Our Inner Viruses: Forty Million Years In the Making

Each year, billions of people get infected with viruses–with common ones like influenza and cold viruses, and rarer ones like polio and Ebola. The viruses don’t stay all that long inside of us. In most cases, our immune systems wipe them out, except for a few refugees that manage to escape to a new host and keep their species alive. In some cases, the viruses kill their unfortunate hosts, and end their own existence as well. But in some exquisitely rare cases, viruses meld with the genome of their hosts and become part of the genetic legacy their hosts pass down to future generations.

Scientists know this melding has happened because viruses have distinctive genes. When scientists scan the human genome, they sometimes come across a stretch of DNA that bears the hallmarks of viruses. The easiest type of virus to recognize are retroviruses, a group that includes HIV. Retroviruses make copies of themselves by infecting cells and then using an enzyme to insert their genes into their host cell’s DNA. The cell then reads the inserted DNA and makes new molecules that assemble into new viruses.

Most of the time, retroviruses behave like other viruses, jumping from host to host. But sometimes a retrovirus will end up in the genome of an egg or sperm. If it then ends up in a new embryo, the embryo will carry a copy of the virus in every single cell–including its own egg or sperm. And on and on, from parents to children to grandchildren.

If the virus DNA remains intact, it still has the capacity to multiply. It may produce new viruses that break out of a cell, and even leap into a new host. But over the generations, the virus DNA may mutate and degrade. It may no longer be able to escape its own cell. But the virus may still have a bit of life left to it: it can make new viruses that insert their genes back into the genome at a new location. Here’s a simplified diagram of how it works…

Dewannieux and Heidmann 2013 dx.doi.org/10.1016/j.coviro.2013.08.005
Dewannieux and Heidmann 2013 dx.doi.org/10.1016/j.coviro.2013.08.005

This process has generated a huge amount of viral DNA in the human genome. We carry about 100,000 pieces of DNA that came from retroviruses–known as endogenous retroviruses. All told, they come to an estimated 5 to 8 percent of the entire human genome. That’s several times more DNA that makes up all 20,000 of our protein-coding genes.

When biologists started sequencing the genomes of other species, they discovered that it’s taken millions of years to pile up all this viral DNA. They found some of the same endogenous retroviruses in the genome of chimpanzees, for example. Since our ancestors split from theirs about seven million years ago, this shared viral DNA must come from our common ancestor.

Gkikas Magiorkinis, a University of Oxford virologist, and his colleagues have now carried out large-scale survey of endogenous retroviruses in humans, apes, and Old World monkeys–a group of species that all descend from a common primate ancestor that lived some 40 million years ago. They catalogued the viruses in each species and compared them to the versions in the other primates. They were able to reconstruct the history of our viral DNA in unprecedented detail, even coming up with estimates for the rate at which the viruses inserted new copies into our genome.

The scientists can trace our viral DNA to 30 to 35 separate invasions. Once each virus established itself in our ancestors’ DNA, it produced copies of itself scattered through the genome. The rate at which new copies were inserted rose and fell over time, and at different rates in different branches of the primate tree. Here’s an overall look at the history of the viruses. (“Loci” here refers to new copies of viruses inserted into the genome in a given interval of time.)

Magiorkinis et al, Retrovirology 2015
Magiorkinis et al, Retrovirology 2015

Our monkey-like ancestors 40 million years ago acquired new virus copies at a fast clip–much faster than in our own lineage in the past couple million years. One virus in particular, known as HERV-H, was responsible for most of the new copies. It may have evolved adaptations that made it into a superspreader inside the genome.

In the Old World monkeys–represented in the new study by baboons and macaques–the rate of new virus copies pretty much stayed the same over the past 30 million years. But the apes tell a different story. The rate dropped in every ape branch. The same shift occurred in parallel in the ancestors of humans, chimpanzees, gorillas, orangutans, and gibbons.

It’s possible that some of this decline had something to do with the fact that we have been fighting back against our inner viruses for millions of years. A newly inserted virus may disrupt an essential gene, and the result may be that its cell may become cancerous. Scientists have documented this threat by studying mice, which are often the victims of retrovirus-driven cancer. And they’ve also found that mammal cells can minimize this risk in many ways. One way is to coil up virus DNA so that it can’t get copied. Another way is to make special proteins that damage newly made virus genes.

One thing that apes have in common is that they’re big. If you’re a big animal, that means you have more cells, and more cells should mean you have a bigger risk of developing cancer. Yet we don’t. The risk of cancer in a human is no greater than a mouse. It’s possible that an increase in body size drives the evolution of new defenses against cancer. And those defenses may include doing a better job of keeping viruses in check.

But Magiorkinis and his colleagues suspect that getting big can only explain some of the decline. In the human lineage in particular, viruses have slowed down drastically. Here’s a graph from their new study that tracks the frequency of new virus copies in the human genome over time:

Magiorkinis et al, Retrovirology 2015
Magiorkinis et al, Retrovirology 2015

In the past million years, only a single virus has continued to multiply–known as HERV-K. Today, you can find some HERV-K copies in some people and not in others. The pattern of these copies suggests that as recently as 250,000 years ago, HERV-K was still making new copies.

