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.
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