Junk & Jonathan: Part 11—Chapter 8

This is part 11 of my review of The Myth of Junk DNA. For a list of other postings on this topic see the links in Genomes & Junk DNA in the "theme box" below or in the sidebar under "Themes."

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The title of Chapter 8 is "Some Recent Defenders of Junk DNA." It is Wells' attempt to deal with a very small percentage of the criticisms of his claim.

He begins with a reference to a 2003 paper that reported on transcription of a pseudogene and proposed a function for that transcript. He then references a 2006 paper that refutes the earlier study showing that the pseudogene transcript has no function. Good for Wells. That means he is aware of the fact that some of the work he references has not been reproduced. It's bizarre that Wells devotes three paragraphs to the discredited reference in Junk & Jonathan: Part 7—Chapter 4 and only mentions in passing that the result has been challenged.

He returns to this result in Chapter 8 and all but admits that the original result—so prominently presented in Chapter 3—is no longer valid. However, Wells can't leave it at that. The 2006 paper by Gray et al. went on to point out that some creationist literature had written up the earlier incorrect result and claimed that this was support for functional "junk DNA" and support for intelligent design creationism. The authors conclude their paper with ...

Furthermore, because Mkrn1-p1 is a nonfunctional pseudogene and does not trans-regulate its source Mkrn1 gene as claimed (6–9), our work reestablishes the evolutionary paradigm supported by overwhelming evidence that mammalian pseudogenes are indeed inactive gene relics.

Answering Barry Arrington's challenge: Darwinism predicted junk DNA

In my first post [Answering Barry Arrington's challenge: Darwinism] I established that Barry Arrington's version of "Darwinism" is actually "Neo-Darwinism" or the "Modern Synthesis." We all know why Intelligent Design Creationists would rather use "Darwinism"—this explains why they deliberately change the meaning to make it look like they understand evolution

Arrington's version of "Darwinism can be seen in the Uncommon Descent glossary. It focuses on natural selection as the mechanism of evolution and doesn't mention Neutral Theory of random genetic drift.

Barry Arrington's challenge to me is ...

The Function Wars: Part II

This is Part II of several "Function Wars"¹ posts. The first one is on Quibbling about the meaning of the word "function" [The Function Wars: Part I].

The ENCODE legacy

I addressed the meaning of "function" in Part I It is apparent that philosophers and scientists are a long way from agreeing on an acceptable definition. There has been a mini-explosion of papers on this topic in the past few years, stimulated by the ENCODE Consortium publicity campaign where the ENCODE leaders clearly picked a silly definition of "function" in order to attract attention.

Unfortunately, the responses to this mistake have not clarified the issue at all. Indeed, some philosophers have even defended the ENCODE Consortium definition (Germain et al., 2014). Some have opposed the ENCODE definition but come under attack from other scientists and philosophers for using the wrong definition (see Elliott et al, 2014). The net effect has been to lend credence to the ENCODE Consortium’s definition, if only because it becomes one of many viable alternatives.

Copilot answers the question, "What is junk DNA?"

The Microsoft browser (Edge) has a built in function called Copilot. It's an AI assistant based on ChatGPT-4.

I decided to test it byt asking "What is junk DNA?" and here's the answer it gave me.

Nils Walter disputes junk DNA: (5) What does the number of transcripts per cell tell us about function?

I'm discussing a recent paper published by Nils Walter (Walter, 2024). He is arguing against junk DNA by claiming that the human genome contains large numbers of non-coding genes.

This is the fifth post in the series. The first one outlines the issues that led to the current paper and the second one describes Walter's view of a paradigm shift. The third post describes the differing views on how to define key terms such as 'gene' and 'function.' The fourth post makes the case that differing views on junk DNA are mainly due to philosophical disagreements.

-Nils Walter disputes junk DNA: (1) The surprise

-Nils Walter disputes junk DNA: (2) The paradigm shaft

-Nils Walter disputes junk DNA: (3) Defining 'gene' and 'function'

-Nils Walter disputes junk DNA: (4) Different views of non-functional transcripts

Transcripts vs junk DNA

The most important issue, according to Nils Walter, is whether the human genome contains huge numbers of genes for lncRNAs and other types of regulatory RNAs. He doesn't give us any indication of how many of these potential genes he thinks exist or what percentage of the genome they cover. This is important since he's arguing against junk DNA but we don't know how much junk he's willing to accept.

