Junk DNA is still junk

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Blogging on Peer-Reviewed Research

The ENCODE project made a big splash a couple of years ago — it is a huge project to not only ask what the sequence of a strand of human DNA was, but to analyzed and annotate and try to figure out what it was doing. One of the very surprising results was that in the sections of DNA analyzed, almost all of the DNA was transcribed into RNA, which sent the creationists and the popular press into unwarranted flutters of excitement that maybe all that junk DNA wasn't junk at all, if enzymes were busy copying it into RNA. This was an erroneous assumption; as John Timmer pointed out, the genome is a noisy place, and coupled with the observations that the transcripts were not evolutionarily conserved, it suggested that these were non-functional transcripts.

Personally, I fall into the "it's all junk" end of the spectrum. If almost all of these sequences are not conserved by evolution, and we haven't found a function for any of them yet, it's hard to see how the "none of it's junk" view can be maintained. There's also an absence of support for the intervening view, again because of a lack of evidence for actual utility. The genomes of closely related species have revealed very few genes added from non-coding DNA, and all of the structural RNA we've found has very specific sequence requirements. The all-junk view, in contrast, is consistent with current data.

Larry Moran was dubious, too — the transcripts could easily by artifactual.

The most widely publicized result is that most of the human genome is transcribed. It might be more correct to say that the ENCODE Project detected RNA's that are either complimentary to much of the human genome or lead to the inference that much of it is transcribed.

This is not news. We've known about this kind of data for 15 years and it's one of the reasons why many scientists over-estimated the number of humans genes in the decade leading up to the publication of the human genome sequence. The importance of the ENCODE project is that a significant fraction of the human genome has been analyzed in detail (1%) and that the group made some serious attempts to find out whether the transcripts really represent functional RNAs.

My initial impression is that they have failed to demonstrate that the rare transcripts of junk DNA are anything other than artifacts or accidents. It's still an open question as far as I'm concerned.

I felt the same way. ENCODE was spitting up an anomalous result, one that didn't fit with any of the other data about junk DNA. I suspected a technical artifact, or an inability of the methods used to properly categorize low frequency accidental transcription in the genome.

Creationists thought it was wonderful. They detest the idea of junk DNA — that the gods would scatter wasteful garbage throughout our precious genome by intent was unthinkable, so any hint that it might actually do something useful is enthusiastically siezed upon as evidence of purposeful design.

Well, score one for the more cautious scientists, and give the creationists another big fat zero (I think the score is somewhere in the neighborhood of a big number requiring scientific notation to be expressed for the scientists, against a nice, clean, simple zero for the creationists). A new paper has come out that analyzes transcripts from the human genome using a new technique, and, uh-oh, it looks like most of the early reports of ubiquitous transcription were wrong.

Here's the author's summary:

The human genome was sequenced a decade ago, but its exact gene composition remains a subject of debate. The number of protein-coding genes is much lower than initially expected, and the number of distinct transcripts is much larger than the number of protein-coding genes. Moreover, the proportion of the genome that is transcribed in any given cell type remains an open question: results from "tiling" microarray analyses suggest that transcription is pervasive and that most of the genome is transcribed, whereas new deep sequencing-based methods suggest that most transcripts originate from known genes. We have addressed this discrepancy by comparing samples from the same tissues using both technologies. Our analyses indicate that RNA sequencing appears more reliable for transcripts with low expression levels, that most transcripts correspond to known genes or are near known genes, and that many transcripts may represent new exons or aberrant products of the transcription process. We also identify several thousand small transcripts that map outside known genes; their sequences are often conserved and are often encoded in regions of open chromatin. We propose that most of these transcripts may be by-products of the activity of enhancers, which associate with promoters as part of their role as long-range gene regulatory sites. Overall, however, we find that most of the genome is not appreciably transcribed.

So, basically, they directly compared the technique used in the ENCODE analysis (the "tiling" microarray analysis) to more modern deep sequencing methods, and found that the old results were mostly artifacts of the protocol. They also directly examined the pool of transcripts produced in specific tissues, and asked what proportion of them came from known genes, and what part came from what has been called the "dark matter" of the genome, or what has usually been called junk DNA. The cell's machinery to transcribe genes turns out to be reasonably precise!

