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What contemporary viruses tell us about evolution: a personal view.

Moelling K - Arch. Virol. (2013)

Bottom Line: Viruses helped in building genomes and are driving evolution.Only in unbalanced situations do viruses cause infectious diseases or cancer.Are viruses our oldest ancestors?

View Article: PubMed Central - PubMed

Affiliation: Max Planck Institute for Molecular Genetics, Ihnestr 63-73, 14195, Berlin, Germany. moelling@imm.uzh.ch

ABSTRACT
Recent advances in information about viruses have revealed novel and surprising properties such as viral sequences in the genomes of various organisms, unexpected amounts of viruses and phages in the biosphere, and the existence of giant viruses mimicking bacteria. Viruses helped in building genomes and are driving evolution. Viruses and bacteria belong to the human body and our environment as a well-balanced ecosystem. Only in unbalanced situations do viruses cause infectious diseases or cancer. In this article, I speculate about the role of viruses during evolution based on knowledge of contemporary viruses. Are viruses our oldest ancestors?

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Related in: MedlinePlus

Endogenous retroelements (RE). (Top) A virus in a virus in a virus can be detected in cellular genes. One example is shown here with a protein kinase B inhibitor gene, which consists of up to 85 % REs [13, 59]. An integrated HERV-K(C4) is indicated. The inserts accumulate within introns, where integrations are less harmful than they would be in exons (Ex). REs comprise retroviruses and shorter versions, LINE, SINE or only LTRs [19]. (Left) The human endogenous retroviruses (HERV-K (C4)) can influence regulation of other genes, as shown for DAP3, a proapoptotic gene [13]. Antisense transcripts can shut off sense transcripts of a tumor suppressor gene and can thereby cause cancer. (Right) The number of human REs is shown as segments [modified from ref. 9]. The white area is investigated by ENCODE project
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Fig6: Endogenous retroelements (RE). (Top) A virus in a virus in a virus can be detected in cellular genes. One example is shown here with a protein kinase B inhibitor gene, which consists of up to 85 % REs [13, 59]. An integrated HERV-K(C4) is indicated. The inserts accumulate within introns, where integrations are less harmful than they would be in exons (Ex). REs comprise retroviruses and shorter versions, LINE, SINE or only LTRs [19]. (Left) The human endogenous retroviruses (HERV-K (C4)) can influence regulation of other genes, as shown for DAP3, a proapoptotic gene [13]. Antisense transcripts can shut off sense transcripts of a tumor suppressor gene and can thereby cause cancer. (Right) The number of human REs is shown as segments [modified from ref. 9]. The white area is investigated by ENCODE project

Mentions: This was unexpected when it was discovered while sequencing the human genome [59]. On average, flies, worms and plants only contain 3-10 % transposable elements in their genomes [59]. Among the human TEs, there are about 450,000 retrovirus-like elements [59]. Infection of germline cells led to the accumulation of viral genes during evolution and made the human genome a “graveyard” of retroviral fossils. The host developed mechanisms to suppress such genes in the germline by silencing viral promoters through epigenetic modifications, e.g., DNA methylation. Mutations can likewise prevent protein expression and particle formation, yet these elements may affect host cell functions [51]. The significance of these TEs has been a fertile topic for speculation among biologists. Is it “junk DNA” [6]? Since this DNA can be transcribed into non-coding RNA (ncRNA) with gene regulatory function, it cannot simply be “junk.” The recent ENCODE (encyclopedia of DNA elements) project designated these regions as “deserts” – because of their lack of information, but important functions have now been suggested for these regions as well, especially for human diseases and gene regulation [7]. We also observed this when we studied a full-length human endogenous retrovirus HERV, which entered the human genome 35 Mio years ago, as calculated from the divergence between the two LTRs at the ends of the DNA provirus [13]. The viral promoter within the LTR is normally silenced by the antiviral response of the host cell. However, it can be activated by metabolic stress. If the activated LTR allows a transcript in the opposite direction to the transcript of a neighboring cellular gene, it is downregulated, and when it is expressed in parallel, it is upregulated. One such downregulated gene that we identified recently as a tumor suppressor gene is involved in apoptosis. LTR-driven antisense transcription resulted in prevention of apoptosis and cancer formation [13] (Fig. 6). Thus, 35-Mio-year-old endogenous HERVs can play a role in gene regulation and cancer formation to this very day. Only about 2 % of the human DNA codes for protein products [59]. This is only twice as much as in flies, worms and weeds. However, the genes are about 100-fold larger in humans, allowing complex regulation of gene expression, and with splicing, the number of coding genes is even higher [59]. The human genome contains about 40,000 HERVs today [19, 59].Fig. 6


What contemporary viruses tell us about evolution: a personal view.

