Endogenous Retroviral Sequences; Their Evolutionary Contribution to the Human Genome


Endogenous retroviruses (ERVs) comprise approximately 8% of the human genome. They stem from germ cell invasions of exogenous retroviruses in the evolutionary past. Human ERV transcripts are found in every human tissue, and their expression patterns seem to be regulated by complex mechanisms. HERV transcription is often deregulated in diseased tissue and cells. By introducing numerous regulatory elements into the genome ERVs profoundly influence quite a number of cellular genes regarding gene structure and expression patterns. Although most ERV sequences in the human genome are coding defective, some HERVs still encode proteins that appear to have become essential human genes or that appear to be involved in human diseases. A HERV encoded protein is essentially involved in placenta development. Other HERV encoded proteins may serve as biomarkers for certain tumour types or may be involved in tumour development.

Key Concepts:

  • Most vertebrate genomes harbour significant amounts of repetitive sequences.

  • Human endogenous retroviruses are remnants of ancient retroviral infections of the germ line.

  • Approximately 8% of the human genome are of retroviral origin.

  • HERV sequences are often severely mutated due to longā€time presence in the genome.

  • HERV transcripts are found in every human tissue.

  • HERV transcription is deregulated in some diseases including tumours.

  • HERV loci can influence transcription of nearby genes.

  • A HERV encoded protein is essentially involved in placental development.

  • Other HERV proteins may be involved in tumour development.

Keywords: endogenous retrovirus; repetitive sequence; provirus; gene structure; genome evolution

Figure 1.

Typical provirus structure and variants of HERV proviruses. A provirus usually includes coding regions for gag, protease (pro), polymerase (pol) and envelope (env) that are flanked on each side by a Long Terminal Repeat (LTR). Although a number of HERV loci in the human genome still display the complete proviral structure, most HERV loci carry internal deletions within the coding regions, or lack 5′ or 3′ portions entirely (deletions depicted as dotted lines). Especially for older HERVs, other mobile elements, including other retroviral sequences, often formed new copies within existing HERV loci. Homologous recombination events within proviral loci often resulted in so‐called solitary LTR (bottom).

Figure 2.

Examples of effects of endogenous retroviral sequences on cellular genes. Provirus formation within a gene can result in, for instance, altered splicing patterns due to usage of proviral splice sites, premature termination of transcripts due to usage of proviral polyA signals and alternative initiation of gene transcripts due to promoter activity within proviral LTRs. Regulatory sequences within LTRs can also influence a gene's actual promoter (depicted by dashed arrow). See text for examples.



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Web Links

C‐GATE Catalogue of genes affected by transposable elements https://sites.google.com/site/tecatalog/

Genome Browser An intuitive browser for the human and other genomes that also depicts (H)ERV distribution http://genome.ucsc.edu/

Repbase A reference sequence database for repetitive elements http://www.girinst.org/

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How to Cite close
Mayer, Jens(Mar 2013) Endogenous Retroviral Sequences; Their Evolutionary Contribution to the Human Genome. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0020825.pub2]