To assess the proportion of unique sequence-mapping reads accounted for by dark matter transcripts in RNA-Seq data, we compared the mapped sequencing data to the combined set of known gene annotations from the three major genome databases (UCSC, NCBI, and ENSEMBL, together referred to here as "annotated" or "known" genes). When considering uniquely mapped reads in all human and mouse samples, the vast majority of reads (88%) originate from exonic regions of known genes. These figures are consistent with previously reported fractions of exonic reads of between 75% and 96% for unique reads, including those of the original studies from which some of the RNA-Seq data in this study were derived. When including introns, as much as 92%-93% of all reads can be accounted for by annotated gene regions. A further 4%-5% of reads map to unannotated genomic regions that can be aligned to spliced ESTs and mRNAs from high-throughput cDNA sequencing efforts, and only 2.2%-2.5% of reads cannot be explained by any of the aforementioned categories.

Furthermore, when they looked at where the mysterious transcripts are coming from, they are most frequently from regions of DNA near known genes, not just out of deep intergenic regions. This also suggests that they're an artifact, like an extended transcription of a gene, or from other possibly regulatory bits, like pasRNA (promoter-associated small RNAs — there's a growing cloud of xxxRNA acronyms growing out there, but while they may be extremely useful, like siRNA, they're still tiny as a fraction of the total genome. Don't look for demolition of the concept of junk DNA here).

There clearly are still mysteries in there — they do identify a few novel transcripts that come up out of the intergenic regions — but they are small and rare, and the fact of their existence does not imply a functional role, since they could simply be byproducts of other processes. The only way to demonstrate that they actually do something will require experiments in genetic perturbation.

The bottom line, though, is the genome is mostly dead, transcriptionally. The junk is still junk.


van Bakel H, Nislow C, Blencowe BJ, Hughes TR (2010) Most "Dark Matter" Transcripts Are Associated With Known Genes. PLoS Biology 8(5):1-21.

186 Comments

Interesting, a good summary.

Opponents of evolutionary biology are always saying that “Intelligent Design predicts that there is no junk DNA”. They also say that ID is not religion but a straightforward scientific theory. Now I can think of theological arguments against the existence of junk DNA (along the lines of “No self-respecting Deity would …”).

But if we rule out that theological argument, exactly where in ID do this supposed “prediction” come from? I don’t recall anything in the writings of Dembski or Behe that makes any such prediction. Does anyone have a non-theology source for it?

Joe Felsenstein said:

Interesting, a good summary.

Opponents of evolutionary biology are always saying that “Intelligent Design predicts that there is no junk DNA”. They also say that ID is not religion but a straightforward scientific theory. Now I can think of theological arguments against the existence of junk DNA (along the lines of “No self-respecting Deity would …”).

But if we rule out that theological argument, exactly where in ID do this supposed “prediction” come from? I don’t recall anything in the writings of Dembski or Behe that makes any such prediction. Does anyone have a non-theology source for it?

Lemme pull an ID bait and switch on you here simply to answer your question:

“…along the lines of “No self-respecting Deity Intelligent Designer would…”

This only has any meaning if we know something about the Intelligent Designer. Since, for the ID folks, it is already known a priori that the designer is God and we are made in his image, it all fits in nicely with their little framework.

Does anyone have a non-theology source for it?

Since ID’ers are quick to say there is no reason to expect optimal designs, I believe the motivation for the prediction is “functionality would show scientists have been wrong, so ID must be right.” Pretty much the stock ID negative argument, posing for the rubes as a positive hypothesis.

As far back as around 2000, Johnny Wells and S. Meyer were predicting DNA will almost all be functional. Here’s poodle Casey Luskin summarizing ID predictions. Note the last prediction and footnote 6 – apparently this falsifies ID once and for all. Cough.

