Ancient virus found hibernating in the human genome—and it might wake up
by Beth Mole - Mar 24, 2016
Scanning electron micrograph of HIV-1 budding (in green) from a human cell.
In DNA dig, scientists unearth more viral code, which makes up >8% of our genomes.
In the current era of microbiome research, us humans are already having to come
to grips with the fact that ‘I’ is actually ‘we’. Instead of our bodies constituting
a single life-form, we are each comprised of complex and diverse ecosystems of microbes
that have a profound influence on our existence. Our health and wellbeing are not just
determined by what our own cells do, but what our trillions of invisible inhabitants
do, too. And the genetic blueprints that govern our biology are partly carried in those
microbial inhabitants, as well as in our own cells.
But, as it happens, the DNA in our own cells isn’t solely ours, either. More than eight
percent of the human genome is not human at all—it’s from viruses. And scientists are
still digging up yet more viral code from human DNA that may well influence our lives.
In a new study this week, researchers analyzed the genomes of more than 2,500 people
and found 19 never-before-noticed segments of viral genetic code. Some of that viral
DNA may have been traveling down human lineages for at least 670,000 years, the researchers
reported in the Proceedings of the National Academy of Sciences.
Most of the genetic sequences are mere remnants of long-gone viral particles. Still,
previous research has found evidence that such fragments may influence the development
of diseases, such as cancer and autoimmune disorders, based on their activity or
placement near human genes.
But, perhaps more interesting, the researchers also found a segment of viral code that
appeared to be completely intact and, when activated, may resurrect an ancient virus.
"This one looks like it is capable of making infectious virus, which would be very exciting
if true, as it would allow us to study a viral epidemic that took place long ago," senior
author and virologist John Coffin, of the Tufts University School of Medicine, said in a press release.
The researchers are now working out whether the code can generate a fully functional virus.
So far, this gene segment, dubbed Xq21, is only the second known instance of a complete viral
code—called a provirus—lurking in the human genome.
The researchers started their molecular dig to find viral fragments after several previous
studies had hinted that they may be involved in disease. These sequences, called human
endogenous retroviruses, or HERVs, are actually DNA versions of RNA-based viruses
that permanently lodge their code into human DNA—a class of viruses called retroviruses.
(HIV is an example of a retrovirus.) Over time, the viral codes break apart from mutations,
deletions, and/or recombining with other DNA fragments. Nevertheless, they can still have
effects—they may mess up nearby genes, become partly activated and contribute to disease,
or evolve into new genes that are co-opted by human cells.
"Many studies have tried to link these endogenous viral elements to cancer and other
diseases, but a major difficulty has been that we haven't actually found all of them yet,"
said co-first author Zachary Williams, also at Tufts.
To find more viral sequences, the researchers used two new DNA analysis techniques that
look for hybrid DNA fragments and seams of where viral DNA patched itself in. Such pieces
may have been discarded in previous analyses as garbled code. The method not only found
19 new viral fragments, it confirmed 17 previously identified fragments—which helped assure
researchers that the method works.
Of course, not all of the fragments were found in all of the genomes surveyed. In fact,
some were only found in a few genomes, while others were present in more than 75 percent.
The provirus, Xq21, found on the X chromosome, appeared to be in 44 samples.
While the researchers work to see if the forgone germ can be revived, the researchers
are hopeful that their method could be used to study more ancient, viral remains that
litter our genomes.
Proceedings of the National Academy of Sciences,
2015. DOI: 10.1073/pnas.1602336113