Scientists discover ancient viral invasion that shaped human genome

Jun 07, 2010

Scientists at the Genome Institute of Singapore (GIS) and their colleagues from the National University of Singapore, Nanyang Technological University, Duke-NUS Graduate Medical School and Princeton University have recently discovered that viruses that 'invaded' the human genome millions of years ago have changed the way genes get turned on and off in human embryonic stem (ES) cells.

The study provides definitive proof of a theory that was first proposed in the 1950s by Nobel Laureate in physiology and medicine, Barbara McClintock, who hypothesized that transposable elements, mobile pieces of the genetic material (DNA), such as viral sequences, could be "control elements" that affect gene regulation once inserted in the genome.

This finding is an important contribution to the advancement of stem cell research and to its potential for . Led by GIS Senior Group Leader Dr Guillaume Bourque, the study was published in on June 6, 2010.

Through the use of new sequencing technologies, the scientists studied the genomic locations of three regulatory proteins (OCT4, NANOG and CTCF) in human and mouse embryonic stem (ES) cells. Interestingly, while the scientists found a lot of similarities, they also found many differences in the methods and the types of genes that are being regulated in humans. In particular, it was discovered that specific types of viruses that inserted themselves in the human genomes millions of years ago have dramatically changed the gene regulatory network in human stem cells.

"This study is a computational and experimental tour de force. It provides undeniable evidence that some transposable elements, which are too often dismissed as merely , are key components of a regulatory code underlying human development," said Dr Cedric Feschotte, Associate Professor of the University of Texas Arlington.

The comparisons between the human and mouse model system in the study of gene regulatory networks help to advance the understanding of how stem cells differentiate into various cell types of the body. "This understanding is crucial in the improved development of regenerative medicine for diseases such as Parkinson's disease and leukaemia," said Dr Bourque. "Despite the advantages of using mouse in the study of gene regulatory networks, further research must focus more directly on human stem cells. This is due to the inherent challenges of converting the results of studies done from one species to that of the next. More research will need to be done in both human and non-human primate stem cells for findings on to be used in clinical application."

Prof Raymond L. White, PhD, Rudi Schmid Distinguished Professor of Neurology, University of California said, "The paper reports very exciting new findings that establish a new and fundamentally distinct mechanism for the regulation of gene expression. By comparing the genomes of mouse with human, the scientists were able to show that the binding sites for gene regulatory factors are very often not in the same place between the two species. This by itself would be very surprising, but the investigators go further and demonstrate that many of the sites are imbedded within a class of DNA sequences called "transposable" elements because of their ability to move to new places in the genome. There are a number of such elements believed to be the evolutionary remnants of viral genomes, but it was very surprising to learn that they were carrying binding sites for regulatory elements to new locations. These changes in regulation would be expected to create major changes in the organisms which carry them. Indeed, many think that regulatory changes are at the heart of speciation and may have played a large role in the evolution of humans from their predecessors. This is likely to be a landmark paper in the field."

Dr Eddy Rubin, Director of the U.S. Department of Energy Joint Genome Institute and Director of the Genomics Division at Lawrence Berkeley National Laboratory in Berkeley added, "This study using a comparative genomics strategy discovered important human specific properties of the regulatory network in human ES cells. This information is significant and should contribute to helping move the regenerative medicine field forward."

Explore further: Scientists develop genome-wide mutation hunting computational software for genomic medicine

Provided by Agency for Science, Technology and Research (A*STAR)

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xamien
5 / 5 (1) Jun 07, 2010
What doesn't kill you makes you stronger...
LuckyBrandon
2 / 5 (2) Jun 07, 2010
That is true, but what I get from this is that a certain type of virus could potential alter the evolution of a species...
I would think that could include the eventual die off of a species too...
I mean, if they moved a piece of "code" from place A to place B that while in place A was responsible for the creation of, let's say, a single chamber of the heart, then that could lead to a weaker heart in that species, or worse, such as if such a change would automatically cause the other areas responsible for making the heart to not make it at all...obviously, that could be a problem....
Just thinking out loud...
PinkElephant
5 / 5 (2) Jun 07, 2010
@LuckyBrandon,

Viruses don't work like that. The way viruses insert themselves into the human genome, is by infecting germ cells (sperm or the egg) prior to fertilization, or by infecting a part of the early fetus that will later form its genitals (quite a bit less likely.) If such viral-induced mutations make the embryo nonviable, or impart selective disadvantages to the offspring of the organism (provided the organism gestates successfully and survives to adulthood), then they will be weeded out of the population in short order.
Djincs
not rated yet Jun 08, 2010
Such locuses exist, they have a big role in the evolution, the DNA has its way to rearrange the information in lots of way, allso there is debate wether the viruses infected the sells and that is how we have this transposable elements in the DNA or such elements have escaped and created the viruses.
The chance for a rearrangement to be successful is really low, actually 30% of the embrios are dying in the furst week because there is no sense mutation, 3% of the newborn have some non deadly or mutation that is not manifested phiziologically, but still this is small price to pay in the name of progress, this is the nature way...even if only 0,0001% of the rearangement have eny sense and they are beneficial, this will justify all the "victims" of this proces.
LuckyBrandon
1 / 5 (1) Jun 09, 2010
There was another article on this site talking about transposable viral infections moving laterally...that would indicate that it does not need to affect the fetus...
If that were the case, then why do viruses we get sick with today bind to our genes?
By no means is this my expertise, I'm just curious, and saw another article that at least made it sound as if a parralel viral move into the genetic code can and will be done....
I tried my best to find the article to link it but couldnt find it...
PinkElephant
not rated yet Jun 09, 2010
@LuckyBrandon,

Yes, there's a class of viruses (retroviruses, to be exact) that incorporates itself into the host cell's DNA.

However, such infections cannot give rise to /heritable/ genetic changes, unless they manage to infect germ cells, AND somehow become disabled/inactive subsequently to infection.

Also, such infections cannot cause your heart to reconfigure its number of chambers: such structure is set up once and for all quite early during embryonic development. Infecting an embryo is much more difficult for a virus, because the embryo is very well protected in the womb.

Lastly, normal viral infections affect only a small percentage of your cells. (The cells that get infected, ultimately die from it or are destroyed by the immune system.) If a significant percentage of your cells got infected by an active virus, you would not survive the infection.
LuckyBrandon
Jun 11, 2010
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