How can ID predict that there is no junk DNA? Such a prediction can only be made with the assumption of a design that minimizes genomic waste. But that assumption is based on speculation on the nature of the designer. And that’s a non-no, or so the IDers keep telling us.

Genomic waste? What fraction of a cell’s mass is its DNA? If the mass of the DNA is tiny compared to the whole cell, and doesn’t require excessive amount of resources to produce and maintain it, then where’s the waste?

Henry J said:

Genomic waste? What fraction of a cell’s mass is its DNA? If the mass of the DNA is tiny compared to the whole cell, and doesn’t require excessive amount of resources to produce and maintain it, then where’s the waste?

I was talking about DNA over and above that which is needed.

What I’m wondering is how the cost of having the unused DNA compares to the total cost of running the cell. That seems to me to be more important than comparing the cost of the junk DNA to the cost of the functional DNA.

JohnK said:

Does anyone have a non-theology source for it?

Since ID’ers are quick to say there is no reason to expect optimal designs, I believe the motivation for the prediction is “functionality would show scientists have been wrong, so ID must be right.” Pretty much the stock ID negative argument, posing for the rubes as a positive hypothesis.

As far back as around 2000, Johnny Wells and S. Meyer were predicting DNA will almost all be functional. Here’s poodle Casey Luskin summarizing ID predictions. Note the last prediction and footnote 6 – apparently this falsifies ID once and for all. Cough.

Well, item one of Table 2. is also a prediction of evolution, and therefore useless for distinguishing between the two. Items 2,3, and 4 have been falsified. I hope someone far more literate and renowned will publically put Wells in his place, again.

Aha! ID has always predicted that there would be loads of junk DNA, because the human genome has been degrading ever since the Fall, uh, I mean, since the designer designed us! And we’ve always been at war with Eastasia!

Aagcobb said:

Aha! ID has always predicted that there would be loads of junk DNA, because the human genome has been degrading ever since the Fall, uh, I mean, since the designer designed us! And we’ve always been at war with Eastasia!

Y’know, every time creationists go into this “Designer builds things up evolution tears them down” routine I wonder just why the Designer didn’t design out evolution.

But maybe that’s being badthinkful.

It doesn’t get any better than this!

weren’t you banned from here eons ago, John?

do you truly love it so?

aren’t you having enough fun arguing with yourself on any of your own blogs?

Well,

johnadavison said:

Neo-Darwinism is as dead as the proverbial doornail. It has become perfectly obvious that phylogeny was planned from beginning to end and the end is any time now.

Didn’t you see the news reports? It happened last week. It should have been on the obit page.

What I’m wondering is how the cost of having the unused DNA compares to the total cost of running the cell. That seems to me to be more important than comparing the cost of the junk DNA to the cost of the functional DNA.

The energetic cost of extra DNA is pretty tiny for your typical eukaryotic cell, apparently, although I can’t find any actual calculations on this topic. One textbook, though, says:

“The energy invested in DNA synthesis is trivial compared with the metabolic energy required for the movement of muscles; thus there was little selective pressure to eliminate nonfunctional DNA in vertebrates.” (Lodish et al. 2003)

…although there might be such pressure in some single-celled organisms.

Junk DNA is “wasteful”, though, if you think of the genome like you would think of a book, like ID advocates do. The genome would be a book that was 75%+ full of gibberish or short repetitive sequence.

I once saw a comment someplace that large genomes tend to be correlated with large cells, and that cell size may have selective advantages.

So junk DNA may actually have a function, just as wadded-up pages of newspapers used for packing something fragile in a box have a function. In either case, it’s not there to be read.

The genome would be a book that was 75%+ full of gibberish or short repetitive sequence.

heh, I often think most books are.

the end is any time now.

wait, how old are you again, John?

JohnK said:

Since ID’ers are quick to say there is no reason to expect optimal designs,

That’s only when someone is pointing out the lack of optimal design. Then when nobody is looking any more, then they can go back to expecting optimal design again. Depends on what day it is I guess. (And how many gaps in knowledge there are of course.) Classic god-of-the-gaps. Classic denialist hypocrisy.

