Origins of genomic 'dark matter' discovered

Sep 18, 2013
A duo of scientists at Penn State University has achieved a major milestone in understanding genomic "dark matter" -- called non-coding RNA. This "dark matter" is difficult to detect and no one knows exactly what it is doing or why it is there in our genome, but scientists suspect it may be the source of inherited diseases. This research achievement may help to pinpoint exactly where complex-disease traits reside in the human genome. This illustration shows, in the upper left corner, a chromosome -- a densely compressed package containing one long, continuous strand of DNA. The DNA is pervasively transcribed into RNA, but only a very small fraction of the RNA has the instructions (or codes) for making proteins. The green circles in this illustration represent places along the strand of DNA where transcription originates. New research led by B. Franklin Pugh of Penn State University shows that essentially all RNA, whether or not it codes for proteins, originates at the same types of locations along the strand of DNA. The findings eventually may help to pinpoint exactly where complex-disease traits reside, since the genetic origins of many diseases reside outside of the coding region of the genome. Credit: National Institutes of Health and B. Franklin Pugh, Penn State University

A duo of scientists at Penn State University has achieved a major milestone in understanding how genomic "dark matter" originates. This "dark matter"—called non-coding RNA—does not contain the blueprint for making proteins and yet it comprises more than 95 percent of the human genome. The researchers have discovered that essentially all coding and non-coding RNA originates at the same types of locations along the human genome. The team's findings eventually may help to pinpoint exactly where complex-disease traits reside, since the genetic origins of many diseases reside outside of the coding region of the genome. The research, which will be published as an Advance Online Publication in the journal Nature on 18 September 2013, was performed by B. Franklin Pugh, holder of the Willaman chair in Molecular Biology at Penn State, and postdoctoral scholar Bryan Venters, who now holds a faculty position at Vanderbilt University.

In their research, Pugh and Venters set out to identify the precise location of the beginnings of transcription—the first step in the expression of into proteins. "During transcription, DNA is copied into RNA—the single-stranded that is thought to have preceded the appearance of DNA on Earth—by an enzyme called RNA polymerase and, after several more steps, genes are encoded and proteins eventually are produced," Pugh explained. He added that, in their quest to learn just where transcription begins, other scientists had looked directly at RNA. However, Pugh and Venters instead determined where along the proteins that initiate transcription of the non-coding RNA were located.

"We took this approach because so many RNAs are rapidly destroyed soon after they are made, and this makes them hard to detect," Pugh said. "So rather than look for the RNA product of transcription we looked for the 'initiation machine' that makes the RNA. This machine assembles RNA polymerase, which goes on to make RNA, which goes on to make a ." Pugh added that he and Venters were stunned to find 160,000 of these "initiation machines," because humans only have about 30,000 genes. "This finding is even more remarkable, given that fewer than 10,000 of these machines actually were found right at the site of genes. Since most genes are turned off in cells, it is understandable why they are typically devoid of the initiation machinery."

The remaining 150,000 initiation machines—those Pugh and Venters did not find right at genes—remained somewhat mysterious. "These initiation machines that were not associated with genes were clearly active since they were making RNA and aligned with fragments of RNA discovered by other scientists," Pugh said. "In the early days, these fragments of RNA were generally dismissed as irrelevant since they did not code for proteins." Pugh added that it was easy to dismiss these fragments because they lacked a feature called polyadenylation—a long string of genetic material, adenosine bases—that protect the RNA from being destroyed. Pugh and Venters further validated their surprising findings by determining that these non-coding initiation machines recognized the same DNA sequences as the ones at coding genes, indicating that they have a specific origin and that their production is regulated, just like it is at coding genes.

"These non-coding RNAs have been called the '' of the genome because, just like the dark matter of the universe, they are massive in terms of coverage—making up over 95 percent of the . However, they are difficult to detect and no one knows exactly what they all are doing or why they are there," Pugh said. "Now at least we know that they are real, and not just 'noise' or 'junk.' Of course, the next step is to answer the question, 'what, in fact, do they do?'"

Pugh added that the implications of this research could represent one step towards solving the problem of "missing heritability"—a concept that describes how most traits, including many diseases, cannot be accounted for by individual genes and seem to have their origins in regions of the genome that do not code for proteins. "It is difficult to pin down the source of a disease when the mutation maps to a region of the genome with no known function," Pugh said. "However, if such regions produce RNA then we are one step closer to understanding that disease."

Explore further: Preventing the spread of repression

More information: Genomic organization of human transcription initiation complexes, DOI: 10.1038/nature12535

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ohyeah
1 / 5 (1) Sep 18, 2013
initiation machines - wow, incredible
Osiris1
1 / 5 (8) Sep 19, 2013
We best start looking for coded messages in this DNA. Possible the original Bible is in our Human DNA, coded to last the eons and better protected than if it were on gold and hidden in a stony cave......where it could be lost forever. As long as there is a human, the word of God will be written on our hearts just like it metaphorically says in the Bible.
Q-Star
2.3 / 5 (6) Sep 19, 2013
, they are difficult to detect and no one knows exactly what they all are doing or why they are there
In dense aether model the genomic dark matter does the essentially the same things for existing species, like the actual dark matter does for massive bodies. It prohibits the merging of existing genomes, i.e. the cross-species breeding and it maintains the biodiversity. It also prohibits the penetration of small objects into massive objects like sparse atmosphere, i.e. it does serve as a source of immune apparatus.