Moelling K - Arch. Virol. (2013)

Endogenous retroelements (RE). (Top) A virus in a virus in a virus can be detected in cellular genes. One example is shown here with a protein kinase B inhibitor gene, which consists of up to 85 % REs [13, 59]. An integrated HERV-K(C4) is indicated. The inserts accumulate within introns, where integrations are less harmful than they would be in exons (Ex). REs comprise retroviruses and shorter versions, LINE, SINE or only LTRs [19]. (Left) The human endogenous retroviruses (HERV-K (C4)) can influence regulation of other genes, as shown for DAP3, a proapoptotic gene [13]. Antisense transcripts can shut off sense transcripts of a tumor suppressor gene and can thereby cause cancer. (Right) The number of human REs is shown as segments [modified from ref. 9]. The white area is investigated by ENCODE project
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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Fig6: Endogenous retroelements (RE). (Top) A virus in a virus in a virus can be detected in cellular genes. One example is shown here with a protein kinase B inhibitor gene, which consists of up to 85 % REs [13, 59]. An integrated HERV-K(C4) is indicated. The inserts accumulate within introns, where integrations are less harmful than they would be in exons (Ex). REs comprise retroviruses and shorter versions, LINE, SINE or only LTRs [19]. (Left) The human endogenous retroviruses (HERV-K (C4)) can influence regulation of other genes, as shown for DAP3, a proapoptotic gene [13]. Antisense transcripts can shut off sense transcripts of a tumor suppressor gene and can thereby cause cancer. (Right) The number of human REs is shown as segments [modified from ref. 9]. The white area is investigated by ENCODE project
Mentions: This was unexpected when it was discovered while sequencing the human genome [59]. On average, flies, worms and plants only contain 3-10 % transposable elements in their genomes [59]. Among the human TEs, there are about 450,000 retrovirus-like elements [59]. Infection of germline cells led to the accumulation of viral genes during evolution and made the human genome a “graveyard” of retroviral fossils. The host developed mechanisms to suppress such genes in the germline by silencing viral promoters through epigenetic modifications, e.g., DNA methylation. Mutations can likewise prevent protein expression and particle formation, yet these elements may affect host cell functions [51]. The significance of these TEs has been a fertile topic for speculation among biologists. Is it “junk DNA” [6]? Since this DNA can be transcribed into non-coding RNA (ncRNA) with gene regulatory function, it cannot simply be “junk.” The recent ENCODE (encyclopedia of DNA elements) project designated these regions as “deserts” – because of their lack of information, but important functions have now been suggested for these regions as well, especially for human diseases and gene regulation [7]. We also observed this when we studied a full-length human endogenous retrovirus HERV, which entered the human genome 35 Mio years ago, as calculated from the divergence between the two LTRs at the ends of the DNA provirus [13]. The viral promoter within the LTR is normally silenced by the antiviral response of the host cell. However, it can be activated by metabolic stress. If the activated LTR allows a transcript in the opposite direction to the transcript of a neighboring cellular gene, it is downregulated, and when it is expressed in parallel, it is upregulated. One such downregulated gene that we identified recently as a tumor suppressor gene is involved in apoptosis. LTR-driven antisense transcription resulted in prevention of apoptosis and cancer formation [13] (Fig. 6). Thus, 35-Mio-year-old endogenous HERVs can play a role in gene regulation and cancer formation to this very day. Only about 2 % of the human DNA codes for protein products [59]. This is only twice as much as in flies, worms and weeds. However, the genes are about 100-fold larger in humans, allowing complex regulation of gene expression, and with splicing, the number of coding genes is even higher [59]. The human genome contains about 40,000 HERVs today [19, 59].Fig. 6

Bottom Line: Viruses helped in building genomes and are driving evolution.Only in unbalanced situations do viruses cause infectious diseases or cancer.Are viruses our oldest ancestors?

View Article: PubMed Central - PubMed

Affiliation: Max Planck Institute for Molecular Genetics, Ihnestr 63-73, 14195, Berlin, Germany. moelling@imm.uzh.ch

ABSTRACT
Recent advances in information about viruses have revealed novel and surprising properties such as viral sequences in the genomes of various organisms, unexpected amounts of viruses and phages in the biosphere, and the existence of giant viruses mimicking bacteria. Viruses helped in building genomes and are driving evolution. Viruses and bacteria belong to the human body and our environment as a well-balanced ecosystem. Only in unbalanced situations do viruses cause infectious diseases or cancer. In this article, I speculate about the role of viruses during evolution based on knowledge of contemporary viruses. Are viruses our oldest ancestors?

Show MeSH
Related in: MedlinePlus