MrG said:

I once saw a comment someplace that large genomes tend to be correlated with large cells, and that cell size may have selective advantages.

e.g. “Origin of avian genome size and structure in non-avian dinosaurs,” Organ et al., Nature v 446 p 180 (8 March 2007)

And before that, Masterson, J. 1994. Stomatal Size in Fossil Plants: Evidence for Polyploidy in Majority of Angiosperms. Science 264:421-424.

Abstract: Three published estimates of the frequency of polyploidy in angiosperms (30 to 35 percent, 47 percent, and 70 to 80 percent) were tested by estimating the genome size of extinct woody angiosperms with the use of fossil guard cell size as a proxy for cellular DNA content. The inferred chromosome numbers of these extinct species suggest that seven to nine is the primitive haploid chromosome number of angiosperms and that most angiosperms (approximately 70 percent) have polyploidy in their history.

Ichthyic said:

the end is any time now.

wait, how old are you again, John?

Let’s just say that, when John was first learning kungfu, Jack Benny was celebrating his 38th birthday.

I wonder if the nonfunctional DNA increases the amount of space per useful gene, which might reduce the amount of delays due to DNA readers getting in each others way?

Henry

The bottom line, though, is the genome is mostly dead, transcriptionally. The junk is still junk.

This statement assumes that DNA is only functional if it is transcribed.

johnadavison said:

I thank Wes or Pee Zee or whoever is responsible for allowing me once again to opine here. I am disappointed that Ichthyic had to stoop to refer to my age. Since he asked, I will be 82 on June 25 next. Let me quote one of my contemporaries.

“You ain’t heard nothin’ yet.” Al Jolson

I have a book coming out soon which is a collection of my unpublished papers and essays dealing with the great mystery of phylogeny. I expect it to be reviewed here.

In the meantime I recommend the following link -

http://jadavison.wordpress.com/2008[…]ns/#comments

For a sample of what to expect, especially #249 and several preceding messages.

Wow! You are even more insane and incompetent than I’d heard! Why have you never learned how to manage a blog properly?

kakapo said:

MrG said:

I once saw a comment someplace that large genomes tend to be correlated with large cells, and that cell size may have selective advantages.

e.g. “Origin of avian genome size and structure in non-avian dinosaurs,” Organ et al., Nature v 446 p 180 (8 March 2007)

You may look for the “Flying DNA Hypothesis”.

Intelligent Designer said:

This statement assumes that DNA is only functional if it is transcribed.

And how else would DNA have a function?

This statement assumes that DNA is only functional if it is transcribed.

Eliminating transcription greatly narrows down the functional possibilities.

Junk DNA is “wasteful”, though, if you think of the genome like you would think of a book, like ID advocates do. The genome would be a book that was 75%+ full of gibberish or short repetitive sequence.

LOL read an ID book lately?

Indeed this provides the rational for reversing the prediction to “ID predicts lots of junk DNA”, since they consider themselves intelligent designers.

johnadavison said:

I see I was not allowed to respond to Dale Husband’s vicious attack on my integrity and sanity. My lengthy response was deleted after its brief appearance. That has become a trademark of Panda’s Thumb policy of intolerant protectionism and intellectual bigotry. Let’s see if this will be allowed to stand.

You’re getting PT confused with creationist blogs again. I’ll give you clue which is which - one isn’t based on a single information source that is claimed to have come from a superior being.

Onto subject matter: I’m always wary about anything science-y saying that something isn’t needed, or is ‘junk’. It’s better to hedge such statements with a proviso that it’s junk according to current theories. Otherwise, by making such absolutes, there is the risk that at somepoint in the future, a function may be found (even it’s only for cell packing), and the cDesignists will have something to wave around and assume it proves something.

One of the big divisions between informed scientific opinion and dogmatic creationist rantings is the ability of science to never hold to absolutes, to always be willing to change and adapt if a better and more plausible idea is put forwards.

Dave Wisker said:

This statement assumes that DNA is only functional if it is transcribed.

Eliminating transcription greatly narrows down the functional possibilities.

