Junk No More! 80% of the Genome Functional

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posted on Sep, 11 2012 @ 06:28 AM
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Originally posted by Arbitrageur
From what I've read so far, the authors indirectly assert that the 80% figure is "not conservative" which is a sentiment echoed by various blogs by people that seem to know more about this than I do. In other words, a more conservative number would be lower than that at this point. This alone would seem to he reason to downplay the 80% number if even the authors themselves can't fully support it. But I'll know more after I read some of the papers, though that will take some time and I haven't done that yet.


From the paper.


Interestingly, even using the most conservative estimates, the fraction of bases likely to be involved in direct gene regulation, even though incomplete, is significantly higher than that ascribed to protein coding exons (1.2%), raising the possibility that more information in the human genome may be important for gene regulation than for biochemical function.


The 80% figure is one based on an a all inclusive representation of the project.

To quote Birney.


"We had to decide on a percentage, because that is easier to visualize, and we choose 80% because (a) it is inclusive of all the ENCODE experiments (and we did not want to leave any of the sub-projects out) and (b) 80% best coveys the difference between a genome made mostly of dead wood and one that is alive with activity. We refer also to “4 million switches”, and that represents the bound motifs and footprints.

We use the bigger number because it brings home the impact of this work to a much wider audience. But we are in fact using an accurate, well-defined figure when we say that 80% of the genome has specific biological activity."


The project divides the functional regions up in categories, such as RNA transcribed regions, protein-coding regions, transcription-factor-binding sites, chromatin structure, and DNA methylation sites. The largest of which is actually the RNA types.


Accounting for all these elements, a surprisingly large amount of the human genome, 80.4%, is covered by at least one ENCODE-identified element. The broadest element class represents the different RNA types, covering 62% of the genome (although the majority is inside of introns or near genes). Regions highly enriched for histone modifications form the next largest class (56.1%). Excluding RNA elements and broad histone elements, 44.2% of the genome is covered. Smaller proportions of the genome are occupied by regions of open chromatin (15.2%) or sites of transcription factor binding (8.1%), with 19.4% covered by at least one DHS or transcription factor ChIP-seq peak across all cell lines.


You'll find the objections get down to splitting hairs over the word functional. ENCODE defines it as “specific biochemical activity”. Whatever that activity might be. You'll also find many of the objectors having a prior investment in Junk DNA. Coincidence?

Functional does not mean absolutely required or needed. My car doors are functional but it certainly is still a functional car without them. Also gene knockout tests don't consider the fact that the cell can use multiple pathways and can compensate well with the loss of some elements. It only makes sense to have back up systems, yes? Also non conserved does not mean non functional as the paper points out.

It's true, functions for junk DNA have beed discovered since the 90's.
edit on 11-9-2012 by squiz because: (no reason given)




posted on Sep, 11 2012 @ 08:40 AM
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The paper doesn't assert the fact that some 40% of the human genome consists of transposable elements, and another 10% of degenerated retroviruses. I'm having a hard time understanding how these don't count as "junk"..



posted on Sep, 11 2012 @ 10:56 AM
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Originally posted by squiz
You'll find the objections get down to splitting hairs over the word functional. ENCODE defines it as “specific biochemical activity”. Whatever that activity might be. You'll also find many of the objectors having a prior investment in Junk DNA.
Birney himself admits the various definitions of "functional" and discusses some of the issues here along with different percentages:

genomeinformatician.blogspot.co.uk...

Q. So remind me which one do you think is “functional”?
A. Back to that word “functional”: There is no easy answer to this. In ENCODE we present this hierarchy of assays with cumulative coverage percentages, ending up with 80%. As I’ve pointed out in presentations, you shouldn’t be surprised by the 80% figure. After all, 60% of the genome with the new detailed manually reviewed (GenCode) annotation is either exonic or intronic, and a number of our assays (such as PolyA- RNA, and H3K36me3/H3K79me2) are expected to mark all active transcription. So seeing an additional 20% over this expected 60% is not so surprising.

However, on the other end of the scale – using very strict, classical definitions of “functional” like bound motifs and DNaseI footprints; places where we are very confident that there is a specific DNA:protein contact, such as a transcription factor binding site to the actual bases – we see a cumulative occupation of 8% of the genome. With the exons (which most people would always classify as “functional” by intuition) that number goes up to 9%. Given what most people thought earlier this decade, that the regulatory elements might account for perhaps a similar amount of bases as exons, this is surprisingly high for many people – certainly it was to me!

In addition, in this phase of ENCODE we did sample broadly but nowhere near completely in terms of cell types or transcription factors. We estimated how well we have sampled, and our most generous view of our sampling is that we’ve seen around 50% of the elements. There are lots of reasons to think we have sampled less than this (e.g., the inability to sample developmental cell types; classes of transcription factors which we have not seen). A conservative estimate of our expected coverage of exons + specific DNA:protein contacts gives us 18%, easily further justified (given our sampling) to 20%



posted on Sep, 11 2012 @ 12:20 PM
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Originally posted by jiggerj

Originally posted by kennyb72
Why wouldn't the OP present the fact that this little nugget of information strengthens the case for creationism.



