I am virus – animal genomes contain more fossil viruses than ever expected

EbolaIf you think about fossils, you probably picture a piece of bone or shell, turned to stone and buried in the ground. You visit them in museums; some of you may even have found some. But your closest fossils are inside you, scattered throughout your genome. They are the remains of ancient viruses, which shoved their genes among those of our ancestors. There they remained, turning into genetic fossils that still lurk in our genomes to this day.

We’ve known about our viral ancestors for 40 years, but a new study shows that their genetic infiltration was far more extensive than anyone had realised. The viral roots of our family tree have just become a lot bigger.

When viral genes were first found among animal genomes in the 1970s, all of them came from the retroviruses, a group that includes HIV. As part of their life cycle, these viruses smuggle themselves into the genomes of the cells they infect, making new copies of themselves using their host’s own machinery. These copies usually cut themselves back out to form new virus particles but sometimes, they stayed behind. Some were passed down through the generations and became permanent parts of their host’s genome. Today, these “endogenous retroviruses“, or ERVs, make up around 8% of all our DNA.

But the retroviruses weren’t alone. Scientists have recently discovered that other viral dynasties have also become genomic trespassers. In 2009, French scientists found that some wasps have accosted the DNA of polydnaviruses for use as biological weapons. In January this year, a Japanese team announced that another family – the bornaviruses – have penetrated the genomes of animals, including humans. In the summer, American teams showed that the same was true for filoviruses, such as the lethal Ebola and Marburg. Just last month, fragments of hepatitis-like viruses were found hiding out in the genes of the zebra finch.

Now it seems that even these discoveries were just the tip of the iceberg. Aris Katzourakis and Robert Gifford have found that the animal kingdom is rife with viral genes. By screening the entire genomes of 44 species, they found fossils representing ten other families beyond the retroviruses. Some of these ancient viruses are relatives of today’s most infamous varieties: influenza, Ebola, hepatitis B, rabies, dengue and yellow fevers, and more. The term ERV is clearly too narrow, so Katzourakis and Gifford describes these genetic fossils by the more inclusive name of “endogenous viral elements” or EVEs.

Most of them are broken and fragmented. Riddled with crippling mutations, they are like books whose pages have been smudged, torn out and written over. But not all – some seem intact, and their information can still be read today. One of these, known as EBLN-1, is found in humans and other primates. It came from an ancient bornavirus and its slow pace of evolution means that we’ve probably co-opted it into our own genomes, recruiting it into an active role.

It’s not clear what that role might be, but Katzourakis and Gifford think that it might help to protect us against its own kind. Other groups have suggested that this is a common theme – the fossil viruses become recruited as sentinels that fights off invasions by their live cousins. If that’s the case, you’d expect the live viruses to eventually evolve countermeasures. When this happens, the EVEs become useless, the benefits of keeping them intact dwindle, and mutations start to build up. And that’s exactly what you see with EBLN-1 – in animals like orang-utans and marmosets, it has started to lose its integrity.

While a minority of EVEs have an active physical role, the sequences as a whole have much to tell us about the evolution of viruses themselves. EVEs are windows into the past, just as all fossils are. As an example, step away from viruses for a minute and consider whales. it’s difficult to imagine how whales evolved from land-based ancestors by comparing modern species, all of which share the same set of advanced sea-going adaptations. However, a stunning series of fossil whales makes the gradual transition from land to sea that much clearer.

It’s even more difficult to understand the history of viruses by looking at modern ones, because they evolve at a lightning pace, switching hosts, shuffling genes and even losing entire lineages. The EVEs provide a glimpse into these lost events, telling us how old viruses are, which hosts they used to infect, and even how they were transmitted.

When EVEs were first introduced into an animal’s genome, they became dragged along for the ride as that species evolved. Today, the host’s descendants all carry similar EVEs. Those similarities provide an important historical clue – they tell us that the last common ancestor of species with related EVEs must have had the viral DNA in its genome. By working out when that ancestor was around, we can work out how old the group of viruses are. With enough data, you could even piece together the genomes of the ancient viruses themselves. As a commenter said, the last time I wrote about this, “Then we can say want kind of genome the flu had which infected T. rex. That would be totally awesome.”

