With the aid of advanced gene sequencing, comparative DNA analysis,and endless cross-referencing of the genomes of organisms from the three—or perhaps four—domains of life, a fuller concept of viruses and their role in evolution has begun to coalesce. In the mere year and a half since Bradfordcoccus's true identity was revealed, more genetically distinct and extremely ancient viruses have been found. All of them lead scientists to the same conclusion: Evolution's archvillain looks more and more like its vital and formative force.
Even as Darwinism has come under attack from the theology of the intelligent design movement, scientists have never been closer to divining life's origins. With DNA evidence as solid as that used to convict criminals, researchers can trace the shared genetic lineage of life's different branches back to the very base of the tree, some 4 billion years ago, when the interaction between primordial bacteria and viruses culminated in the "mother cell," the common ancestor of all life on Earth. Although the remoteness and complexity of those events makes them difficult to piece together, viruses like Mimi are emerging as the key players in the picture.
"We are now able to draw a tree of life for the first time that includes viruses as their own branch," says Patrick Forterre, a molecular biologist at the University of Paris-Sud.
Last July Forterre held a weeklong conference in Les Treilles, France, where two dozen of the world's leading microbiologists, cell biologists, and evolutionary biologists met to discuss "The Origin of the Nucleus." The nucleus, the command-and-control center of the eukaryotic cell, is ultimately what distinguishes a human from a bacterium. For eons prior to the emergence of the nucleated cell, life on Earth was essentially slime: vast, directionless mats of single-celled bacteria and archaea.
With no nucleus to further modify and craft gene expression and protein translation, life thrived but literally could not get hold of itself, could not assume new shapes or diversify. How the first nucleus came to be is a question that has intrigued scientists ever since Scottish botanist Robert Brown first detected a cell nucleus while peering at orchids under a microscope one day in 1824.
The discovery of Mimivirus lends weight to one of the more compelling theories discussed at Les Treilles. Back when the three domains of life were emerging, a large DNA virus very much like Mimi may have made its way inside a bacterium or an archaean and, rather than killing it, harmlessly persisted there. The eukaryotic cell nucleus and large, complex DNA viruses like Mimi share a compelling number of biological traits. They both replicate in the cell cytoplasm, and on doing so, each uses the same machinery within the cytoplasm to form a new membrane around itself. They both have certain enzymes for capping messenger RNA, and they both have linear chromosomes rather than the circular ones typically found in a bacterium.
"If this is true," Forterre has said of the viral-nucleus hypothesis, "then we are all basically descended from viruses."
Claverie says, "That's quite a big jump in our thinking about viruses—to go from their not even being organisms to being all life's ancestor."
Some scientists go a step further. They believe that viruses played a role even earlier in the evolutionary mix. The precise order in which the three domains of life evolved—whether, say, the eukaryotes emerged before or after the archaea and bacteria—is a much-debated subject. So is the identity of the progenitor of those different domains, the so-called last universal common ancestor, or LUCA, as it was dubbed by Forterre at the first Les Treilles conference in 1996.
"I'm probably one who has asserted most sternly that LUCA was viral," says Luis Villarreal, the director of the Center for Virus Research at the University of California at Irvine. "The genes and gene functions suggest that we're dealing with one of the earliest and oldest forms of life. Mimivirus really stretches our sense of scale of what a virus can be."
But just how far can that scale be stretched? David Prangishvili, a virologist at the Pasteur Institute in Paris and a colleague with Forterre in studying viruses that infect archaea, now thinks that viruses swam in the primordial soup prior to the emergence of cellular life of any kind and only later became dependent on cells. Forterre is less convinced.
"It is difficult for me to imagine," he says. "You need to have some type of closed system to be sure that the different reactants of the metabolism, or different mechanisms, can interact with each other and also have a kind of Darwinian evolution. You need to have individuals. I think there was an RNA world prior to the DNA world, when you had a lot of RNA cells. Maybe viruses originated at the time of the RNA cell. You need to have a cell to even obtain a virus."
