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Mammalian Genomes House Non-Retroviral RNA Virus Sequences, Study Finds

NEW YORK (GenomeWeb News) – An international research team has garnered evidence that bits of non-retroviral RNA viral elements have made their way into mammalian genomes.

A Japanese and American research team searched through mammalian and other sequence databases for sequences resembling the non-retroviral RNA bornaviruses. Indeed, their search turned up endogenous Borna-like N elements, which they dubbed EBLN elements, in the human genome and genomes of other animals including non-human primates, rodents, and the elephant.

The research, which appeared online today in Nature, offer the first evidence of such non-retroviral sequence incorporation into mammalian genomes — and suggests bornaviruses infected some mammalian species tens of millions of years ago.

"Our results provide the first evidence for endogenization of non-retroviral virus-derived elements in mammalian genomes and give novel insights not only into generation of endogenous elements, but also into a role of bornavirus as a source of genetic novelty in its host," senior author Keizo Tomonaga, a virology researcher affiliated with Osaka University and the Japan Science and Technology Agency, and colleagues wrote.

Mammalian genomes are known to contain viral sequences. But so far researchers have only found evidence of retroviral sequences in these genomes.

On the contrary, the new study suggests mammalian genomes also contain non-retroviral RNA from bornaviruses, a group of non-segmented, negative sense RNA viruses.

To find these sequences, the researchers first trolled human protein databases for sequences resembling those found in Borna disease viruses. That search yielded two hypothetical proteins with sequence similarity to the bornavirus structural protein nucleoprotein.

After finding these human homologues, the researchers looked for EBLN elements in other mammalian genomes using tblastn searches of NCBI eukaryote and whole-genome shotgun sequence databases and Southern blot hybridization experiments.

In the process, the team found EBLN orthologues in chimpanzee, gorilla, orangutan, macaque, and other primate genomes. Similar sequences also turned up datasets representing the African elephant, cape hyrax, and several rodent species.

In their subsequent experiments, the team started unraveling the phylogenetic relationships between the EBLNs. They also provided evidence supporting the notion that bornavirus sequences can be copied to DNA and incorporated into the genome.

The researchers' findings suggest EBLN elements have been around in primate genomes for more than 40 million years. In contrast, these elements seem to have become incorporated much more recently in the genome of the thirteen-lined ground squirrel (the only squirrel species in which they found EBLN elements).

Although it's still unclear exactly how these viral elements got into mammalian genomes, the researchers argue that sequence characteristics suggest retrotransposon related reverse transcriptase may have been involved.

And while most EBLNs seem to occur in pseudogenes, the team noted that some of the elements might have functional roles in their host mammalian genomes — a possibility that requires further exploration.

"This report is the first to provide evidence of endogenous sequences derived from a non-retroviral RNA virus in mammalian sequences," the team wrote, adding that the findings imply that bornaviruses are the "first non-retroviral RNA virus whose existence in prehistoric times has been confirmed."