Take the bornaviruses. When they were found in animal genomes earlier this year, it was clear that those in our genome had been hitching a ride in animal bodies for 40 million years. But Katzourakis and Gifford’s study shows that this group is much older than that. Based on closely related EVEs from elephants and tenrecs (a hedgehog-like creature), bornaviruses have been around when the last common ancestor of elephants and tenrecs were – and that’s at least 93 million years ago.

EVEs can also tell us about the hosts of ancient viruses. Today, filoviruses like Ebola are thought to infect bats and primates. Last year, one strain was discovered in Philippine pigs. But the tell-tale EVEs show that these viruses also used to infect insect-eaters like shrews, rodents like mice and rats, and marsupials like wallabies and opossums. They certainly used to have catholic tastes in hosts, and they still might do. In this way, EVEs could tell us about modern animals that could act as reservoirs for notable deadly viruses.

They can also tell us about viruses that jumped from one animal to another. Katzourakis and Gifford found an EVE in the genome of the bottlenose dolphin that seems to be very closely related to dependoviruses that infect birds, like chickens and ducks. This doesn’t mean that a duck infected a dolphin; remember that EVEs are fossils of infections that plagued the distant ancestors of current species. However, it does strongly suggest that in prehistoric times, one such virus jumped from birds to mammals, as often happens today.

Reference: PLoS Genetics http://dx.doi.org/10.1371/journal.pgen.1001191

Update: More unabashed joy at this discovery from Carl Zimmer. Look out for his upcoming book on viruses.

Image by Thomas Geisbert

More on fossil viruses:

If the citation link isn’t working, read why here

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There are 6 Comments. Add Yours.

  1. TR Gregory
    November 18, 2010

    You forgot to say “They may not be junk after all as was long assumed”. :-)

  2. Daniel J. Andrews
    November 18, 2010

    Am I missing something, Ed? The Carl Zimmer links takes me to your (this) page.

    Edit: Ok, got it. I think you probably wanted this link.

  3. Tk
    November 19, 2010

    This is interesting, but I’m puzzled about one thing. I presume that EVEs can be passed on to offspring only if the original virus infected the gonads. Is that true of the viral fossils? Somehow I was under the impression that viruses tend to target only certain kinds of cells. (For instance, is it true that HIV attacks only the immune system?) If instead they infiltrate all sorts of cells, why don’t viral infections cause symptoms all over the body? I guess I just don’t understand how viruses work — and ditto about horizontal gene transfer.

  4. Lije
    November 19, 2010

    The link for “this is a common theme” seems to be broken. Takes me to this blog with a 404.

  5. amphiox
    November 22, 2010

    (For instance, is it true that HIV attacks only the immune system?)

    No. It can infect other cell types, including neurons.

  6. Chris Carter
    November 29, 2010

    Viral DNA has also infiltrated the human genome: Taking a different approach than the Katzourakis and Gifford paper, translated viral genomes (herpes simplex and other herpes viruses, influenza and the common cold virus, and many others) were compared to the human proteome by BLAST analysis. Thousands of short contiguous pentapeptide sequences , and sometimes greater are littered throughout the human proteome, and in fact the human genome appears to be composed almost entirely of viral DNA. This evidently has important implications for evolution.
    The protein homology is also critical to our understanding of disease: Current viruses express proteins that are similar to our own, and upon infection will be able to act as dummy ligands, decoy receptors or enzymes, and will also interfere with protein/protein interaction networks. Such homologous viral inserts are likely to play a key role in a multitude of human diseases.

    The BLAST analyses, representing over a million such alignments, can be viewed at http://www.polygenicpathways.co.uk/BLASTS.htm

    and some of the consequences are discussed in a series of prepublications at NaturePrecedings


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