Around 33 million years ago, in the late Oligocene Epoch, a new virus emerged and infected some kinda mammal.

As we'’’re all well aware at this point, viral infections happen and spread all the time.

But this time was different.

It would turn out to be the beginning of a viral outbreak that left its mark in the genomes of almost every order of mammals around today -- the start of a huge, ancient pandemic, one that touched many different species, spanned the globe, and lasted for more than 15 million years!

Yes.

Imagine: A pandemic that lasted 15 million years.

And we know this pandemic happened because, in 2001, biologists discovered part of this ancient virus trapped in our DNA -- a molecular fossil entombed in our own genome.

This fossil was not the actual virus itself, but a fragment of its genetic material.

Scientists named this DNA sequence ERV-Fc, and it'’’s just one of a growing number of viral fossils that have been discovered in the genomes of modern animals.

And, I know you have questions about this, because I definitely do.

Like, what was this virus?

How did it end up in our genome?

What disease did it cause, if any?

And is it...doing anything in there now?

While we don'’’t have all of the answers yet, the legacy of this ancient pandemic is just one of the many stories hidden in our very own DNA, just waiting to be discovered.

Whether they'’’re animals, plants, or fungi, all living organisms have at least one thing in common: Their DNA is riddled with the remains of ancient viruses - and humans are no exception.

These viral leftovers are known as Endogenous RetroViruses, or ERVs.

And most of them are the remnants of ancient retroviruses that infected the egg or sperm cells of our mammal ancestors.

Those kinds of viruses insert themselves into their host'’’s DNA as part of their normal life cycle.

And when this happens in reproductive cells, that viral sequence can be passed down from parent to offspring.

Now, this doesn'’’t happen with every viral infection.

In fact, viruses embedding in the genome of their host is pretty rare.

Because everything has to go just right for this to happen.

First, the virus has to integrate into the DNA of sperm or egg cells at just the right spots to not kill those cells or disrupt how they work.

Then, those cells have to be the lucky few that actually end up forming a fertilized egg, which is what allows the ERV to be passed down to the next generation.

And then, it has to keep getting passed on - even as those organisms change and evolve over time.

But over millions of years, these rare events have happened often enough to leave a viral fossil record behind.

In some ways, it'’’s actually a lot like the regular kinds of fossilization that we talk about here: it requires specific conditions and only happens some of the time.

Nonetheless!, ERVs are so common in our DNA that, by most estimates, they make up around 8% of our total genome.

That'’’s about four times higher than the proportion of our genome that'’’s made up of genes - the sequences that actually code for proteins.

Yes, you heard that right, but just in case you didn'’’t get it I'’’m gonna say it again: In terms of DNA content, you'’’re about 8% virus and 1 to 2% genes.

So what I'm saying is.... You are more virus than you are genes!

Now, figuring out where each bit of that viral DNA came from isn'’’t easy.

Many of these sequences have built up so many mutations and been shuffled around so much that they'’’re really fragmented and hard to make sense of.

But in the case of ERV-Fc, that sequence tells the story of an ancient, global, multi-species pandemic.

Or, maybe more accurately, a series of epidemics, played out over a huge span of time.

And, while ERV-Fc was first identified in 2001, it wasn'’’t until 2016 that a group of biologists at Boston College was able to piece together the history of that particular ancient virus.

They searched the genomes of 50 modern species of mammals to identify fossilised sequences of ERV-Fc and found them embedded in the DNA of over half of those species.

Those sequences were even shared between species as distantly related as humans and aardvarks.

Now, when a biologist sees this kind of pattern, the first thing they try to figure out is whether there'’’s some simple evolutionary explanation for it.

Like, did the virus infect some early mammal that was the common ancestor of many different groups, so that this molecular fossil was just passed down to all of its descendants?

In this case, the answer turned out to be no - it'’’s a little more complicated than that.

Instead of one infection event, it looked like this virus independently infected different mammal species and embedded itself in their genomes multiple times.

For example, 12 of the mammals studied, including humans, pandas, and dogs, all have more than one genetically distinct sequence of ERV-Fc in their genomes.

This suggests that there were many independent infection events by different strains of the virus as it evolved while spreading around the world.

So, we actually have two different fossils of ERV-Fc in our DNA and, as far as we know, they don't do anything right now.