It’s possible that HERV-K is completely dead now. There’s no evidence that HERV-K or any other endogenous retrovirus is actively spreading or causing cancer. It’s hard to say at this point why humans have put the brakes on endogenous retroviruses. But Magiorkinis has one suggestion: our ancestors may have reduced their odds of picking up new viruses.

Retroviruses like HIV can be spread by blood. Other primates use their teeth as weapon, either to kill prey or to fight other primates. If their victim has an infection, they can get infected, too. Ancient humans evolved to gather food with tools rather than teeth. Males stopped chomping other males, a shift that is reflected in the shrinking canine teeth of our ancestors. By making ourselves less vulnerable to blood-borne viruses, we put a stop to the influx of retroviruses overrunning our genomes.

There’s no way of telling if we are done with new endogenous retroviruses for good now, or if HIV or some other new retrovirus will manage to work its way into our genes. But the history of our inner viruses is still important to our health. Scientists have found HERV-K proteins made in tumors, suggesting that cancer cells may harness some of the biochemical power in these ancient parasites. Knowing their past can let us understand how they’ll affect us in the future.

(For more information, see my book A Planet of Viruses.)

Reference: Magiorkinis et al, “The decline of human endogenous retroviruses: extinction and survival.” Retrovirology.

27 thoughts on “Our Inner Viruses: Forty Million Years In the Making

  1. It would be interesting if the missing link between humans and other primates was found through viruses buried in our DNA instead of through a fossil record.

  2. All things were created by God. But only man was made in the image of God. The use of the word “ancestors” in relation to man and apes, is such an empty excuse for finding meaning to our human lives. Biologically, we might have things similar to apes, but by no means does that imply that we “came from apes”. The sun, moon, earth, animals, and man, all have the same source – that they were all created by God (Gen. 1:9-27). But only MAN was made in the image of God (Gen. 1:26). In Gen. 2:20, we see that God brought every animal to Adam, the first man created, “to see what he would call them” (Gen. 2:19), but we see that “…for Adam there was not found a helper as his counterpart.”. All the birds, cattle, and every animal of the field, even in the very beginning of time, man realized did not complement him, did not match him. He was unique. He was made in the image of God and after His likeness. We are made in the image of God, after His likeness. We did not “descend” from some apes and monkeys millions, or thousands of years ago.

  3. Viral DNA or RNA that benignly settles itself into a vector or inside human DNA itself turns into a sleeping gene, enjoying the protection of a longer-lived cell. That means it doesn’t aggravate the immune system to destroy it. That could easily account for the tolerance of humans and new world monkeys to all the viral DNA that has accumulated all this time. Social patterns can only account for so much, since many viruses travel through touch and aerosol to infect others. Blood is not the only means of transmission.

    Evolution in small organisms proceeds at a much more rapid pace than in organisms even as small as a shrimp. This is because generations recur in very short periods of time: one virus invades another cell, produces progeny, they break out of the cell and do the same–and there are many cells they can invade. The more generations there are–and you get many in one bout of illness–the more chance there is that a quiescent mutation can occur. This mutated virus can invade a cell and just lie low. It has the opportunity to replicate any time a cell divides, such as when new skin is grown, new organ cells are generated, and new stem cells are generated.

    Once a virus lies dormant in a cell, it stops reproducing by commandeering the cell and filling it with viruses which rupture the cell. Replication of cells in the host is much slower, and the virus does not cause illness or death. This is the mark of a successful parasite.

    In cases where a virus lies dormant but the cell begins to die, the virus often “jumps ship” and creates more copies of its virus and again infects the body. It can do this more easily when the body’s immune system has declined.

    But our societies have learned how to prevent spread of viruses and take action to prevent this spread. And so the successful viruses–those that lie dormant in our genes–reproduce more slowly, at the pace of human cell replication.

    Evolution is a funny thing, though. Over time, changes in DNA can cause dysfunctions of genes through bad replication fidelity, and these quiescent viruses are subject to this, too. Do this a lot, and over hundreds of thousands of millennia these viruses lose their ability to replicate effective viruses. This is called attenuation.

    Doctors also use lab-created attenuated viruses to produce vaccines. Such vaccines have the virus’ protein coat which will cause a reaction in the person’s immune system, but the DNA inside has been deactivated, so an infection cannot occur. This produces a stronger immune protection to build than is caused by a heat-killed virus (the more common form of vaccine).

    Attenuation over hundreds of millions of years can easily be time enough to reduce the ability of a virus to continue its viral replication.

    But what I want to know is if 5% of human DNA is viral and “unconnected” to effective human DNA, what is it doing there? Is it what has, in the past, been called “junk DNA?” Does it provide an explanation of what was once called “jumping genes?”

