Silent Viruses Awaken Briefly in Early Human Embryos
These Old Viruses May Help Protect Against New Viral Attacks
Like zombies rising from their graves, "dead" viruses rise up from our DNA early in development. (Wikimedia Commons)
October 21, 2015
Human DNA is a graveyard of over 100,000 old, (mostly) dead viruses. These remnants of viral attacks that happened over millions of years may make up to 8% of human DNA. It is a very crowded graveyard.
New research led by Prof. Joanna Wysocka with collaborative help from CEGS scientists at Stanford University suggests that some of these viruses may, like the zombies in Michael Jackson’s Thriller video, occasionally come back to life for a brief moment. And unlike those zombies, these viruses may be doing us all some good. They may also help us to be who we are.
The research by Grow and colleagues shows that very early on in development, before an embryo has even attached, some of these viruses spring to life. Then, after a short time, they return back to their grave.
Much More Useful Than Zombies
These researchers found that cells with resuscitated viruses were better able to fight off attacks from similar, outside viruses. Perhaps early embryos turn these viruses back on to keep new ones from invading. Our DNA is crowded enough already, thank you very much!
At this point this is just a theory but it is a good one. More research will be needed to pin it down.
Grow and coworkers also found that these live viruses affected how cells used some of their own genes. It may be that this viral tweaking of genes helps to make us human.
The idea is that humans and our closest relative, the chimpanzee, have pretty similar genes but a different set of viruses. Human viruses might cause us to use our genes differently than a chimpanzee ends up using its genes. Genes + Viruses = Human.
Of course there is more to being a human than the old viruses littering our DNA. But those viruses may be part of the answer.
And your viruses may also help to make you different from me. This is because there are small differences between people’s viruses. So your viruses may tweak your genes in a subtly different way than do mine resulting in slight differences between us.
As you can tell, there is still a lot of research to be done on why these viruses are springing to life. But the same is not true for the how. This study has done a pretty good job at figuring out how a few viruses can come to life for one brief moment at the beginning of human life.
Most of the dead viruses in human DNA are really dead. They have been so battered by mutation that the bit that is left could never spring back to life.
The exception to this is the most recent invader, HERVK(HML-2). These viruses entered our DNA as “recently” as a couple of hundred thousand years ago. Yes that counts as recent for this kind of virus.
Like the zombies in Thriller, these viruses are intact enough to still function. But they are not reanimated by an infectious beat. Instead, they come to life because of a couple of things that happen early in development.
The first has to do with an important player in the early cell, Oct4. It is present in an egg and there is even more of it once the embryo gets to the 8 cell stage.
Oct4 is a transcription factor whose job is to turn on certain genes in the cell. And it turns out it doesn’t just turn on genes either. It can also reanimate the newest viruses on the block, HERVK(HML-2).
But Oct4 can’t bring other, older viruses back to life. This is even though all of the viruses in human DNA are pretty similar.
To understand why Oct4 can only turn on a few of the viruses, we need to go into a bit of detail about how genes are turned on. And how transcription factors work.
Finding the Right DNA
As I said earlier, Oct4 can turn on some genes. What is implied in that is that it can also NOT turn on other genes. In other words, it has to be able to discriminate between genes it should turn on and ones it should ignore.
It can tell which genes to turn on by the DNA near those genes. Genes turned on by Oct4 have certain addresses that it can recognize.
Now of course they aren’t really addresses. Instead they are certain DNA sequences that Oct4 can latch onto.
DNA is made up of four bases—A, T, G, and C. These bases are arranged one after the other in a certain order. Each person’s set of DNA is a bit different.
Oct4 likes to bind to a certain set of letters—the sequence ATGCAAA. It turns out that this is close enough to a sequence found in the viruses that can come to life, ATGCCAA (the different base is marked in red).
The older, deader viruses do not have the same set of DNA in the same place. They either ACACAGA or ATATAGA. Neither of these are close enough for Oct4 to show any interest.
But having the right bit of DNA nearby isn’t enough. Oct4 has to also be able to “see” the DNA.
Can’t See the DNA for the Methylation
Most of the time the DNA Oct4 recognizes in these viruses is hidden away from it. Like those zombies buried in the ground in Thriller.
Instead of being buried though, the Oct4 DNA is shrouded behind a veil of something called methylation. Basically the cell adds small chemical groups called methyl groups to any DNA it doesn’t want a transcription factor to find. The methyl groups hide the DNA from the transcription factor.
When the researchers looked, they found that the viral DNA that Oct4 recognizes (as well as other DNA around it) is heavily methylated in cells where the virus is off. And those methyl groups are gone when the virus is on.
So to come to life the viruses need Oct4 to be around and for some of its DNA to lose some methyl groups. When this happens, Oct4 can swoop in and bring these viruses back to life.
The researchers have done a great job figuring out the how. Now they need to get cracking on figuring out the why.