The older one comes from an infection in the common ancestor of all great apes, sometime between about 20 million and 16 million years ago.

And the younger one we got from the common ancestor of all African great apes, between about 16 million and 9 million years ago.

As for how widespread this pandemic was, it'’’s likely that the virus made it to every continent except Antarctica and Australia, which were geographically isolated at the time.

And this may explain why no Australian marsupials in the study, like wallabies and Tasmanian devils, were found to have any of that virus in their genomes.

So, those are some of the things that we can figure out about this ancient pandemic.

But there are other things that we just can'’’t, because the fossil record of this virus is incomplete.

After all, there are probably species that lost their sequences of ERV-Fc over time.

And others were probably infected, but the virus didn'’’t embed itself in their DNA successfully.

And some lineages that might have carried the viral fossil have just gone extinct.

So, we'’’re missing pieces of the puzzle, which makes some of the details of the viruses'’’ spread a mystery.

But, by using that method known as the molecular clock, and by building a family tree of the virus strains across mammal species, researchers think that the virus originated around 33 million years ago.

And from there, it spread around the world for at least 15 million years.

While we don'’’t know what species the virus infected first, we can tell that it started jumping from group to group pretty quickly.

There'’’s evidence of at least 26 independent transmissions between species.

And some of these events look pretty weird, because the jumps weren'’’t always between closely related species.

For example, the sequence of this virus found in dolphin DNA is closest to those found in rodents and rabbits.

Now, this doesn'’’t mean a dolphin caught the virus directly from a rabbit, or vice versa.

Although I personally would love to know what that would look like.

Like I said, the fossil record of this virus is incomplete, so we'’’re probably missing some steps there.

All we have to go on is what we know about how viruses jump between species today, like by one species preying or scavenging on another.

Beyond that, we just don'’’t know.

But one of the reasons that the virus was so successful at hopping between species may have been its ability to swap genes with other strains, and with other totally different viruses, over the course of the outbreak.

This is known as viral recombination, and it can happen when two different viruses infect the same animal at the same time.

This lets them splice elements of their genomes together as they replicate within the same cell.

And it happens naturally all the time.

In fact, it looks like this is probably what happened to allow SARS-CoV-2 - the virus that causes COVID-19 - to spread so successfully.

There'’’s good evidence that most of this virus is similar to coronaviruses seen in bats, but a bit of the protein that helps it enter its target cells looks more similar to another one found in a pangolin.

We still don'’’t know what host animal was infected by both viruses, though.

Now, recombination can also happen when a virus picks up genes from viruses that had already embedded some of their sequences in the host'’’s genome.

And researchers have found evidence of multiple recombinations over the history of ERV-Fc.

So it might'’’ve gotten the genes that helped it jump between species from other viruses and other strains.

This seems even more likely because one of those recombinations is in the protein that helped the ancient virus enter its target cells.

Which sounds...familiar.

But what kind of virus was ERV-Fc?

And how deadly was it?

Well, we do know that the virus infected mammals, replicated in their cells, and occasionally became embedded in their genomes.

And we can look at its closest living viral relatives to try to figure out what kind of infection it might have caused.

Based on its genetic structure, ERV-Fc is an ancient member of a genus called Gammaretroviruses.

Today, this group includes the Murine leukemia virus in mice and Feline leukemia virus in cats.

And one of the most common effects of this group of viruses is oncogenesis, or the formation of cancer in their hosts.

So, it'’’s possible that the ERV-Fc virus caused similar illnesses - inducing cancers.

But because we don'’’t know what kinds of cells it infected, we can't tell whether it was likely to have caused leukemias or some other kind of cancer.

And we might never know.

As the genomes of more species are sequenced, our ability to untangle the histories of these viral fossils will only improve.

Because, ERV-Fc isn'’’t the only viral fossil in our DNA.

There are mannny others in the human genome, whose stories are waiting to be told.

And without the record in our genome, we'’’d never have known this epic, ancient pandemic happened.

And these ancient remnants don'’’t just help us understand what happened in the deep past.

They show us that viruses have jumped between species for millions of years - and still do.

And they also help us understand, and predict, how new viruses behave and spread today.

Which, I think we can all agree, is pretty important.

From one mammal millions of years ago, to our DNA today, the story of ERV-Fc reminds us that pandemics are part of the history of life on our planet.

And, whether we like it or not, they'’’ll be part of our future, too.