Go to content

You are here:

Endogenous Non-Retroviral RNA Virus elements in Mammalian Genomes

Masayuki Horie1*, Tomoyuki Honda1,2*, Yoshiyuki Suzuki3, Yuki Kobayashi3, Takuji Daito1, Tatsuo Oshida4, Kazuyoshi Ikuta1, Patric Jern5, Takashi Gojobori3, John M. Coffin5 & Keizo Tomonag

 

Letter

Nature 463, 84-87 (7 January 2010) | doi:10.1038/nature08695; Received 2 September 2009; Accepted 17 November 2009

Endogenous non-retroviral RNA virus elements in mammalian genomes

Masayuki Horie1,7, Tomoyuki Honda1,2,7, Yoshiyuki Suzuki3, Yuki Kobayashi3, Takuji Daito1, Tatsuo Oshida4, Kazuyoshi Ikuta1, Patric Jern5, Takashi Gojobori3, John M. Coffin5 & Keizo Tomonaga1,6

  1. Department of Virology, Research Institute for Microbial Diseases (BIKEN), Osaka University, Osaka 565-0871, Japan
  2. Japan Society for the Promotion of Science (JSPS), Chiyoda-ku, Tokyo 102-8472, Japan
  3. Center for Information Biology and DNA Data Bank of Japan, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan
  4. Department of Life Science and Agriculture, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido 080-8555, Japan
  5. Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA
  6. PRESTO, Japan Science and Technology Agency (JST), Chiyoda-ku, Tokyo 102-0075, Japan
  7. These authors contributed equally to this work.

Correspondence to: Keizo Tomonaga1,6 Correspondence and requests for materials should be addressed to K.T. (Email: tomonaga@biken.osaka-u.ac.jp).

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.