Virophages and the evolution of transposable elements

Fischer, M., & Suttle, C. (2011). A Virophage at the Origin of Large DNA Transposons Science, 332 (6026), 231-234 DOI: 10.1126/science.1199412

This paper reports the discovery and characterisation of a virophage, Mavirus, and postulates that it’s similarities with a family of transposable elements suggest a common evolutionary origin.

Mavirus (white arrows) in the virion factory of CroV (CroV viral particles white arrow head, black arrow - a potentially defective CroV capsid)

Mavirus is the second virophage so far discovered. Both it and the other, Sputnik, parasitize giant viruses that infect protists. There is some controversy as to whether these viruses should be classified as virophages or a new class of satellite viruses. Virophages are predicted to have no nuclear phase in their infection cycle, to replicate in the virion factory of the host virus and to be dependent on enzymes provided by the host virus rather than the host cell. Mavirus is associated with the Cafeteria roenbergensis virus (CroV) that infects the marine phagotrophic flagellate C. roenbergensis. Mavirus can’t replicate in the absence of CroV, and CroV production and host cell lysis was reduced when infected with Mavirus.

The Mavirus has a 19kb circular double stranded DNA genome that is predicted to contain 20 protein coding genes (fig 1).  Between each gene the researchers found promoters that are highly similar to the predicted late promoter motif in CroV, implying that Mavirus gene expression is activated by the transcription machinery of CroV. Only four Mavirus genes showed homology with those on Sputnik, the other known virophage (including those encoding the capsid protein and a DNA pumping ATPase).

Figure 1. Genome diagram of Mavirus. Genes conserved with MP TEs are in red. Genes sometimes found in MP TEs in blue.

More genetic homology is found between Mavirus and a class of DNA transposons: the self-synthesising Maverick or Polinton Transposable elements (MP TEs). MP TEs are between 9 and 22kb long and encode up to 20 proteins. A conserved subset of genes is found in all MP TEs including a retroviral integrase (rve-INT) (responsible for DNA integration), a protein primed DNA polymerase B (PolB), an ATPase similar to those responsible for packaging dsDNA in viruses, and a cysteine protease with adenoviral homologues. Genes for all four of these proteins were found in Mavirus as well as another three often encountered in MP TEs.

The best evidence for a close evolutionary relationship between Mavirus and MP TEs was the identification of a region of synteny between Mavirus and a genomic fragment from the slime mold Polysphondylium pallidum that contains a MP TE-like fragment (fig 2).

Fig 2. Comparison of gene organisation between Mavirus and a truncated MP TE from P. pallidum. homologous genes are the same colour and the syntenic region shown in green.

Another resemblance between MP TEs and Mavirus relates to genome structure. MP TEs have terminal inverted repeats of several hundred nucleotides, and highly conserved ends starting with 5′-AG and ending with CT-3′. Although the Mavirus genome is a circular molecule at one point it encodes a ~50bp inverted repeat with the potential to adopt a hairpin structure. The adenine at the top of this hairpin was designated position 1 of the genome. Cutting the Mavirus genome between nucleotides 19,063 and 1 would result in the same termini as MP TEs and inverted repeats.

All these parallels between MP TEs and Mavirus suggest that the two are derived from a common ancestor. The question is whether the common ancestor was a transposable element or a virophage? The authors consider that the more parsimonious explanation is that a Mavirus ancestor (MVA) gave rise to MP TEs, and go on to suggest a possible evolutionary scenario. In early eukaryotic cells susceptible to infection by large DNA viruses there would be selective pressure on the host cells to stabilise relationships with a MVA. The acquisition of a retroviral integrase gene by MVA and integration in the host cell genome could have conferred protection against the large DNA virus. Various endogenisation of virophage events would create provirophages that may have led to various MP TEs. The close relationship between retroviruses and retrotransposons has long been known. This characterisation of the links between a DNA virus and a class of DNA transposable element yields similar insight into the evolution of mobile DNA and it’s importance in genomic evolution.


One response to “Virophages and the evolution of transposable elements

  1. Hi there, great post! Have you considered submitting it to the next Molecular Biology Carnival? I’ll be hosting it, and you can find all the info here. Thanks!

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