Zeph, so let me see if I am understanding what ya are saying here,,,,

The AWT and the DAM, applies not only to cosmology and astrophysics, and global warming, and political sociology,,, but now it can also answer fundamental questions in biology? Who would have guessed? I'm really starting to be quite wowed by this AWT & DAM stuff. Actually, I'm beginning to think it is the answer to everything.
Captain Stumpy
1 / 5 (8) Sep 19, 2013
@ Q-Star

with a fanatic, who believes things by faith, instead of through logic or science, there is no such thing as a situation that "does not apply"... case in point: Zeph ... or some fanatical xtian's.

no matter what information may be presented, it will somehow refer to DAM or AWT. this is the logic of blind faith and manipulation of reality to suit.

at least Zeph is not physically dangerous like some other radicals.
Q-Star
2.1 / 5 (7) Sep 19, 2013
at least Zeph is not physically dangerous like some other radicals.


I have a co-worker/colleague who is not so sure about that. He stalks her relentlessly on the internet and she worries he may find airfare and be issued a visa to visit America. (One would hope he is on some sort of "no-fly-list" or "flagged" in some way.)
blengi
1 / 5 (5) Sep 19, 2013
Hmmm kool, one of the more interesting things have read in a while.

Not that I've given much thought, but for the sake of fun speculation:

Perhaps the non coding initiators are there to generate a diffuse background of low persistence RNA fragments, which act like some sublevel heuristic selection bioprocess - a fuzzy RNA fragment cloud biologic if you will. This (RNA fragment cloud) then acts to coordinate and moderate when and which requisite coding section initiators should activate to commit to higher level more persistent protein transcription processes(along with all the other various feedbacks).
blengi
1 / 5 (5) Sep 19, 2013
cont from above:

Apart from perception that such an arrangement would offer a simple primary bio-functional robustness and is perhaps an energetically cost effective solution from point of view various evolutionary trades offs regarding productsof biosynthesis and suchlike; that the notion somewhat squares evolutionarily with say the fuzzy coding cycles of a putative form of early RNA life, tending towards more complex and refined protein dependent coding systems, makes plausibility seem not entirely ridiculous (ok, maybe a tad)...
Captain Stumpy
1 / 5 (8) Sep 19, 2013
@Q-Star
I PM'd you a solution, if you and friend are willing.

the anonymity of the internet makes many a shy fool brazen, and many a coward becomes bold and daring.
Q-Star
3 / 5 (4) Sep 19, 2013
@Q-Star
I PM'd you a solution, if you and friend are willing.

the anonymity of the internet makes many a shy fool brazen, and many a coward becomes bold and daring.


Thanks but it's not necessary, I'd put money on our IT department against the Zephyr any day.
Torbjorn_Larsson_OM
5 / 5 (2) Sep 19, 2013
This doesn't square with ENCODE project, which found this activity but not the proposed function. Meaning most of this RNA is too poorly expressed to do much. The "missing heritability" description (but perhaps not the paper) seems to rely on the faulty one gene-one trait idea.

But it's Ventner. We'll see how this is received by peers.

- I dunno about the creationist this time, a Poe or a self Poe?

- However, the crackpots are hilarious as ever. They claim to have "opponents" when the problem is that they don't have supporters. No one cares about the so called junk science, the "dark matter" of the web trash posing as 'science'.
Captain Stumpy
2.3 / 5 (9) Sep 20, 2013
he stalks her relentlessly on the internet and she worries he may find airfare and be issued a visa to visit America
Why not to keep the subject? It's evident, for coward dumb opponents of AWT every gosip or lie is good enough...;-)


just as it is evident that your pet AWT has no empirical data ... you have YET to answer my post from ages ago in another thread...

and just because you continually repeat something does not make it a fact, or truth. so far, you repeat yourself (under just about every circumstance) and somehow tie your AWT into everything, yet you cannot produce evidence. just talk, and most of that is incoherent, or just reiteration of previously stated comments.

I am usually very skeptical, but I can see that this pattern of behavior fits what you already display, therefore i tend towards belief...
antialias_physorg
5 / 5 (3) Sep 20, 2013
The AWT and the DAM, applies not only to cosmology and astrophysics, and global warming, and political sociology,,, but now it can also answer fundamental questions in biology?

Surely. As you must by now have gathered: AWT is simply a Zeph-translation for:

"I randomly plug buzzwords together and call that a theory - which I then decalre as truth as it fits my intuition. And my intuition is infallible, hence it needs no evidence, experiment or other kind of validation"

It's his version of religion, since it is based on "I don't need to think - I already know"