I am curious to know if there is still a debate going on regarding the coverage of human genome (around 80% coding) as concluded by the ENCODE project papers or still we have opponents who believe in the most of our genome as 'junk'?
http://www.nature.com/encode/
As far as I know, results from the ENCODE project do not state that 80% of the human genome is coding DNA (that still seems to be around 2%), but they say it is FUNCTIONAL DNA. Now, this concept of "functional" is what keeps the debate on. If I find a putative binding site for a transcription factor, lets say CACGTG, I can call it a functional DNA region, since there is a function associated to that sequence. However, that would not have biological relevance unless that sequence is found in the context of a promoter and probably associated with other regulatory elements.
I think the main problem is not about the results that were obtained, but how these results were interpreted and presented. Here you can see an interesting opinion on the subject:
http://www.scilogs.com/next_regeneration/the-encode-controversy-and-professionalism-in-science/
As far as I know, results from the ENCODE project do not state that 80% of the human genome is coding DNA (that still seems to be around 2%), but they say it is FUNCTIONAL DNA. Now, this concept of "functional" is what keeps the debate on. If I find a putative binding site for a transcription factor, lets say CACGTG, I can call it a functional DNA region, since there is a function associated to that sequence. However, that would not have biological relevance unless that sequence is found in the context of a promoter and probably associated with other regulatory elements.
I think the main problem is not about the results that were obtained, but how these results were interpreted and presented. Here you can see an interesting opinion on the subject:
http://www.scilogs.com/next_regeneration/the-encode-controversy-and-professionalism-in-science/
I think you guys are missing some of the findings. ENCODE is not just saying 80% is functional, they're saying 80% is transcribed:
http://www.nature.com/nature/journal/v489/n7414/full/nature11233.html
There is controversy about whether these transcripts produce polypeptides, however the non coding RNA does bind ribosomes at the same frequency as mRNA:
http://www.cell.com/abstract/S0092-8674(13)00711-3
I think this work shows how powerful RNA-seq is, and how far off the central dogma actually is.
I think that genome context is important when discussing function. Regulatory elements may only function as such when in the correct genomic context (i.e. upstream of a gene). However, I think the ENCODE results provide an important catalogue of DNA regions that maybe functional and can be very useful to each researcher studying their favourite pathway or gene (giving context to the results). Another thing to consider is the definition of the term "functional". This is addressed in a strongly worded commentary by Graur et al 2013 (Genome Biol Evol (2013) doi: 10.1093/gbe/evt028).
Few people believe that most of the genome is junk. It is likely to have critical regulatory and/or structural functions. However, the ENCODE project does not really solve the issue. Whether any specific peaks of histone methylation or TF binding sites are really functional will still need to be tested. There is a tremendous amount of noise in biological systems, the real key will be distinguishing the noise from the critical regulatory pathways.
I agree that the key issue about ENCODE findings is the term "functional" and there will surely be many more debates over this term. However, it is interesting that Graur et al (2013) insist on the evolutionary aspect of determining functionality of parts of the genome, whilst forgetting to take an evolutianary view themselves. Namely, whilst some DNA elements may not be currently functional (part of a pathway etc) they could serve as a reservoir of elements for the species. So they wouldn't be under purifying selection at this moment in time, but provided they avoid the decay of time, could be under purifying selection later on in the existence of the species (or genus). A simple example would be duplication of a gene - witnessed in evolution of countless traits. It would take many more steps for various traits to evolve if there were no diverse DNA elements on "stand-by" present in the genome. Are there any evolutionary biologists out there that could give me their opinion on this?
After reading Graur et al (2013) more carefully I have to correct myself: they did mention that parts of DNA that are currently non-functional could be useful for the species later - they call this "future potential" and assign this role to 'junk' DNA (as opposed to 'garbage' DNA). Sneering and belittling comments asside (how did those get published!?), they raise some very good points about the experimental systems ENCODE used, their data analysis and conclusions. Abbas, I think the debate continues..
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