It does? All I see is that it strengthens the claim that there is no junk DNA. Plus, do creationists really want to lay the blame for the cancer gene on a competent creator? How about the faulty genes that cause mental retardation, deformities, and all the other genetic diseases. No, you guys don't want to go there.

edit on 9/9/2012 by jiggerj because: (no reason given)


DNA is the software of life.

- Biological Toggle Switches -

Playing God ? or improving mankind?



posted on Sep, 11 2012 @ 08:52 PM
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reply to post by Arbitrageur
 


Yes, he needed to clarify the word has different uses due to the critics, of course you'll get some whining, so many have supported the junk DNA theory they aren't about to let it go that easily. Even if it does involve hundreds of scientists and multiple labs producing 30 or more peer reveiwed publications. Alternativively anything that suggest that parts of the genome are non functional they don't question at all and simply accept it because it supports their view. You wouldn't hear complaints if was said that 80% of the genome is non functional. Funny how that works.

This part might sum it up best.


Q. Hmmm. Let’s move onto the science. I don’t buy that 80% of the genome is functional.

A.It’s clear that 80% of the genome has a specific biochemical activity – whatever that might be. This question hinges on the word “functional” so let’s try to tackle this first. Like many English language words, “functional” is a very useful but context-dependent word. Does a “functional element” in the genome mean something that changes a biochemical property of the cell (i.e., if the sequence was not here, the biochemistry would be different) or is it something that changes a phenotypically observable trait that affects the whole organism? At their limits (considering all the biochemical activities being a phenotype), these two definitions merge. Having spent a long time thinking about and discussing this, not a single definition of “functional” works for all conversations. We have to be precise about the context. Pragmatically, in ENCODE we define our criteria as “specific biochemical activity” – for example, an assay that identifies a series of bases. This is not the entire genome (so, for example, things like “having a phosphodiester bond” would not qualify). We then subset this into different classes of assay; in decreasing order of coverage these are: RNA, “broad” histone modifications, “narrow” histone modifications, DNaseI hypersensitive sites, Transcription Factor ChIP-seq peaks, DNaseI Footprints, Transcription Factor bound motifs, and finally Exons.


I think he clarifies it pretty well.

"Specific biochemical activity" is clearly present in 80% of the genome linked through the different classes of assay. The specifics of that activity isn't readily known. Claiming almost every nucleotide is associated with a function of some sort is not a small statement in anyway at all.

I've been thinking about this...

It's believed that repetitive DNA may work as fine tuning for body parts, eg. the curvature of a nose. defined in the amount of repetitions. This is functional but it is not really a selectable trait. Does that make it junk?

We share 96% genetic simililarity with chimps. This number only compares the coding sequences that make up less than 2% of the entire genome. It's very likely that much of the non coding regions may be more species specific.

The Chimps genome is 10 to 12% larger, the similarity between the whole genomes is actually more in the range of 70 to 75%. This may surprise many people but it is true.

Clearly we are more than 4% different in both appearance and behaviour, it seems obvious that much of what makes us different may be described in the non coding regions. The comparable differrence makes much more sense even by simple observation under the differences between the whole genome and not just the coding DNA.

Just a thought.



posted on Sep, 11 2012 @ 08:59 PM
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I thought of something today which will hopefully clarify the issue.

the term "junk" DNA was coined as referring specifically to all genomic SEQUENCES not coding for a SPECIFIC product.....somewhere around 97% of the genome.

note the word "sequence" above.

it should be clear by now that the functional elements which are mapped in this new library are (generally) independent of the sequence.

since this additional regularatory information does not reference a functional sequence, the sequence is still junk,...according to the original definition.


and now, a metaphor.

if you take a road trip to Las Vegas, you will follow a sequential pathway to arrive at your destination. certain locations along that sequence serve a very specific purpose, such as the gas station. let us call these primary and secondary destinations, functional sequences, genes, not junk.

as for the rest of it....well. it does certainly does have some type of function or another, now doesn't it? but in general, signposts and lane demarcations on the pavement could be said to be independent of the underlying sequence. the sequence, itself, could be nearly anything.....it is the TAG on the sequence that is important.

what's more, there is nary a single yard of ground covered on the trip which does not contain some type of information.



so, when you tell me that approaching 100% of the DNA has functional content, as a biotechnician I am like, "....yeah. no kidding."

but that still does not change the fact that the majority of it really doesn't do all that much.

and if you're going to tell me that we are going to reclassify the "junk", I am really expecting something very very special.



posted on Sep, 11 2012 @ 09:12 PM
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reply to post by squiz
 


I am finding it bordering offensive that you are constantly referring to the "usual suspects" as having an agenda, and other derogatory references.

while I agree with much of what you say, it is clear to me that you, also, have an agenda.

you immediately take their (my) comments to be suspicious without considering that just maybe they (I) am operating with more information than you.