One postulate (the current status of which I don’t know) is that “excess” non-transcribed DNA provides a buffer against ionizing radiation by keeping the resulting coding region mutation frequency low.

OgreMkV -

This statement assumes that DNA is only functional if it is transcribed.

And how else would DNA have a function?

It is not known, and depends on what one means by “function”. Also, DNA which is transcribed into RNA which is immediately degraded could have no positive “function” except to consume energy, whereas DNA that is usually not transcribed might have some sort of structural function, or be transcribed in a manner that is so novel or rare that we don’t recognize it yet.

But the data support neither the ludicrous and dishonest claims of creationists (of course), nor the oversimplification “since a creationist said it should have a function and since we colloquially call it ‘junk’, therefore it must have no function or activity whatsoever”.

In fact, mice lacking large regions of junk DNA are a major model in ongoing research.

Such mice are perfectly viable at birth, ruling out the idea that the deleted DNA performs a function necessary for life.

But they also differ from other mice in important, if subtle, ways.

http://www.nih.gov/researchmatters/[…]010heart.htm

Creationist arguments are literally almost always wrong, but it does not follow that “the exact opposite” of a creationist argument is always right.

PZ Myers said:

Inventing a new pseudoscientific term for a phenomenon which has no empirical evidence for its existence except for a brief mention on your dismally malinformative blog is not a rationale, Mr Stimpson.

Stimpson’s blog post refers to a post you made on Pharyngula about a paper on lizard evolution by Herrel et al. Do you know if the investigators ever followed up with a comparison of the full genomes of the two strains of P. sicula? It would be interesting to know how much genetic change actually occurred, and which genes were affected.

Intelligent Designer said:

PZ Myers said:

Inventing a new pseudoscientific term for a phenomenon which has no empirical evidence for its existence except for a brief mention on your dismally malinformative blog is not a rationale, Mr Stimpson.

I didn’t exactly invent the term. I just choose more neutral term for term “evolutionary capacitance” used extensively by Jerry Coyne in “Why Evolution is True”. You will also find that Wikipedia, perhaps incorrectly, states that “evolutionary capacitance” is a biological theory.

Jerry Coyne presents it as evidence for evolution. I think it is evidence for intelligent design.

Also your own blog presents evidence for the hypothesis here.

“Evolutionary capacitance” … you keep using that term. I do not think it means what you think it means.

You might want to check out the original paper by Bergman and Siegel where it’s defined.

SWT said:

“Evolutionary capacitance” … you keep using that term. I do not think it means what you think it means.

You might want to check out the original paper by Bergman and Siegel where it’s defined.

The paper you sited provides more specific details but I don’t see anything in it contrary to what I have stated.

Intelligent Designer said:

SWT said:

“Evolutionary capacitance” … you keep using that term. I do not think it means what you think it means.

You might want to check out the original paper by Bergman and Siegel where it’s defined.

The paper you sited provides more specific details but I don’t see anything in it contrary to what I have stated.

The paper I cited showed that evolutionary capacitance can be a natural consequence of the evolutionary process and has nothing to do with non-transcribed DNA. It is in no way evidence for intelligent design.

I’m late to this party, but I’ve been puzzled at the apparent controversy over so-called Junk DNA.

Imagine a world in which the evolutionary hypothesis is true. As evolution progresses, one would *expect* the process to be messy and leave behind nonfunctional pieces. Nobody would expect the process of evolution to ‘clean up’ after itself. Would we? Unless there were an evolutionary advantage to doing so, and it seems more likely there would be lots of ‘junk’ lying around that had a purpose when it started and no long does.

A billion years of evolution, a billion years of evolutionary trash left behind - not only is that not surprising, it would be mighty surprising if it were any other way. It seems to me inevitable that some features of the genome will be nonfunctional left-behinds. So what’s the big deal?

That’s exactly right - as I understand it, there is no big deal scientifically, and you’re probably right that there would be if there wasn’t a lot of junk. (Although I do recall that the prevalence of junk wasn’t predicted ahead of time.)

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