Yet to virologists like Prangishvili and Villarreal, the concept of viruses as the primordial soup's first built-in stirrers seems to align perfectly with their nature: high creative replication, genetic reproduction, and sorting of gene fragments, not to mention their eerie biochemical straddle between life and non life.
"I think what confuses people is their assumption that parasites are only damaging things," says Villarreal. "How do you get creation and complexity out of them? You do because they persist, and to do that you have to take on all comers. You come up with inventions that prevent you from being displaced. It's no surprise that the number-one-selling software on the planet these days claims to be 'antiviral.' "
Information, whether biological or industrial, is passed along by replication. Create a new word-processing file and copy it: that's replication. But any replication process is susceptible to errors, which in turn can generate novelty. And novelty, especially in harsh, shifting conditions like those that prevailed on the newly formed Earth, is often an advantage: Some new life-forms will adapt better to the environment. To the utter abhorrence of the proponents of intelligent design, there is a certain randomness to evolution.
Some viruses, like Ebola or the new avian influenza, are basically runaway replicators, effectively burning their own life bridges in the process. But the majority, as Villarreal puts it, strive "to persist, not make a lot." Those that do persist eventually become both stable within, and staples of, evolution. The overwhelming majority of viruses are not harmful to their hosts. Each of us is infected with a huge array of viruses. The human genome, considered as a mass, contains more retrovirus sequences than actual genes.
"They're not doing anything," says Villarreal. "They're just persisting. And they were around long before humans evolved. The better part of the human genome is composed of viral DNA. That's true of nearly all eukaryotes, and the more complicated the organisms, the more of those sequences you have. We aren't sure exactly what they all do, but they are part of our genetic identity, this stuff we dismiss as junk. 'Junk' and 'parasite' are both words that will get you into a fight if you use them improperly. And yet they are where all life's creativity lies—its very origins."
What was the very first bit of life's biochemical code, and where did it come from? It may be no surprise to learn that viruses figure ever more prominently into this line of speculation. Some researchers go so far as to suggest that the very first life on Earth could have arrived in the form of a viral shard from afar, perhaps conveyed in the pore of a meteorite.
"Well, I used to laugh at the idea," says Mark Young, a Montana State University biologist who leads a research team that gathers new archaeal viruses from superhot aquatic environments in Yellowstone National Park and other places around the world. "But I wouldn't say it's absurd anymore. I think it has to at least be kept in the portfolio of the discussion."
Where researchers do agree is that a nearly immeasurable array of viruses remain to be discovered on this planet. A growing number of virologists and biologists are out to catalog them. Both Claverie's and Raoult's labs have already begun searching for more viruses like Mimivirus. Among the most likely sites are algae, the ocean, and of course, cooling towers. Claverie says he sees no good reason why there can't be viruses bigger than Mimi.
"I'm hoping Mimi isn't the only one of its kind on Earth," he says, "especially since that cooling tower in Bradford has been destroyed. But it can't be the only one. That would be ridiculously lucky for it to have just fallen into our lap."
Meanwhile, Young has been finding new archaeal viruses every time he looks for them. Asked why Mimivirus hadn't been discovered sooner, he says it may come down to the simple fact that we just haven't been looking.
"We haven't even begun to scratch the surface. The numbers are mind-boggling. If you put every virus particle on Earth together in a row, they would form a line 10 million light-years long. People, even most biologists, don't have a clue. The general public thinks genetic diversity is us and birds and plants and animals and that viruses are just HIV and the flu. But most of the genetic material on this planet is viruses. No question about it. They and their ability to interact with organisms and move genetic material around are the major players in driving speciation, in determining how organisms even become what they are."
We have been looking for our designer in all the wrong places. It seems we owe our existence to viruses, the least of semi-living forms,and about the only thing they have in common with any sort of theological prime mover is their omnipresence and invisibility. Once again, viruses have altered the way that we view them and, by extension, ourselves. As it turns out, they are not the little breakaway shards of our biology—we are, of theirs.