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Bornavirus DNA Seen as Possible Source of Human Mutation Print E-mail
SciMed - Biology
TS-Si News Service   
Saturday, 09 January 2010 16:00

Bornavirus DNA Isolated as Possible Source of Human Mutation

Arlington, TX, USA. In an evolutionary surprise, about eight percent of human genetic material comes from a virus and not from our ancestors, according to researchers in Japan and the U.S.

This virally transmitted DNA may be a cause of mutation and psychiatric disorders such as schizophrenia and mood disorders.

The research showed that the genomes of humans and other mammals contain DNA derived from the insertion of bornaviruses, RNA viruses whose replication and transcription takes place in the nucleus.

The assimilation of viral sequences into the host genome is a process referred to as endogenization. This occurs when viral DNA integrates into a chromosome of reproductive cells and is subsequently passed from parent to offspring. Until now, retroviruses were the only viruses known to generate such endogenous copies in vertebrates.

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Two related papers that appear in the journal Nature, are authored by Professor Keizo Tomonaga at Osaka University [C1] and biology professor Cédric Feschotte at the University of Texas (Arlington). [C2]

Keizo Tomonaga

In his article, Feschotte speculates about the role of such viral insertions in causing mutations with evolutionary and medical consequences. Feschotte said that scientists have found that non-retroviral viruses called bornaviruses have been endogenized repeatedly in mammals throughout evolution.

Cedric Feschotte

Borna disease virus (BDV) owes its name to the town of Borna, Germany, where a virus epidemic in 1885 wiped out a regiment of cavalry horses BDV causes abnormal behaviour and fatality.

Recent findings have implicated the virus in some human neurological and psychiatric conditions including bipolar disorder and depression..

BDV infects a range of birds and mammals, including humans.

The bornavirus It is unique because it infects only neurons, establishing a persistent infection in its host's brain, and its entire life cycle takes place in the nucleus of the infected cells.

Feschotte said this intimate association of BDV with the cell nucleus prompted researchers to investigate whether bornaviruses may have left behind a record of past infection in the form of endogenous elements. They searched the 234 known eukaryotic genomes (those genomes that have been fully sequenced) for sequences that are similar to that of BDV. "The researchers unearthed a plethora of endogenous Borna-like N (EBLN) elements in many diverse mammals, " Feschotte said.

The scientists also were able to recover spontaneous BDV insertions in the chromosomes of human cultured cells persistently infected by BVD.Based on these data, Feschotte proposes that BDV insertions could be a source of mutations in the brain cells of infected individuals.

"These data yield a testable hypothesis for the alleged, but still controversial, causative association of BDV infection with schizophrenia and mood disorders," Feschotte said. The research in Feschotte 's laboratory largely focuses on transposable elements, the genetic elements that are able to move and replicate within the genomes of virtually all living organisms.

Citation[C1] Endogenous non-retroviral RNA virus elements in mammalian genomes. Masayuki Horie, Tomoyuki Honda, Yoshiyuki Suzuki, Yuki Kobayashi, Takuji Daito, Tatsuo Oshida, Kazuyoshi Ikuta, Patric Jern, Takashi Gojobori, John M. Coffin and Keizo Tomonaga. Nature 2010; 463(7277): 84-87. doi:10.1038/nature08695

Abstract

Retroviruses are the only group of viruses known to have left a fossil record, in the form of endogenous proviruses, and approximately 8% of the human genome is made up of these elements1, 2. Although many other viruses, including non-retroviral RNA viruses, are known to generate DNA forms of their own genomes during replication3, 4, 5, none has been found as DNA in the germline of animals. Bornaviruses, a genus of non-segmented, negative-sense RNA virus, are unique among RNA viruses in that they establish persistent infection in the cell nucleus6, 7, 8. Here we show that elements homologous to the nucleoprotein (N) gene of bornavirus exist in the genomes of several mammalian species, including humans, non-human primates, rodents and elephants. These sequences have been designated endogenous Borna-like N (EBLN) elements. Some of the primate EBLNs contain an intact open reading frame (ORF) and are expressed as mRNA. Phylogenetic analyses showed that EBLNs seem to have been generated by different insertional events in each specific animal family. Furthermore, the EBLN of a ground squirrel was formed by a recent integration event, whereas those in primates must have been formed more than 40 million years ago. We also show that the N mRNA of a current mammalian bornavirus, Borna disease virus (BDV), can form EBLN-like elements in the genomes of persistently infected cultured cells. 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.



[C2] Virology: Bornavirus enters the genome. Cédric Feschotte. Nature 2010; 463: 39-40. doi:10.1038/463039a

Abstract

A survey of mammalian genomes has unexpectedly unearthed DNA derived from bornaviruses, leading to speculation about the role of these viruses in causing mutations with evolutionary and medical consequences.

Some people might find it disquieting that a hefty 8% of human genetic material originates not from our vertebrate ancestors but from viruses. The assimilation of viral sequences into the host genome is a process referred to as endogenization.

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Last Updated on Friday, 08 January 2010 23:25