    That “extra” DNA must be there for some purpose. I’d like to see it studied to see if it has something to do with the creation of our immune system or if it has a use by itself, such as the creation or modification of different kinds of RNA such as messenger RNA (mRNA) and transfer RNA (tRNA).

    If such viral DNA is responsible for cancers, then can it be a mechanism by which the body deals with the cancer? Is it a tool that researchers can use to create immunities against and/or treatments for cancer?

  4. B.B. and “The Truth” may want to stop reading articles that vet them so riled up. Maybe God’s creation of us was a series of steps that took tens of millions of years. To God that may be just a small moment in time. Your beliefs are just a different angle of the same thing. Science is the steps of the recipe and Religion (all of them) is the beautiful cake all decorated and ready to admire. It is, after all, the 21st century and our brains were also made in God’s image. We are supposed to be learning and evolving in our understanding of our existence past and present.

    Great article and comments. Understanding microscopic organiorganisms and how we relate to them can teach us a lot about our species and how every species exists in a world we are still trying to navigate.

  5. Splendid discoveries. I always thought the smaller organisms had an advantage over bigger animals in the evolution because they reproduce more plentifully and they have evolve much earlier in life. Good to know more about this.

  6. It’s ironic that this column attracts attacks from the Creationists, since it doesn’t explicitly point out that the virus study referred to offers support, completely independent from other lines of evidence like morphology, for our shared ancestry with other primates, and indeed provides a road map for when we diverged from various groups. Why else would we share the exact same endoviruses with apes, if not from a common ancestor?

  7. @The Truth : Man was not created by God, the story of Adam and Eve was written to teach us all a lesson and all of the objects seen in this story represent something.

  8. Hey Creationists! If you don’t want to come along with the rest of the modern world, and instead cling dearly to your time worn mythologies, you certainly have that right. But squealing about the science is not going to make it all go away.

    Perhaps you can try sticking your fingers in your ears and saying “la la la la la la la la la” instead of attacking that which you clearly do not understand or would refuse to admit to, if you did.

  9. Very interesting. Although not explicitly shown in this posting, there are many virus insertions (and transposable element insertions) in our DNA that are at the exact same positions in chimpanzees. That cannot be a coincidence. It is like ‘DNA fingerprinting’ evidence of our common ancestry with another species.
    Of course the detail that needs to be pointed out is that these insertions become ‘fixed’ into all individuals of a population by a long history of genetic drift.

  10. I think The Truth and Gts should watch this. God obviously doesn’t care about his own image.


    If you have religious comments post them on a religious forum to people who care. This is a science article and should be commented on the science community or peopple who want to learn.

    Very interesting article. Its amazing how the human body hasn’t been able to notice the added DNA and destroy it even work on a way to capture and purge viruses within the body if viruses too came from a common ancestor.

  11. So, the Earth was “invaded” by viruses and evolution started… then we conceived God, who has now been superceded by capitalism!

  12. I wonder if our species has since become dependent on the modified DNA? What would happen, theoretically, if we were to remove it? More interesting still, could the ancient retro-viruses have had a hand in the evolution of our species? Are there branch offs that died out due to any of these and yet somehow we were able to adapt and overcome? Great article!

  13. Hey, I’m not a creationist but I wanted to advance a creationist theory: viruses and retroviruses were created to be part of a helpful ecosystem, retroviruses’ ability to shelter in the genome was created to avoid degrading effects in cytoplasm. speculative source So I guess the theory is that similar organisms had similar viruses that hid in exactly the same spots since they were designed perfectly. Even if it’s a stretch, I prefer creationists with working theories to the kind who showed up here, and didn’t want it to seem like the fanatics were the only face of creationism.

  14. Evolution is not a theory, IT IS THE WAY life works. Like gravity… it is not a theory… it is the way things work. That is fact… despite whatever a bunch of ignorent people say. So fact remains… and Creationism is out of the window.

  15. According to proponents of Charles Darwin, the selection is organismal.In other words, the entire organism is selected/unselected depending upon what types of variations are there.The selection pressure falls into the genome and ultimately on genes of the genome. These inducted viral genes may act as cushion for those genes that stand the risk of elimination. Do these retrovial elements then help in speciation?

  16. Integration of viruses in human genome and its ancestors is fairly understandable because of the equipments viruses are possessed with.
    These viruses once integrated have changed their position in the genome briskly and have affected the expression of genes. They too have undergone mutations fairly rapidly making them attenuated or neutralized. As far as natural selection is concerned they offered umbrella to vital genes thus protecting them from the intense natural pressure. Viral genomes by their presence seem to have added to the fitness to a particular environment, and added plasticity to the genome, and enabled speciation.

  17. I just want to support Jamie and others who have commented on creationist’s unnecessary intrusions into these informative scientific sites. If creationist’s don’t accept evolutionary theory then don’t infest evolutionary sites. I don’t comment on creationist sites, at least give me the same courtesy. Stay away.

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