[atratus]

It's important to be wary of the term 'junk DNA'...just because a segment of a chromosome is noncoding does not mean it has no role in the genome's function. Assembly of functional structure ie a Replisome requires formation of elaborate secondary and tertiary 3-D conformations that support the primary replication machinery. This is facilated by topoisomerases, binding proteins, a whole soup of RNAs, and spans of "junk" which allow the necessary conformations. In other cases, the 'junk' can serve to insulate highly conserved genes. "Junk" is a terrible characterization.

This is one of those instances where the press/pop media can be a bit behind. Some bchem textbooks from even a few years ago are obsolete. Research into DNA-DNA interaction really has become hotter in only the last few years as we've begun pinning down protein roles. There is a whole layer of interaction between epigenetics, differential RNA splicing, and DNA-DNA feedback that is just mind-boggling.

[fabian2k]

It's very annoying how the media, and sometimes even the university press released, continue to announce that we have finally shown that "junk DNA" is not actually junk DNA. We've known that for decades now, but every time it is announced as if it was a completely new discovery.

Of course the extent of non-coding DNA that plays some important role has not been known long, and we surely don't understand it yet completely. But finding that some non-coding DNA has a regulatory function has not been a surprise for decades now.

[jonathansizz]

Describing functional non-coding DNA as junk is obviously incorrect, but the fact remains that most non-coding DNA is indeed non-functional, and therefore junk.

[dekhn]

hahahah you're so naive.

can you provide some evidence there is any non-functional DNA in the genome? Try hard, now, you're talking to somebody who's studied this for 20+ years.

[jonathansizz]

Despite your patronizing tone, I fear it may be you who is naive. I don't know what field it is that you've been in for the last 20 years, but I suggest you start reading up on genetics and biochemistry, as you've got a lot of catching up to do. In the meantime, here are a few questions for you to think about.

You are already aware, of course, that 90% of the human genome is unconserved, that 50% of the genome consists of dead transposons and viruses, and that mice have been generated that are homozygous for megabase-scale deletions with no discernible effects? Perhaps you can come up with some hypotheses that could explain these facts that are consistent with your claim of functionality?

You've heard of pseudogenes, right? Why do they look exactly like broken genes? What do they do?

Why is there great variability in the sequences of repetitive DNA in many species, including humans? Why do some individuals have many more copies of these tandem repeats than others? Are the extra repeats functional? If so, why does the number of copies change rapidly and stochastically from generation to generation? Do you know anyone who thinks satellite DNA is functional?

The links below will help you get started on the basics of genome biology. Good luck.

http://www.genomicron.evolverzone.com/2007/04/word-about-jun...

http://sandwalk.blogspot.com/2008/02/theme-genomes-junk-dna....

[dekhn]

Regarding mice, you are likely referring to Eddy Rubin's paper (I familiar of the work in Eddy's team at Berkeley when I was a postdoc in functional genomics in Steven Brenner's lab).

http://www.ncbi.nlm.nih.gov/pubmed/15496924

"Some of the deleted sequences might encode for functions unidentified in our screen; nonetheless, these studies further support the existence of potentially 'disposable DNA' in the genomes of mammals."

Note their qualifications. I'm asking for proof. Making a viable mouse that has a lot of deletions is in no way evidence that the regions are nonfunctional. For example, maybe they deleted a conserved element which has cold-shock response potential, but the mouse was raised in a room temperature environment.

Many of those "worthless transposons" actually seem to play a role in evolution http://www.sciencedirect.com/science/article/pii/S1369526612... and others show that even "dead" transposon probably play a role in the evolution of tail exons: http://genomebiology.com/content/11/6/r59

basically, I know where you're coming from. I used to even believe the dogma. Then I spent some deep time looking at genomes, functional evolution, and biophysics, and came to the conclusion that papers like this: http://www.nature.com/nature/journal/v284/n5757/abs/284604a0... which influenced an entire generation of scientists, are just wrong. Meaningless speculation in the absence of data! Those of us who have spent a lot of time digging into ENCODE and trying to find the really valuable nuggets are starting to come to the conclusion that vast "deserts" of the genome are in fact filled with rich regulatory elements and other functional (including as-yet uncharacterized elements) elements such as RNA genes that classic mechanisms of DNA-evolution-constraint measurement, like Jukes Cantor, are unable to process.

[jonathansizz]

Why won't you answer my questions? It's not up to me to prove a negative, if such a thing were possible.

I wasn't referring to active or co-opted transposons, which make up less than 1% of total transposon sequence in the genome. I'm talking about dead, non-functional transposons. These were indeed active and functional in the distant past, but are long since dead. If you have an hypothesis that such sequences in fact have a function, then by all means let's hear it. Likewise with dead viruses, satellites, etc.

It's interesting you mention 'meaningless speculation in the absence of data', since your friends at ENCODE recently embarrassed themselves in just such a way with their pervasive transcription nonsense, as do those who claim function for repetitive, unconserved regions of the genome without any evidence or even an hypothesis, when we have every reason to believe that these are the remnants of formerly-active elements that were subsequently inactivated.

As I said above, it's clear that a small fraction of non-coding DNA has a regulatory role. We've known about this for decades. Recent discoveries don't account for much; RNA genes make up about 4% of the genome.

Sorry if I've been overly harsh in my replies, but from my experience many bioinformaticians have shown themselves to be ignorant about even basic biology, so I took the precaution of going over a few basics.

[dekhn]

I'm not a bioinformatician. I'm a biophysicist (BS in Molecular Biology and Biochemistry) who works in computer science. That said, as I have worked closely with most of the world's genome experts (and parried with them on this very issue), I am an authority in this area.

Anyway, I don't mind that you're harsh. It's pretty hard for people to unlearn their years of misunderstanding the genome! There is a lot of misinformation. Basically, you're just insisting on this line of reasoning: http://selab.janelia.org/people/eddys/blog/?p=683 "ENCODE says What?"

In regards to the ENCODE project's "embarassment", a couple things happened: 1) the press attributed a number of overly aggressive claims to ENCODE. If you read the papers you'll notice they used very hedged statements. 2) ENCODE actually observed some very interesting things. We took their data, and worked on it some more, and we found that a number of their measured transcription tracks actually did represent functional biology. In particular, I can assure you, based on very solid evidence that your estimate that RNA genes make up only 4% of the genome is vastly lower than reality.

[dekhn]

Would you mind pointing me to a base in the human genome that you claim is non functional. hg19 coords, please.