Giant viruses – key to viral evolution

Viruses, it is all anyone is talking about these days with the coronavirus pandemic still raging through the world and rearing it’s head in places where it was mostly forgotten such as Australia. The coronavirus is a “smaller than average” virus between 0.06 microns and 0.14 microns in diameter as determined by electron microscopy. One of my favourite aspects in virology is the difficulty in classifying viruses. However, viruses come in many sizes, shapes, and genome structures which make it exceedingly difficult for scientists to classify them. Just when scientists believe they have a classification system that is suitable, a new virus is discovered that breaks that system, like a naughty child refusing the follow the rules. Indeed, it has been proposed to place viruses in a fourth domain in the Tree of Life as a TRUC – things resisting uncomplete classification. Giant viruses are an example of this.

The first giant virus was discovered in 1992 and was initially thought to be bacteria due to its size. However, in 2003 French researchers identified the organism as a virus and name it “mimivirus” for “mimicking microbe”. Mimivirus is 400nm in diameter but contains protein filaments which extend its size to 600nm – larger than some bacteria. It’s genome is over one million base pairs long and contains over 1000 protein-coding genes, again making it more complex than some bacteria.

These features have reignited the debate as to if viruses are living or non-living. This is a complex question that incorporates chemistry, virology, and philosophy and certainly can’t be covered in this short article. But in general, prior to the discovery of giant viruses it was mostly agreed that viruses are non-living because they do not contain the machinery required for replication. Instead viruses rely on their host’s machinery for replication and thus survival. However mimiviruses do contain DNA replication proteins similar to that of bacteria and other eukaryotes.

This lead scientists Supriya Patil and Kitan Kondabagil at the Indian Institute of Technology to explore the origins of giant viruses and DNA replication. There are two hypotheses they were setting out to prove or disprove: reduction and virus-first. The reduction hypothesis is that giant viruses emerged from modern single-celled organisms that have shed genes over millennia whereas the virus-first hypothesis supposes that viruses are relics of pre-cellular life forms that gained genes over time.

Kondabagil and his team created phylogenetic trees which showed that the replication machinery in mimivirus is strongly related to that in eukaryotes. Furthermore, they used the premise that similar functioning proteins tend to coevolve together, especially those that interact with each other such as in the case of DNA replication. The team showed that the DNA replication machinery of mimivirus has coevolved over a long time scale. Finally, they found little evidence of horizontal gene transfer in the replication machinery – the act of non-sexually moving genes between different genomes in different organisms.

Evidence of horizontal gene transfer would imply mimiviruses did not initially contain replication machinery but picked up those genes over time from other eukaryotic species. It appears this is not the case, and the replication machinery in mimivirus arose early, probably from a complex ancestor. This work supports the reduction hypothesis for the origin of viruses wherein only the replication-related parts of the genome remain from their complex ancestor.

This work increases our understanding of the mechanisms viruses use to replicate and self-assemble. Understanding this process is key in modifying viral replication machinery for gene therapy or nanotechnology.

As with most things in science, looking back can help us move forward.

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