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URL:  http://boards.fool.com/read-farther-brian-the-next-phase-is-to-find-out-30263448.aspx

Subject:  Re: 100% function, take THAT junk theory Date:  9/14/2012  5:53 PM
Author:  adonsant Number:  23922 of 24926

Read farther, Brian!

The next phase is to find out how these players interact with one another. What does the 80 percent do (if, genuinely, anything)? If it does something, does it do something important? Does it change something tangible, like a part of our body, or our risk of disease? If it changes, does evolution care?

[Update 07/09 23:00 Indeed, to many scientists, these are the questions that matter, and ones that ENCODE has dodged through a liberal definition of “functional”. That, say the critics, critically weakens its claims of having found a genome rife with activity. Most of the ENCODE’s “functional elements” are little more than sequences being transcribed to RNA, with little heed to their physiological or evolutionary importance. These include repetitive remains of genetic parasites that have copied themselves ad infinitum, the corpses of dead and once-useful genes, and more.


And later:

He expects that many skeptics will argue about the 80 percent figure, and the definition of “functional”. But he says, “No matter how you cut it, we’ve got to get used to the fact that there’s a lot more going on with the genome than we knew.”

[Update 07/09 23:00 Birney was right about the scepticism. Gregory says, “80 percent is the figure only if your definition is so loose as to be all but meaningless.” Larry Moran from the University of Toronto adds, “Functional" simply means a little bit of DNA that's been identified in an assay of some sort or another. That’s a remarkably silly definition of function and if you're using it to discount junk DNA it's downright disingenuous.”

This is the main criticism of ENCODE thus far, repeated across many blogs and touched on in the opening section of this post. There are other concerns. For example, White notes that many DNA-binding proteins recognise short sequences that crop up all over the genome just by chance. The upshot is that you’d expect many of the elements that ENCODE identified if you just wrote out a random string of As, Gs, Cs, and Ts. “I've spent the summer testing a lot of random DNA,” he tweeted. “It’s not hard to make it do something biochemically interesting.”


To make an analogy, consider a car with no transmission and no brakes. If you sit it on a level surface, it doesn't move. But, if you sit it on the deck of a ship at sea, it rolls all over. By ENCODE's definition of "function", the car classifies as functional. I think most of us would that to be stretching the concept of functional to its breaking point.

That's not to say that the data generated by the ENCODE project are useless. I think they will probably be very valuable to molecular biologists trying to understand the nitty-gritty of gene regulation and identifying truly functional non-coding RNAs. But they're a long way from determining which sequences have an honest-to-goodness function and those that can be done away with without any quantifiable effect.

-Anthony
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