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Metagenomic Study Uncovers Apparent RNA-DNA Hybrid Virus

NEW YORK (GenomeWeb News) – Results from a metagenomic study described online today in the journal Biology Direct are challenging the notion that viruses exchange sequences exclusively with viruses of the same type.

A pair of researchers from Portland State University sifted through Roche 454 sequences generated from DNA in samples from Lassen Volcanic National Park's Boiling Springs Lake in northeastern California as part of a metagenomics study of viral diversity in the hot, acidic lake.

One virus in particular caught their attention: the large circular, single-stranded virus, since dubbed BSL RDHV, which had many typical DNA virus features. But it also contained a capsid protein-coding sequence that had previously been found only in RNA viruses that aren't converted to DNA at any stage of their replication.

The apparent DNA-RNA hybrid has left the study's authors speculating about how many yet undiscovered viruses have resulted from sequence swaps between seemingly unrelated viral groups, as well as the role that this far-reaching recombination might have in viral evolution overall.

"The discovery that novel virus groups can emerge via recombination between highly disparate virus types will have broad implications for the early evolution of viruses," according to the study's corresponding author Kenneth Stedman, a biologist with Portland State University's Center for Life in Extreme Environments.

In a statement, Stedman said the work "extends the modular theory of virus evolution to encompass a much broader range of possibilities than previously thought."

In general, viruses belong to three groups, Stedman and co-author Geoffrey Diemer explained, comprised of DNA viruses, RNA viruses, and RNA retroviruses, which morph into DNA via reverse transcription during certain stages of infection. While it has been appreciated for some time that viruses can trade genetic material back and forth, this lateral gene transfer was thought to be limited to viruses of the same type.

On the contrary, though, Stedman and Diemer found characteristic single-stranded DNA virus sequences directly neighboring a capsid protein-coding gene normally seen in single-stranded RNA viruses when they began analyzing and assembling virus-sized particle sequences from Boiling Springs Lake samples.

Samples from the lake — an acidic environment where temperatures range from 52 to 95 degrees Celsius (125˚F to 203˚F) — had been generated on the Roche 454 GS FLX Titanium platform at the Broad Institute through an effort funded by the Gordon and Betty Moore Foundation's Marine Microbiology Initiative.

Through follow-up experiments using inverse PCR and Sanger sequencing, the Portland researchers verified the genome sequence for the new virus, BSL RDHV.

Their subsequent analyses of the genome indicated that it has features resembling those in other DNA "circoviruses," though it is much larger and also includes a gene for the capsid protein usually found in a group of ssRNA viruses called tombuviruses.

When they scoured viral sequence databases, the team found BSL RDHV-like sequences in data collected by the Global Ocean Survey, along with a few candidate viruses that apparently share genome features with BSL RDHV, hinting that similar viral hybrids exist elsewhere.

"As more viral metagenomic data are generated and analyzed, additional evidence of recombination between RNA and DNA virus groups will likely be discovered," Stedman said.

While the study authors speculated that such hybrid DNA-RNA viruses might arise through a combination of reverse transcription and recombination, they emphasized that more research will be needed to understand how BSL RDHV nabbed the capsid coding sequence from RNA viruses and to appreciate the broader significance of this exchange.

"This unique viral genome carries implications for theories of virus emergence and evolution," they wrote, "as no mechanisms for inter-viral RNA-DNA recombination has yet been identified, and only scant evidence exists that genetic exchange occurs between such distinct virus lineages."

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