pubmed.ncbi.nlm.nih.gov

Identification of endogenous retroviral reading frames in the human genome - PubMed

  • ️Thu Jan 01 2004

Identification of endogenous retroviral reading frames in the human genome

Palle Villesen et al. Retrovirology. 2004.

Abstract

Background: Human endogenous retroviruses (HERVs) comprise a large class of repetitive retroelements. Most HERVs are ancient and invaded our genome at least 25 million years ago, except for the evolutionary young HERV-K group. The far majority of the encoded genes are degenerate due to mutational decay and only a few non-HERV-K loci are known to retain intact reading frames. Additional intact HERV genes may exist, since retroviral reading frames have not been systematically annotated on a genome-wide scale.

Results: By clustering of hits from multiple BLAST searches using known retroviral sequences we have mapped 1.1% of the human genome as retrovirus related. The coding potential of all identified HERV regions were analyzed by annotating viral open reading frames (vORFs) and we report 7836 loci as verified by protein homology criteria. Among 59 intact or almost-intact viral polyproteins scattered around the human genome we have found 29 envelope genes including two novel gammaretroviral types. One encodes a protein similar to a recently discovered zebrafish retrovirus (ZFERV) while another shows partial, C-terminal, homology to Syncytin (HERV-W/FRD).

Conclusions: This compilation of HERV sequences and their coding potential provide a useful tool for pursuing functional analysis such as RNA expression profiling and effects of viral proteins, which may, in turn, reveal a role for HERVs in human health and disease. All data are publicly available through a database at http://www.retrosearch.dk.

PubMed Disclaimer

Figures

Figure 1
Figure 1

A: Genomic organization of simple retroviruses when present as a provirus (DNA) integrated in the host genome. The regulatory long terminal repeats (LTRs) flank the internal three major genes gag, pol and env. A fourth gene pro is present between gag and pol for some retroviruses, while part of either gag or pol in others. B: Individual BLAST hits (white and yellow boxes) on either strand of the human genome were clustered into HERV regions (blue boxes) or discarded by using a score function. Finally, only HERV regions with at least one retroviral ORF were kept (see Materials and Methods). In the example illustrated HERV ID 5715 was presumably inserted into an existing HERV locus with the opposite orientation. HERV ID 5715 is located in the first intron of the CD48 gene (antisense direction) and is also known as HERV-K18 or IDDMK1,222. C: HERV ID 5715 with graphical vORF annotation. Putative LTR structures are indicated and all ORFs (stop-codon to stop-codon fragments above 62 aa) are mapped and annotated by homology criteria

Figure 2
Figure 2

Number of HERV regions located inside genes, and their orientation relative to the gene. The expected number assumes a random genomic distribution.

Figure 3
Figure 3

Genomic distribution of all Gag (red) and Env (blue) ORFs above 500 aa and Pol (green) ORFs above 700 aa. Right-pointing triangles denote intact ORFs, while left-pointing triangles denote ORFs that are almost-intact besides a single stop codon or frame-shift mutation.

Similar articles

Cited by

References

    1. International Human Genome Sequencing Consortium (IHGSC) Initial sequencing and analysis of the human genome. Nature. 2001;409:860–921. doi: 10.1038/35057062. - DOI - PubMed
    1. Tristem M. Identification and characterization of novel human endogenous retrovirus families by phylogenetic screening of the Human Genome Mapping Project database. J Virol. 2000;74:3715–3730. doi: 10.1128/JVI.74.8.3715-3730.2000. - DOI - PMC - PubMed
    1. Benit L, Dessen P, Heidmann T. Identification, phylogeny, and evolution of retroviral elements based on their envelope genes. J Virol. 2001;75:11709–11719. doi: 10.1128/JVI.75.23.11709-11719.2001. - DOI - PMC - PubMed
    1. Jurka J. Repbase update: A database and an electronic journal of repetitive elements. Trends Genet. 2000;16:418–420. doi: 10.1016/S0168-9525(00)02093-X. - DOI - PubMed
    1. Paces J, Pavlicek A, Zika R, Kapitonov VV, Jurka J, Paces V. HERVd: the Human Endogenous RetroViruses Database: update. Nucleic Acids Res. 2004;32:D50. doi: 10.1093/nar/gkh075. - DOI - PMC - PubMed

Publication types

MeSH terms

Substances