Hunting Fossil Viruses in Human DNA
Hunting Fossil Viruses in Human DNAHunting Fossil Viruses in Human DNA
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EVOLVED Fossil viruses are helping to shed light on the deep history of viruses like HIV, shown above with red triangular cores of RNA material.
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The virus now turns out to have an intimate bond with every person on Earth. In the latest issue of Nature, a team of Japanese and American scientists report that the human genome contains borna virus genes. The virus infected our monkey-like ancestors 40 million years ago, and its genes have been passed down ever since.
Borna viruses are not the only viruses lurking in our genome. Scientists have found about 100,000 elements of human DNA that probably came from viruses. But the borna virus belongs to a kind of virus that has never been found in the human genome before. Its discovery raises the possibility that many more viruses are left to be found.
Scientists who hunt for these viruses think of themselves as paleontologists searching for fossils. Just as animals get buried in rock, these viruses become trapped in the genomes of their hosts. While their free-living relatives continue to evolve, fossil viruses are effectively frozen in time.
“We can really dig fossils out of the genome and literally put them back together,” said Cédric Feschotte, a genome biologist at the University of Texas, Arlington. “It’s like putting a hominid back together and asking it if it can walk upright.”
When scientists sequenced the human genome in 2001, they noticed many segments that bore a striking resemblance to genes in retroviruses, a class of viruses that includes H.I.V.
Retroviruses carry their genetic material in a single-stranded version of DNA, called RNA. To make new viruses, they make DNA versions of their genes, which are inserted into a host cell’s genome. The cell then reads the retrovirus’s genes as if they were its own, and manufactures new retroviruses.
Scientists speculated that every now and then a retrovirus inserted itself into a host cell and then failed to turn it into a virus factory. If the trapped retrovirus happened to be in sperm or egg cells, its DNA might be passed down to the host’s descendants. From generation to generation, the virus’s DNA would mutate. It would lose its ability to produce normal viruses. For a while it might be able to make new viruses that could re-infect the same cell, but over enough time, the viruses would become disabled.
In recent years, scientists have found several lines of evidence to support this idea. . Koala retroviruses, for example, appear to be in the middle of the journey. The viruses can move from one koala to another. But in some populations of koalas, the virus’s DNA is permanently lodged in their genomes.
Thierry Heidmann of the Gustave Roussy Institute in France and his colleagues put the fossil virus hypothesis to a spectacular test: they tried to resurrect a dead retrovirus. They first identified a number of copies of the same virus-like stretch of DNA in the human genome. Each version had its own set of mutations that it acquired after the virus had invaded our ancestors.Hunting Fossil Viruses in Human DNA Hunting Fossil Viruses in Human DNA
By comparing the copies, Dr. Heidmann and his colleagues were able to figure out what the original sequence of the virus’s genes had been. When they synthesized the genes from scratch and injected the genetic material into cells, the cells produced new viruses.Hunting Fossil Viruses in Human DNA
“It was a tour-de-force of an experiment,” said John Coffin, an expert on fossil viruses at Tufts University.
Now fossil virus hunters are moving beyond the human genome. They’re taking advantage of the growing number of mammal genomes piling up in online databases and helping to flesh out the evolutionary history of viruses, reaching back tens of millions of years. Aris Katzourakis, an evolutionary biologist at the University of Oxford, and his colleagues recently went on a hunt for fossils of foamy viruses in mammals. Foamy viruses infect some mammals, including monkeys and apes. Primate foamy viruses can infect humans harmlessly, but researchers fear they may evolve to become dangerous. Dr. Katzourakis and his colleagues discovered hundreds of foamy virus copies in the DNA of the two-toed sloth. They then found the same virus lurking in the genome of the three-toed sloth. Before Dr. Katzourakis’s fossil hunt, scientists had never found a foamy virus infecting any sloths, or any of their relatives like armadillos and anteaters.
Sloths and their relatives branched off from all other placental mammals about 100 million years ago. Dr. Katzourakis’s discovery thus reveals the great antiquity of foamy viruses. They were already infecting the common ancestor of all placental mammals back when dinosaurs ruled the Earth.Hunting Fossil Viruses in Human DNA
These fossils are also offering clues to how viruses evolved. Dr. Katzourakis and his colleagues have found fossil viruses that are helping shed light on the deep history of H.I.V., for example.
H.I.V. evolved about a century ago from a chimpanzee virus known as simian immunodeficiency virus, or S.I.V. Many apes and monkeys carry their own strain of S.I.V, but it’s not clear how long the viruses have been infecting primates.
In 2008, Dr. Katzourakis and his colleagues discovered fossil S.I.V. in the genome of the gray lemur, a primate that lives in Madagascar. Last May, Dr. Feschotte and his colleagues reported that they had found the same fossil virus in the fat-tailed lemur.
Scientists had never before found S.I.V. in lemurs, which branched off from all other living primates some 50 million years ago. The fossil virus is also missing one of the genes found in all other forms of S.I.V. and H.I.V. It may be a transitional form of the virus, akin to the fossils paleontologists have found of feathered dinosaurs that couldn’t fly.
Fossil viruses are also illuminating human evolution. Scientists estimate that 8.3 percent of the human genome can be traced back to retrovirus infections. To put that in perspective, that’s seven times more DNA than is found in all the 20,000 protein-coding genes in the human genome.
But that figure may be too low, according to Dr. Katzourakis. “The measurable diversity of viruses may go up, and the true diversity may be much higher,” he said.