Viruses Have Always Been With Us

Some researchers argue that viruses form their own kingdom of life, and originated prior to the last common cellular ancestor.

Viruses are all about, even more of them than bacteria. The pandemic has focused our attention on one of them, but they are truly astronomical in diversity and numbers. Where did they come from? This has historically been thought a pointless question, since, even if one concedes that they are life forms of a sort, they mutate and evolve quite a bit faster than cells and organisms do, erasing most of their history. Additionally, they have been thought to exchange genes at a high rate with their hosts, also tending to erase whatever history they retain. But an article published back in 2015 fought back against all this pessimism, and made the case that virus histories can be reconstructed on a global scale and have some very interesting things to tell us.

Their first point is that gene exchange between viruses and hosts is less confusing than thought. Cells certainly have adopted viral genes at a high rate. Our own genomes are chock full of retroviral remnants, for instance. But functional genes are a different story. Relatively few seem to have gone either way (though see Koonin et al., arguing that many viral capsid and coat proteins were adopted from cellular genomes). The core viral replication proteins, such as the SARS-CoV2 RNA polymerase, for instance, is not related to cellular enzymes, and seems to be very ancient. The authors suggest that such key components originated even before the last common cellular ancestor- the point of divergence between archaea, bacteria, and eukaryotes.

To overcome the main technical hurdle of rapid evolution, the authors use protein fold analysis. Instead of studying DNA sequences, (which evolve quite rapidly), or protein sequences, (which evolve more slowly), this uses the shape of the protein, which tends to persist even after sequence similarity is completely lost. This is one way to get at very deep phylogenies, and they claim that it points to a substantial set of protein folds that are specific to viruses and wide-spread within viral families. They point out additionally that these proteins tend also to be confined to families of viruses, one more indication that virus evolution has not been promiscuous, but rather remarkably traceable through time. Viruses are classified into major families by their mode of replication. Thus RNA viruses and DNA viruses appear to have, for instance, distinct and ancient lineages.

One way to make sense of these observations and claims is that viruses were actually cells at very early times. It is common for parasites to progressively lose functions that are needed in the free-living state but become unnecessary when living off one's parents, er some other fully competent cell. The closer the symbiotic or parasitic association, the fewer functions the parasite needs. If the parasite is intracellular, then a huge amount of cellular overhead can be dispensed with. Mitochondria evolved this way, from free-living bacteria to organelles now with only about 33 genes. 

Viruses come in all sorts of sizes, from nearly cell size, encoding a thousand genes, down to specks of RNA only 250 nucleotides long. This diversity suggests the plausibility of their origination as cells, and subsequent down-scaling through a parasitic lifestyle.

But what were those cells, and whom did they parasitize? The distinct and peculiar gene complements and mechanisms of viruses, particularly the RNA viruses, suggests that they originated prior to the major split of existing cellular kingdoms. It stands to reason that cellular life has been saddled with parasites and viruses almost since the advent of cells, so some of these virus families may predate the advent of DNA, thus the prevalence of RNA viruses. The authors do an analysis of ages of the protein folds they find and their distribution, and suggest that those folds shared in all domains of life (viruses, archaea, bacteria, and eukaryotes) show that those from this set found in RNA viruses are significantly older than those found in DNA viruses. Such protein folds that are universal would be the most ancient, so finding differention among which viruses have them suggests that the major virus lineages come from different epochs of this most ancient era of cellular evolution. Interestingly, the pattern they do not find is one reflecting the cellular domains of life, which would be the case if viruses arise continuously or in relatively modern times from their cellular milieu.

Phylogenetic tree of protein folds from all domains of life, including viruses. Note the close clustering of RNA viruses near the root, and the early distribution of other viruses, compared to the later divergence of cellular domains. This kind of stretched phylogenetic tree is unfortunately symptomatic of an unsually high evolutionary rate, which is also a viral property. So it is not clear whether these authors have fully resolved this issue with their protein fold-based methods.

 

The upshot is that these authors promote the idea that viruses should constitute their own superkingdom of life, in parallel with the major cellular superkingdoms- archaea, bacteria, and eukaryotes. The rooting/ordering of the cellular tree remains quite controversial, but viruses are clearly something else again. They exchange a fair amount of genetic material with cells, but retain noticeable traces of early protein and RNA evolution. The idea that they arose from primitive or proto-cells also makes sense as a general proposition, for otherwise it is difficult to imagine their origin, such as from naked nucleic acids. This whole view remains quite controversial in the field, however, given the difficulties of the molecular analysis and the general prejudice against viruses as proper forms of life. But I think time will bear out this view and add a significant feature to early, as well as current, evolution.

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