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Stealing genes from HERV-H may have offered a safer way to induce pluripotency in primate embryos

Viruses were traditionally thought to be malicious nanoscopic bearers of death and destruction.  But modern science has suggested that while that is sometimes the case, the relationship between viruses and living organisms is a complicated one, as is the question of whether viruses can be truly considered "living" organisms.
 
I. Viruses Can Actually be Useful, Sometimes
 
In case newly discovered mega-viruses -- which rival small bacteria in size, function, and genetic complexity (and are sometimes "infected" by other viruses) -- aren't mind-warping enough, recent evidence suggests that as much of 8 percent of the genetic material found in higher organisms such as humans may be "borrowed" from viral genomes.  These pieces of DNA are identifiable, if you know what you're looking for, but long ago lost their ability to depart and jump to new hosts.
 
In that regard, mankind can be viewed as similar in some ways to lichen -- as a collection of multiple fused "organisms" living as one -- as modern man's genetic code consists of virus and traditional eukaryotic genes functioning side by side.
 
The latest wild discovery comes courtesy of Montreal, Quebec, Canada's McGill University.

Guillaume Bourque
McGill University epigenetics expert, Professor Guillaume Bourque [Image Source: PRI]

McGill Computational Biology Professor Guillaume Bourque suggests in a new paper just published in Nature Structural & Molecular Biology that the production and operation of stem cells in primates are heavily dependent on endogenous virus genes from the human endogenous retrovirus subfamily H (HERV-H).
 
Professor Bourque's work may be controversial, but it is also brilliant.  He is one of the world's eminent experts on gene sequencing and the complicated field of epigenetics -- the study of how genes arise and how they assemble in the presence of a rich poly-molecular cellular environment.
 
Several lines of eukaryotes  -- including plants and animals -- have "stem cells", cells which are known as "multipotent", meaning they can transform into various types of tissues when the need arises.  A few examples of common tissues in an animal include bone, muscle, and skin.  Sometimes the transformation is permanent (e.g. in the case of a liver cell), other times the cell remains weakly pluripotent, able to differentiate (transform) into some reduced tissue subset (e.g. bone marrow progenitor cells that can become red or white blood cells, alternatively).

Stem cell
Embryonic stem cells can become whatever tissues the developing embryo needs, locally.
[Image Source: Corbis]

Embryonic stem (ES) stem cells are a special type of stem cell that play a role early in organisms' development.  Sometimes called "ESSCs", these stem cells are found in a broad array of eukaryotes including fish, mice, and humans [source].  Fish -- the oldest vertebrate family -- are thought to have evolved roughly half a billion years ago.  While it is unknown whether the earliest fish had ESSCs that allowed their embryos flexibility to grow quickly and differentiate into complex, multi-tissue organisms, it's clear that modern fish have this capacity.

Induced Pluripotency
[Image Source: Cell]

Professor Bourque suggests that a growing body of evidence supports the theory that sperm and egg cells of multicellular eukaryotes are often "infected" with retroviruses -- the name given to viruses like HIV (the "AIDS virus") which insert their genetic code into the DNA -- and in the process gain useful adaptations.  Given the exchange of genetic material that occurs during meiosis, it's possible that the virus is irreparably broken.
 
That means the offspring can gain potentially useful capabilities of the virus, genetic code that remains trapped with no means of escaping, for lack of the rest of the virus's latent genome.  Such trapped/acquired viral genes are known as "endogenous viral DNA".
 
II. HERV-H: Primate's Little Helper
 
HERV-H has been known for some time to be viral DNA -- not originally from eukaryotic evolution.  But it was thought to be mere "junk" as most endogenous viral genes were long dismissed as.  But Professor Bourque has shown that HERV-H expression plays a critical role in keeping ESSCs in humans pluripotent.
 
The discovery is particularly fascinating as the human medical community itself has followed a similar road in inducing pluripotency in other kinds of cells (e.g. skin cells).  The general premise of those studies was creating novel retroviral vectors, and using those tiny viruses to insert genes into a human cell or test animal's adult (differentiated) cells to coax them to regain pluripotency.
 
HERV-H is unique to primates and is thought to have entered the genome via infection of egg and/or sperm lines some 20 million years ago.  Now, the human genome has roughly 1,000 copies of the potentially crucial gene.
 
HERV-H influences transcription by promoting OCT-4, a well-studied gene known for inducing pluripotence (and also known as playing a role in cancer as a so-called "oncogene").
HERV-HHERV-H induces pluripotency by acting on OCT-4. [Image Source: Nature Struct. & Mol. Bio.]

While non-primates don't typically have HERV-H genes and don't seem to need them, it's entirely possible that they borrow other viral genes to induce pluripotentcy or to accomplish other useful work.

Professor Bourque states in an interview with National Geographic:

[Acquiring useful genes from viruses] can be faster than just relying on random mutations to get something that might work.

Harvard University functional genomics Professor John Rinn (not affiliated with the work) suggests that by monitoring other known viral genes more surprises may be discovered.  He comments:

[These genes should be examined] to see if they have also evolved new functional roles, like HERV-H did in stem cells.  We suspect that these genes may play important roles in other cell types as well, such as liver, kidney, and brain.

While I found this study interesting, I think it's worth noting that the authors have yet to fully explain why mankind relies HERV-H for pluripotentcy.  One possibility I would propose is that perhaps the gene was useful in dealing with the increasing complexity in primate tissues (primates have considerably more complex organ systems that a rodent, for example).

Chimpanzee thinking
Primates rely on the borrowed powers from HERV-H to create their embryonic stem cells.
[Image Source: WWF]
 
Another possibility is that the gene allowed more selective induction of pluripotentcy, reducing cancer risk -- a common problem in pluriptent tissues.  Cancer is much more dangerous to primates than lower mammals such as lab mice because -- simply put -- humans and other primates breed slower.  That makes loss of an embryo to cancer much more catastrophic.
 
Assuming that HERV-H may somehow reduced cancer risks in induced pluripotent stem cells (including the special ESSC variety), that could be a boon to stem cell therapies that are being explored as treatments for a wide variety of medical problems including cancer, paralysis, heart attack, Alzheimer's disease, and Parkinson's syndrome.  Mr. Bourque seems to echo this possibility stating, "[The discovery of HERV-H's role] could help lead to regenerative medicine therapies."
 
That sounds like good news to us.

Sources: NATURE STRUCTURAL & MOLECULAR BIOLOGY, National Geographic



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Very cool
By sgw2n5 on 3/31/2014 9:36:44 PM , Rating: 2
A large portion of the eukaryotic genome is derived from viruses, but also various other transposable genetic elements which may or may not have been of viral origin. Molecular biology and genetic research is absolutely booming now thanks to next gen sequencing. Amazing stuff.




RE: Very cool
By Da W on 4/1/2014 11:23:26 AM , Rating: 2
DNA is coded information. It makes sence this information comes from *something*, like viruses, as opposed to the theory that DNA mutation just happened out of thin air.


RE: Very cool
By sgw2n5 on 4/1/2014 12:02:10 PM , Rating: 2
I don't think there is any theory that DNA mutations come from thin air...

There are many many ways to get sequence variations (or de novo sequence) into a given genome. Oxidative damage, ionizing radiation, double stranded break repair, gene duplication events, etc. that are completely independent of viral infection (or endogenous transposable elements).


Oh My God...
By Reclaimer77 on 4/1/2014 9:26:37 AM , Rating: 2
The X-Files had it right!!??

Mind...blown.




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