How Much of Genome is "Functional" or "Neutral"?

[Faizal_Ali]

@Giltil

The connection with ENCODE is the following: in order for a segment of DNA to be fonctional (in the sense of contributing to fitness), it must have some sort of biochemical activity, which seems to be how ENCODE define function. So the discovery by ENCODE that at least 80% of the human genome has some sort of biochemical activity give more credit to the idea that a larger fraction of the human genome than traditionnaly estimated is functional ( in the sense of contributing to fitness)

Not really. I’m not sure that it was a big shock to people who are experienced in genomics that 80% of the genome shows some degree of biochemical activity, according to the extremely loose definition ENCODE used.

[Faizal_Ali]

@John_Harshman

Could you perhaps summarize the relevant points from that presentation?

It appears to be an extended metaphor for the Function Wars, being something that appears to be full of meaning and significance to the uninformed, whereas the better informed realize it is mostly junk.

[glipsnort (Steve Schaffner)]

@Faizal_Ali

Incorrect. If a sequence has a variant (alleles) that is deleterious, it is functional. That applies to all its alleles, whether they are neutral, beneficial, or deleterious.

You are making the same mistake @Ashwin_s is, of confusing “functional” and “beneficial”.

Sorry, but you’re objecting to something I didn’t say. By Graur’s definition, the sequence is functional if any of the possible alleles is deleterious. The function is a capacity that has been shaped by natural selection, i.e. it is a trait conferred by some alleles in that sequence. The function, thus, can be present or absent, depending on what allele is present.

Why you’re trying to make a big deal out of this I have no idea, since my only point was that “capacity shaped by natural selection” and function defined by a physical capacity like eyesight or intelligence may give quite different accounts of what traits are functional.

[glipsnort (Steve Schaffner)]

@Giltil

The connection with ENCODE is the following: in order for a segment of DNA to be fonctional (in the sense of contributing to fitness), it must have some sort of biochemical activity, which seems to be how ENCODE define function. So the discovery by ENCODE that at least 80% of the human genome has some sort of biochemical activity give more credit to the idea that a larger fraction of the human genome than traditionnaly estimated is functional ( in the sense of contributing to fitness)

Why? It’s hardly news that introns, for example, are transcribed, but that’s never been grounds for thinking that they’re mostly functional. I’m aware of no evidence whatsoever that more than 20% of the human genome is functional in this sense. So why does the topic keep coming up? The only reasons I can see are (1), that some ID proponents decided (on what basis I’ve never understood) that a highly functional genome implies intelligent design, and (2) the ENCODE bombast confused a lot of people about what their results actually were.

[T_aquaticus]

@Ashwin_s

No… Graur’s definition is dependent on actual evolutionary history. It has nothing much to do with causal roles except to the extent that some specific functions bare selected for or against.

It might help to put this in a different context. For example, a physicist might say that if Jupiter’s orbit was a perfect square centered around the Sun then the theory of relativity would be wrong. Since Jupiter’s orbit is not a square, the proposition kind of takes care of itself.

[T_aquaticus]

@Faizal_Ali

I’m not sure that it was a big shock to people who are experienced in genomics that 80% of the genome shows some degree of biochemical activity, according to the extremely loose definition ENCODE used.

I wasn’t shocked to learn that junk DNA could be transcribed at very low levels, or that it contained sites where different proteins could bind to it.

[T_aquaticus]

@Giltil

The connection with ENCODE is the following: in order for a segment of DNA to be fonctional (in the sense of contributing to fitness), it must have some sort of biochemical activity, which seems to be how ENCODE define function.

Using that definition, then the trash in your kitchen trash can has function because it can chemically react with the air in your kitchen. A TV that doesn’t produce sound or a picture would be functional because it can bind dust particles. A completely broken down and bullet-hole ridden car would be functional because it can react with the oxygen in the air and produce rust. Does this sound like a useful definition of “functional”? It doesn’t to me. ENCODE confused “does something” with “functional”, plain and simple.

[Faizal_Ali]

@glipsnort

Why you’re trying to make a big deal out of this I have no idea, since my only point was that “capacity shaped by natural selection” and function defined by a physical capacity like eyesight or intelligence may give quite different accounts of what traits are functional.

Yes, and the former is far more accurate, because it does not require one determine the specific function performed by a given sequence, and will more readily identifty non-genic functional sequences.

[glipsnort (Steve Schaffner)]

@Faizal_Ali

Yes, and the former is far more accurate, because it does not require one determine the specific function performed by a given sequence, and will more readily identifty non-genic functional sequences.

That’s not a meaningful statement: the two kinds of function are incommensurable and serve different purposes. If you are trying to develop treatment for impaired vision, you care about what affects the function of vision, not about whether an allele was selected for (except as a means to find the functional alleles you care about). Which is more “accurate” depends on what exactly it is you’re looking for. In practice, the two are often used jointly, as when combining information about conserved elements with the results of a genome-wide association study.

It’s also completely irrelevant to my point so I have no idea why you posted it. Is your goal here simply to find anything at all to disagree about?