I have my own pet theories about the true nature of the junk sequences. most scientists are not nearly as closed minded as you seem to imagine.



posted on Sep, 11 2012 @ 09:47 PM
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reply to post by tgidkp
 


Well, that should be simple enough.



posted on Sep, 11 2012 @ 10:04 PM
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reply to post by tgidkp
 


Well that is your problem, I was not including you. Your free to make any comments you feel. Relax dude. You've been respectfull, unlike those I'm referring to.

The usual suspects that I refer to are a small but vocal group that have a long history in regards to this issue as well as being quite repulsive, rude, insultng and arrogant. They are not driven by science but by ideologies. I've been observing the debate on both sides for quite a while. The reaction says quite a bit. I wasn't going to give names or personalise that would only put me on the same level as them.

Your comments don't bother me, they do seem at odds with what the researchers are saying IMO. Why should mine bother you? Especially when you don't know who I'm actually referring to. Unless you yourself have a bias? You simply seem to be saying if it doesn't reference protein production it's junk. I don't agree with that one bit. Neither does the evidence or the researchers it seems. Your opinion is your own of course.

Yes I am biased towards design as I suggested in my second post, and for a very good reason, semiosis.

However I accept evolution, I accept the possibility of a common ancestor, I accept natural selction, random mutation etc.. As far as evolution goes I refer to other ideas such as natural genetic engineering. McClintock, Shapiro etc...

In this view much of what you are writing off is vital for the evolutionary process!

I also accept the findings of this project.
We've known for a long time much of what was thought to be junk isn't, is it really that surprising? It doesn't confirm anything one way or the other but it has been used to do so for a very long time. That's the bottom line.

My agenda is revealed. Muhahahaha!
edit on 11-9-2012 by squiz because: (no reason given)



posted on Sep, 11 2012 @ 10:13 PM
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The junk DNA is just a record of our ancestors eating habits and immunity. It is what causes the response to different situations. This junk DNA is who we are, the regular DNA is what we are.

The interactions with food chemistry are recorded in this junk and when a piece of metal Ion breaks off it sends a signal which triggers a response from the body or a craving for an antidote to balance the system. It would be nearly impossible to research the information in this junk DNA but our subconscious does it within seconds of a problem or set of problems occurring. I've added this last part so it's not proven yet, just a hypothesis of mine.



posted on Sep, 12 2012 @ 04:55 AM
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Here's another video. Although older it's very informative although It's a bit more technical. There's some fascinating information in here. It also may answers a few questions that have come up.

edit on 12-9-2012 by squiz because: (no reason given)



posted on Sep, 12 2012 @ 08:00 AM
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One of the problems that is occurring presently is that the junk DNA's interaction with the use of Pharmacology has been ignored previously by the industry because there is no undeniable proof that altering the Junk DNA had any relationship to the drug industry. Hopefully this information will help identify side effects of long term medication use in the future. Many people have been put on long term medications without any acknowledgement of side effects. Maybe this will also help to deter the use of new and existing chemicals used on food preservation of our foodstuffs. There is presently little long term testing or genetic evaluation done on these changes to food chemistry. Presently evaluating long term effects of new chemicals is not required by our government because it interferes with profits of getting the food to market. If we ate more locally grown foods we would be better off. Making beet greens stay fresh looking for a week to be appealing to customers is causing problems. I choose beet greens as an example because I know beet greens seem to turn wilty within a day normally even if misted with water.



posted on Sep, 12 2012 @ 03:53 PM
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reply to post by rickymouse
 


you make a very good point, one which i think points to the REAL ACTUAL purpose of making this type of genetic data available.

in the following article, you can read about one of the best cases that people make for epigenetics actually being more important than genetics.

Cancer-Linked Epigenetic Effects of Smoking Found



posted on Sep, 12 2012 @ 10:15 PM
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reply to post by tgidkp
 


This subject is a lot more necessary than playing with remote control toys on mars and the moon.



posted on Sep, 12 2012 @ 10:30 PM
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Originally posted by de_Genova
YO Pinke - Am I invited toooooooo?

FYI - Clear headed thinkers have always said that God doesn't make junk.......the criminal scientific atheistic community invented the term "junk DNA" to further their evolutionary nonsense - DNA and the human genome is the language of God - "THE WORD" - people like Dawkins and Hawking et al., in comparison produce "Gangsta Rap" - atheistic fools.........in denial of God's wonder of creation.
edit on 10-9-2012 by de_Genova because: pre-


You could try and get fighter status from the debate forum, Genova.

You might have a bit of a hiccup with your WATS score, I'm not sure. Mods would have to tell you. In this context scientists were one of the first to point out that 'junk DNA' is not a 100% correct term, so I wouldn't agree with you.



posted on Sep, 12 2012 @ 10:45 PM
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reply to post by Pinke
 


I don't mind it being called junk DNA. I got lots of junk. To me and half the people in the country my junk is good junk while the other half think it's bad junk. I think Rembrandt pictures and Tiffany are just everyday junk, not anything that impresses me, so I suppose I don't mind. Everything is junk, even DNA



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