Researchers discover ancient virus DNA remnants necessary for pluripotency in humans

Mar 31, 2014 by Bob Yirka report
Human embryonic stem cells in cell culture. Credit: Wikipedia.

(Phys.org) —A team of Canadian and Singaporean researchers has discovered that remnants of ancient viral DNA in human DNA must be present for pluripotency to occur in human stem cells. In their paper published in the journal Nature Structural and Molecular Biology, the team describes how they disabled a viral remnant in stem cell samples and discovered that doing so prevented the stem cell from being able to grow into all but one type of human cell.

All of the cells in the human body start out as —the ability of such cells to do so is known as . Scientists don't really understand how individual stem cells know which type to become but are working hard to find out—it could lead to the development of cures for many diseases or the regeneration of lost limbs. In this new effort, the researchers wondered about the role of remnant viral DNA in stem cell DNA and pluripotency in general.

Scientists have known for some time that viral DNA exists in human DNA, the result of retrovirus infections millions of years ago. Retroviruses reproduce by injecting their own DNA into the DNA of a host—if it occurs in sperm or , the virus DNA can end up in the DNA of the host. Until now, scientists have thought that remnant viral DNA was simply "junk" DNA—meaning it didn't do anything at all. Now it appears clear that at least one type of such DNA—HERV-H—actually plays a very important role in pluripotency.

The researchers treated some human stem cells with a small amount of RNA designed to suppress HERV-H. Doing so, they found, removed the stem cell's ability to develop into any human cell—instead they would only grow into cells that resembled fibroblasts—cells normally found in connective tissue. A closer look revealed that suppressing HERV-H also suppressed the production of proteins necessary for pluripotency. Thus, at least in humans, the remnant viral DNA appears to be necessary for normal human development—without it, human life would be impossible.

Because of the role HERV-H plays in pluripotency, its possible other remnant viral DNA plays a role in human development as well, thus it's very likely that other research efforts will focus on testing each to see if they are more than just junk left over from infections over the course of human evolution.

Explore further: Critical factor (BRG1) identified for maintaining stem cell pluripotency

More information: The retrovirus HERVH is a long noncoding RNA required for human embryonic stem cell identity, Nature Structural & Molecular Biology (2014) DOI: 10.1038/nsmb.2799

Abstract
Human endogenous retrovirus subfamily H (HERVH) is a class of transposable elements expressed preferentially in human embryonic stem cells (hESCs). Here, we report that the long terminal repeats of HERVH function as enhancers and that HERVH is a nuclear long noncoding RNA required to maintain hESC identity. Furthermore, HERVH is associated with OCT4, coactivators and Mediator subunits. Together, these results uncover a new role of species-specific transposable elements in hESCs.

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3.8 / 5 (5) Mar 31, 2014
Makes one wonder how many other life forms are so dependent and when did this alignment become a matter of pluripotency - is this virus remnant present in ancient plants, dinosaurs or even ancient mammals? Was this the same method employed throughout the human and near human family? Neanderthal and Homo Sapiens, and Homo Erectus...etc, etc, etc, was this the ONLY way to introduce pluripotency?

word-to-ya-muthas
antialias_physorg
4.9 / 5 (7) Mar 31, 2014
is this virus remnant present in ancient plants, dinosaurs or even ancient mammals?

It should be present in all types of fauna/flora that start from a single cell and then differentiate (which means basically everything except unicellular organism ...and possible some early colony forming organisms like Volvox)
shavera
4.3 / 5 (6) Mar 31, 2014
aap: not necessarily. It could be that the HERV-H addition doubled some function, then the "native" function was disabled through some other mutation, but HERV-H continued to prevent that organism from dying. Or some other adaptive mechanism whereby the organism takes advantage of this new genomic material to replace extant material. (disclaimer: i'm a physicist not a biologist, so maybe i'm really wrong)
Dr_toad
Mar 31, 2014
This comment has been removed by a moderator.
tekram
5 / 5 (8) Mar 31, 2014
HERVH is a primate-specific endogenous retrovirus (ERV), so it goes back about 8 million years. It is apparently not present in mice.

http://www.nature...SF1.html
RhoidSlayer
4.4 / 5 (7) Mar 31, 2014
pluripotency has been a building block of life for billions of years ?

isn't blocking HERV-H and saying all life depends on remnants of viral dna like blocking a road and saying all traffic requires remnants of one of the cars
russell_russell
5 / 5 (1) Apr 03, 2014
Natures' insult to injury. The injury from humans calling what she does junk.
Great news.
russell_russell
5 / 5 (1) Apr 03, 2014
Tekram's remark answers the question of RhoidSlayer:

...apparently not present in mice - this specific 'remnant' - to bypass 'blocked' roads.

Can be use to solve evolutionary "bottlenecks" though.
Tangent2
not rated yet Apr 03, 2014
Until now, scientists have thought that remnant viral DNA was simply "junk" DNA—meaning it didn't do anything at all.


Right, everyone knows that Nature likes to do things for nothing and be wasteful.
I think it is long overdue to rethink this ignorant stance.