human hair.

Koonin and his co-authors propose the four new species are a subfamily of the Mimiviruses, dubbing them the Klosneuviruses. (There are now three other families of giant viruses as well.) And don't worry about getting sick from one of these guys, at least if you're a human. "As far as we know, for the time being, giant viruses only make tiny little creatures sick, like amoebas," Koonin says.

As for the mysterious origins of giant viruses, they found some hints in the genes of the newly discovered Klosneuviruses. After sequencing their genes, Koonin and his colleagues found a surprisingly large number that are involved in copying DNA.

Viruses aren't supposed to have those kinds of genes, especially not such a comprehensive set of them, because they aren't capable of multiplying themselves. It's one reason why they're usually so small, because instead of carrying around all the genetic machinery for replication, they just hijack the machinery of their host cells to replicate.

But if viruses can't reproduce on their own, then what's the point of carrying around a bunch of genetic baggage?

It's unclear. Koonin speculates the genes might help viruses override cells that try to shut down replication when they notice they've been invaded by a virus.

Koonin and his colleagues also compared the newly discovered viruses' DNA-translation genes to a set of genes shared by all giant viruses and to the genes of cells to create an evolutionary tree showing the likely relationships between them.

"When we reconstruct the evolution of these genes, we see that they have very different origins," he says.

Based on that family tree, they conclude that giant viruses likely started out as much smaller viruses, snowballing into giant ones over many generations as they gathered bits and pieces of genetic material from various hosts they infected.

If that's true, it would mean they are like genetic hoarders, collecting lots of genes and rarely throwing any out, until they balloon into virus Godzillas.

Others aren't quite convinced about this explanation for the origin of giant viruses.

"We do think the opposite way. We think that the viruses were complex at the very beginning," says Chantal Abergel, who studies giant viruses at the National Center for Scientific Research in Marseille, France. She wasn't involved in the paper.

According to another hypothesis, giant viruses didn't start small and get big. They started enormous, as actual cellular life forms, and shrank down over time. They might have even originated from a so-called "fourth domain" of life that no longer exists. (The current three domains are Eukarya, which includes us, Archaea and Bacteria).

"We all have questions about how they evolved, what is their origin and how they contributed to life and the evolution of life on Earth," says Abergel. "I don't think anybody has a real answer."

This paper, she points out, focused on a few hundred genes with recognizable functions. But that handful of genes is only a tiny piece of a much bigger picture.

The vast majority of giant virus genes have unknown functions. Koonin calls them "dark matter genes," and those genes, Abergel says, "do not resemble anything in the cellular world or in the viral world."

Rodrigo Araujo Rodrigues, a virologist and evolutionary biologist at the Federal University of Minas Gerais in Brazil, thinks there's compelling evidence for both hypotheses.

"The evidence is quite good," he says, but applying a different method to analyze the genes in Koonin's paper could have produced a different conclusion.

Furthermore the authors of the paper did not isolate the actual viral particles, but instead sequenced all the genes in the wastewater samples and then identified what was inside based on that information. The approach, called metagenomics, is a powerful one.

"But as a virologist that works with evolution, I have to say it's important to have the virus," says Rodrigues.

One thing that everyone in the field can agree on is how dramatically the discovery of giant viruses has turned scientific assumptions upside down.

"The discovery of giant viruses is clearly opening other ways of thinking. Everybody is understanding that we never understood anything about viruses in general," says Abergel. "This is one of the main accomplishments of the discovery of giant viruses, that everything has to be reconsidered."

For example, here's something to chew on: "Giant viruses are the only viruses that can get sick," says Abergel.

They can actually be infected by other viruses.

So, she says, "If you can get sick the question is: Can you be considered alive?"

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