Science by University of Utah geneticists Cédric Feschotte, PhD, Nels Elde, PhD, and Edward Chuong, PhD, looks at how our bodies have repurposed the viral remnants to defend ourselves against infections by viruses and other pathogens. Feschotte and Chuong explain the research and why our defenses, and those of other mammalian species, may have arrived upon this solution repeatedly throughout evolution.">

Tags: u0762355, infectious disease, dna, virus, genetics

Mar 2, 2016 — It may be unsettling to realize, but roughly eight percent of our DNA is viral in origin, meaning it came from infections our ancestors battled long ago. New research published in the journal Science by University of Utah geneticists Cédric Feschotte, PhD, Nels Elde, PhD, and Edward Chuong, PhD, looks at how our bodies have repurposed the viral remnants to defend ourselves against infections by viruses and other pathogens. Feschotte and Chuong explain the research and why our defenses, and those of other mammalian species, may have arrived upon this solution repeatedly throughout evolution.

Interview

Interviewer: Eight percent of human DNA originally came from viruses. A new study published in "Science" reveals how our body is putting these viral remnant to work.

Announcer: Examining the latest research and telling you about the latest breakthroughs. The Science and Research Show is on The Scope.

Interviewer: I'm talking with the University of Utah Geneticists Dr. Cedric Feschotte and Ed Chuong, who've published a study in "Science" together with collaborator Nels Elde. Scientists for a while have known that some of our DNA comes from viruses. So I don't about you, but I actually find it kind of uneasy to think that I'm not just me, I'm part virus.

Dr. Feschotte: Eight percent of our genome is viruses, but then another 40% on top of that is actually other kinds of selfish genetic elements as well. So one might even say you're less human than you think. Definitely, a huge portion of the genome is represented by these kinds of selfish elements that most scientists often dust under the rug, so to speak.

Interviewer: What you've shown is that our body actually uses some of that foreign DNA for a very specific purpose. What did you find?

Ed: Yes, what we found is that some of these pieces of viral DNA being recycled to serve now some set of functions. Important for the defense of cells against pathogens including viruses.

Interviewer: How did the viral DNA get there in the first place?

Ed: There are remnants of past viral infections that have actually plagued our primate ancestors many, many millions of years ago. And they are descendants and they are been assimilated in the genome of the host and now what we are seeing still is that still some of these elements retain some of the properties, ancestral properties, regulatory properties of these viruses.

Interviewer: So tell me again what you think they're doing. How they're interacting with the rest of the defense system?

Dr. Feschotte: Your body has many ways to sense infection by virus or other kinds of microbes. And one of the first things that happen is that when you sense infections, cells will release, the signal, the warning signal called interferon. In the genomes of our cells there are hundreds of genes that are dedicated to fighting infection, fighting micros, fighting virus but they're normally turned off. Then what happens is when you have responses like the interferon response turned on, these cells sort of awaken from dormancy and then turn on and do their business and eventually sort of turn off. And what we found, basically, was that in addition to a lot of human DNA that gets activated by the signal, a lot of viral pieces are activated as well as thousands of viruses seem to be activated by the interferon response.

Interviewer: So these elements, these viral pieces are basically like triggers that help set off the immune weapons that they're sitting next to?

Dr. Feschotte: When we think about the switches, their original evolved function, so to speak, was to drive transcription of that virus. So I think, initially, 50 million years ago, that was the purpose. But clearly over time, some of these elements have been collocated or domesticated, you know there's different words for it by their host, in this case primates to act then exactly as you say, to act as switches that now instead of turning on viral genes, now they turn on genes that are pivotal for our own immune defenses.

Interviewer: Kind of the cool thing is that you're thinking of this as sort of a coordinated system.

Dr. Feschotte: You can imagine, no one protein is going to be enough against the pathogen. Our strategy is essentially the throw in hundreds of genes that together collectively make a very strong and robust defense system. And I mentioned earlier that the regulation of genes in response to interferon is governed by little molecular switches called regulatory elements. And our question was really, know how do these regulatory elements get there. How do they evolve in the first place? And one idea is that these regulatory elements can sort of evolve through mutation, the code necessary to turn on these genes or response interferon. But what we found was this potential mechanism where these endogenous retroviruses are actually providing these switches.

And what makes that mechanism so attractive is that these endogenous retroviruses have this built in ability to copy and paste themselves throughout the genome. And so if we are trying to think about how do you evolve a coordinative response? Well, it's a lot easier to take a pre bill switch provided by these viruses that are so common in the genome rather than to a sort of "rely" on random mutations to build these switches.

Ed: One reason why we think this mechanism of spreading these elements might be a good way to wire these networks and distribute these switches is that, indeed, the switches already existed. And again, they were serving probably viruses to begin with, but you didn't have to reinvent them.

Interviewer: Do you have evidence that this isn't a one-off thing? That this is happening kind of over and over throughout evolution and in different species too, right?

Ed: Yes, well, this was really another surprise that came kind of late into the study. And what we realized is that some of the elements that were similar are not identical. But very similar to the ones we would see in the human genome and in other primate genomes were actually also present in [inaudible] genome. Now a different location in the genome, but they had the same regulatory properties, it seems. That it contained some of these switches to respond to this infection, essentially. We see them present in multiple species and, indeed, we speculate that maybe the same mechanism has also spread some of these switches in other species to wire their own lineage-specific network of these immunity genes.

Interviewer: Do you think these viral DNA pieces might be impacting our health in other ways?

Ed: Yeah, so we think this is something really interesting that we need to follow up on. Because some of the genes that we found to regulated by this viral DNA have been implicated in cancer, autoimmune disease, they are themselves mis-regulating this disease. And we also know that some of this retroviral DNA is often activated in the same conditions. So now we've sort of connected the dots and are thinking that this provided mechanism can explain some of this mis-regulations of these genes in cancer and in autoimmune disease, but have been co-opted for a new regulatory function.

Announcer: Interesting, informative and all in the name of better health. This is The Scope Health Sciences Radio.