Virological EVE: Excavating ancient viruses using paleovirology

Paleontology vs Paleovirology -what’s the difference?

A lot of people will be familiar with the term ‘paleontology’. We can study the evolution of plants, animals, and even some bacteria through the examination of their fossilised remains over millions of years, and trace their evolution through to modern-day species. However, this is not possible with viruses. Viruses are far too small to be physically preserved in rocks, as imprints, or in extreme preservation conditions such as peat bogs.

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It’s not possible to find physical traces of viruses in the fossil record, so science has turned to genetics for answers…Photo by Pixabay on Pexels.com

 

How can we determine viral evolution?

It’s possible to observe viral evolution over the course of a short period of time. In my last article, I mentioned how HIV vaccines have trouble keeping up-to-pace with the constant mutation and evolution of the virus within the host- this is an example of rapid evolution of a single virus strain. However, it does not give us much insight into the overall existence of a viral species, how long it has existed for, and what animals it infects.

Palaeovirology is a new area of research, made possible by the ability to sequence whole genomes and study them in-depth. All viruses require a host cell to replicate, and many do so within the nucleus. Some viruses, known as retroviruses, are known to integrate into the host’s genome as part of their replication lifecycle. I’ve previously written a post on an endogenous retroviral gene, syncytin, that may  have a function in humans. This is a neat example of how a viral gene has incorporated itself into the mammalian genome, and has been utilised by the host.

However, it is possible for genes that do not belong to retroviruses to transposed into the host’s genome by accident. They become EVEs (endogenous viral elements), and under the right integration conditions, can be passed from the host to its offspring, and from offspring to fixation within a population. This leaves a ‘fossil’ of the virus within the genome of a species. Through genome sequencing and alignment with known virus genomes, it is possible to find hundreds of EVEs spread across the animal kingdom. If more than one species of animal shares an EVE, we can determine that the virus is at least as old as the last common ancestor of these animals, and sometimes millions of years older than originally thought.

 

The EVE-ntual success – Paleovirology as a game of chance

It’s worth spending a moment to consider how amazing it is that paleovirology exists.

Firstly, it is incredibly unlikely that a virus, upon replicating within a host’s nucleus, is able to integrate all or part of it’s genome into the host’s genome. For this to occur in a germ-line cell, that eventually is the one out of millions to form offspring, has a probability that’d be too small to fit on one line of this page. After this, for the EVE to reach stabilising selection within a population, where it is fixed within the genome of the species, is so infinitely unlikely that it’s a wonder that there are any detectable EVEs at all.

So it’s rather cool that through deep genome sequencing, we are able to find these ancient viral traces, and use them to learn more about viral evolution!

 

Original EVEs

The discovery of EVEs in animal genomes means we can trace the age of a genus or family of viruses, and from this infer their co-evolution alongside a species. For example, identical EVEs discovered in mice and rats show that the same Filovirus (the family of viruses that include Ebolavirus), has been co-existing with these rodents for over 30 million years. EVEs have been found all across the animal kingdom, from bats, dogs, and dolphins, to zebrafinches, possums, and koalas! From the deep sequencing of genomes, it transpires that 8% of the human genome originates not from mammals, but from endogenously-inserted viruses.

 

Useful EVEs

There has been debate over the presence of these viral sequences in mammalian genomes. Evolution dictates that, if a gene does not have a functional use within the host, genetic drift over millennia will cause random mutations to arise, which are not selected out of the population. However, several EVEs show positive selection; that is, they do not contain the random mutations that are expected if they are non-functional or harmful to the host.

One example is the Bornaviruses, which can infect a wide range of mammals. Following a broad search of genomes, Horie et al repeatedly discovered EBLNs (endogenous Borna-like N elements), which bear distinct similarity to the Bornavirus nucleoprotein gene, spread across the mammalian phylogeny. The earliest of these EVEs was introduced into the genome more than 50 million years ago, providing evidence that Bornaviruses and mammals have co-existed for a very long time. These EBLNs are transcribed to produce mRNA, the precursor of proteins, and alongside their conserved sequence, suggests that they have a currently unknown function within their new genetic hosts.

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The Koala genome has traces of EVEs from Koala retrovirus (KoRV)

 


The papers:

Katzourakis and Gifford. Endogenous viral elements in animal genomes. PLoS Pathogens. 2010.

Tarlington, Meers, and Young. Endogenous retroviruses. Cellular and Molecular Life Sciences. 2008.

Horie et al. Endogenous non-retroviral RNA virus elements in mammalian genomes. Nature. 2010.

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