Posted by Bob Grant

[Entry posted at 6th January 2010 06:00 PM GMT]

 

Traces of genetic material from non-retroviruses have unexpectedly turned up in the genomes of several mammal species, including humans.

Image: National Human Genome Research Institute

Researchers report in this week's issue of Nature that bornaviruses, a group of negative sense RNA viruses, integrated into the DNA of humans and other primates, rodents, and elephants millions of years ago. These snippets represent a source of additional mutation in the mammal genomes they inhabit and a potential source of genomic innovation, the authors suggest.

The researchers have "found an unforeseen source of mutation that not many people had thought about before," said C?dric Feschotte, a genomicist at the University of Texas, Arlington, who was not involved with the study.

While about eight percent of human DNA is derived from retroviruses that invaded the genome of our ancient ancestors, this is the first evidence of a non-retrovirus stably incorporating its genetic material into the genome of its host.

The results also bring more resolution to science's understanding of viral evolution, pushing back the date of bornavirus' appearance on the evolutionary scene. "This tells us that these viruses were around and not that different from the ones we have today many, many millions of years ago," said paper coauthor John Coffin, a molecular virologist at Tufts University in Boston.

Feschotte, who wrote an accompanying commentary in this week's Nature, also told The Scientist that the findings raise many questions about how and why bornaviruses integrated their RNA into the DNA of mammals in the distant past. Unlike retroviruses, which must integrate into host DNA in order to replicate and use their own molecular machinery to do so, bornaviruses can replicate without genomic integration and therefore lack the machinery to do so, Feschotte explained.

This is just one of leads suggested by the research, Coffin noted. "The most interesting question to me is, 'Have these [endogenous bornavirus-like elements] acquired some useful function in the genome?'" Indeed, two of the four elements, which all bear a resemblance to the N gene of bornavirus, are annotated as protein-coding genes in the human genome. "These may be fulfilling some useful function," such as fending off infection from related viruses, as is the case with many of the endogenous retrovirus genes found in the human genome, Coffin said.

Coffin and his colleagues, led by Japanese researcher Keizo Tomonaga, searched through 234 currently available eukaryotic genomes and found borna-like elements integrated into the genomes of mammals from ground squirrels and elephants to orangutans and humans. The authors suggest that the initial integration in primates occurred more than 40 million years ago, while the event happened much more recently -- about 10 million years ago -- in squirrels.

Though this is the first instance of non-retrovirus genetic material cropping up in the genomes of their hosts, the phenomenon is likely to be more widespread. "I hope that this will stimulate people with interest in other viruses to go looking with gun and camera through the published genomes," said Coffin, adding that he also expects researchers to find endogenous bornavirus elements in the genomes of birds, which also play host to bornaviruses. "There may be much more out there waiting to be found."

Feschotte agreed. "This may just be the tip of the iceberg," he said.