domingo, 4 de março de 2012

Giant Viruses Revive Old Questions About Viral Origins

Vol. 335
no. 6072 p. 1035

University of Aix-Marseille microbiologist Didier Raoult's 2004 discovery of Mimivirus—and several other giant viruses identified since then—has challenged the view that viruses are not alive.
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Even bigger.
Megavirus chilensis (left) strengthened the case that giant viruses share a common ancestor. Didier Raoult believes they form a fourth domain, pictured here in magenta in a drawing from his lab.
Where did viruses come from? And are they alive? Didier Raoult's 2004 discovery of the Mimivirus—and several other giant viruses identified since then—has brought those questions, debated for a century, back to the scientific fore. 

When viruses were discovered in the early 20th century, some scientists saw them as the missing link between the inanimate world and living organisms—a group that predated and perhaps gave rise to cells. But genetic data collected later supported an opposing view, in which viruses emerged from pieces of genetic material and other molecules broken out of cells; they would evolve further by stealing more genes from cellular organisms. This view suggests that viruses aren't part of the tree of life but are an ever-changing sideshow to its three domains: the Archaea, Bacteria, and Eukarya. In 2000, the International Committee on Taxonomy of Viruses officially declared that viruses are not alive.
The genetic makeup of the Mimivirus has challenged this view. The viral giant is endowed with many genes encoding the enzymes that repair DNA, correct errors occurring during its replication, produce mRNA transcripts from genes, and translate those mRNAs into proteins. These so-called informational genes had so far been considered hallmarks of living things. Known viruses hijack the products of these genes from the cells they infect to replicate; the Mimivirus genes had never been found in viruses before. Based on the genome, Raoult and others have concluded that this class of virus has likely inherited its giant genome from an ancient viral ancestor endowed with the entire protein-translation machinery rather than picking up the genes piece by piece.
Not everybody was convinced. In 2008, David Moreira of the University of Paris-Sud in Orsay and his colleagues published an analysis showing that 126 Mimivirus genes have counterparts in cellular organisms, which they said supported the view that, despite its extreme size, Mimivirus has evolved by picking up genes here and there. 

Raoult stuck to his guns, and in a paper published in 2010 proposed a theory that went further: Not only does Mimivirus belong in the tree of life, but nucleocytoplasmic large DNA viruses (NCLDVs), the class to which it belongs, trace their origin to the very beginning of life on Earth, forming a fourth domain alongside the three well-established ones. His view was based on a phylogenetic analysis of eight DNA-processing genes shared by NCLDVs and the three known branches of life, in which the NCLDVs' versions seemed to form a separate cluster. 

But constructing such phylogenies reaching back eons is tricky business, because similarities in genes don't always reflect shared ancestry; the same DNA sequence may have arisen independently in genes of different origins, a process called convergent evolution. In a paper published in June 2011, a team led by Eva Heinz of Newcastle University in the United Kingdom repeated Raoult's analysis but used different models of evolution that take this phenomenon into account. In their phylogenetic trees, the fourth domain evaporated, and the NCLDV genes were spread out over the other branches of life.
For now, Raoult's position in this debate has few supporters. But the idea that giant viruses share ancient common ancestors was bolstered by a paper published in the Proceedings of the National Academy of Sciences last October by Jean-Michel Claverie of the University of Aix-Marseille—once Raoult's collaborator but no longer on speaking terms with him. Claverie recently isolated Megavirus chilensis, a virus distantly related to Mimivirus but even bigger, off the coast of Chile. In the paper, he reported that Megavirus shares 53% of its genes with Mimivirus; of seven genes encoding key steps in protein translation, four have a homolog in Mimivirus and had never been found in a virus before. “This rules out the scenario whereby those genes were acquired independently by both viruses,” Claverie says. Even Moreira says the paper won him over for a common viral ancestor between the two viruses. 

Edward Holmes, a virus evolution specialist at Pennsylvania State University, University Park, notes that ongoing fishing expeditions for new viruses—not just the giant ones—are likely to resolve the origins of these infectious agents. “It's naïve to say that we understand the history of the evolution of viruses based on current samples,” Holmes says. “There may be undiscovered viruses on our planet, some completely novel.”

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