[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.