There are several hundred thousand transcripts in the RNA databases. Most of them are identified as lncRNAs because they are bigger than 200 bp. Let's assume, for the sake of argument, that 200,000 of these transcripts have a biologically relevant function and therefore there are 200,000 non-coding genes. A typical size might be 1000 bp so these genes would take up about 6.5% of the genome. That's about 10 times the number of protein-coding genes and more than 6 times the amount of coding DNA.

That's not going to make much of a difference in the junk DNA debate since proponents of junk DNA argue that 90% of the genome is junk and 10% is functional. All of those non-coding genes can be accommodated within the 10%.

The ENCODE researchers made a big deal out of pervasive transcription back in 2007 and again in 2012. We can quibble about the exact numbers but let's say that 80% of the human is transcribed. We know that protein-coding genes occupy at least 40% percent of the genome so much of this pervasive transcription is introns. If all of the presumptive regulatory genes are located in the remaining 40% (i.e. none in introns), and the average size is 1000 bp, then this could be about 1.24 million non-coding genes. Is this reasonable? Is this what Nils Walter is proposing?

I think there's some confusion about the difference between large numbers of functional transcripts and the bigger picture of how much total junk DNA there is in the human genome. I wish the opponents of junk DNA would commit to how much of the genome they think is functional and what evidence they have to support that position.

But they don't. So instead we're stuck with debates about how to decide whether some transcripts are functional or junk.

What does transcript concentration tell us about function?

If most detectable transcripts are due to spurious transcription of junk DNA then you would expect these transcripts to be present at very low levels. This turns out to be true as Nils Walter admits. He notes that "fewer than 1000 lncRNAs are present at greater than one copy per cell."

This is a problem for those who advocate that many of these low abundance transcripts must be functional. We are familiar with several of the ad hoc hypotheses that have been advanced to get around this problem. John Mattick has been promoting them for years [John Mattick's new paradigm shaft].

Walter advances two of these excuses. First, he says that a critical RNA may be present at an average of one molecule per cell but it might be abundant in just one specialized cell in the tissue. Furthermore, their expression might be transient so they can only be detected at certain times during development and we might not have assayed cells at the right time. I assume he's advocating that there might be a short burst of a large number of these extremely specialized regulatory RNAs in these special cells.

As far as I know, there aren't many examples of such specialized gene expression. You would need at least 100,000 examples in order to make a viable case for function.

His second argument is that many regulatory RNAs are restricted to the nucleus where they only need to bind to one regulatory sequence to carry out their function. This ignores the mass action laws that govern such interactions. If you apply the same reasoning to proteins then you would only need one lac repressor protein to shut down the lac operon in E. coli but we've known for 50 years that this doesn't work in spite of the fact that the lac repressor association constant shows that it is one of the tightest binding proteins known [DNA Binding Proteins]. This is covered in my biochemistry textbook on pages 650-651.¹

If you apply the same reasoning to mammalian regulatory proteins then it turns out that you need 10,000 transcription factor molecules per nucleus in order to ensure that a few specific sites are occupied. That's not only because of the chemistry of binary interactions but also because the human genome is full of spurious sites that resemble the target regulatory sequence [The Specificity of DNA Binding Proteins]. I cover this in my book in Chapter 8: "Noncoding Genes and Junk RNA" in the section titled "On the important properties of DNA-binding proteins" (pp. 200-204). I use the estrogen receptor as an example based on calculations that were done in the mid-1970s. The same principles apply to regulatory RNAs.

This is a disagreement based entirely on biochemistry and molecular biology. There aren't enough examples (evidence) to make the first argument convincing and the second argument makes no sense in light of what we know about the interactions between molecules inside of the cell (or nucleus).

Note: I can almost excuse the fact that Nils Walter ignores my book on junk DNA, my biochemistry textbook, and my blog posts, but I can't excuse the fact that his main arguments have been challenged repeatedly in the scientific literature. A good scientist should go out of their way to seek out objections to their views and address them directly.

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1. In addition to the thermodynamic (equilibrium) problem, there's a kinetic problem. DNA binding proteins can find their binding sites relatively quickly by one dimensional diffusion—an option that's not readily available to regulatory RNAs [Slip Slidin' Along - How DNA Binding Proteins Find Their Target].

Walter, N.G. (2024) Are non‐protein coding RNAs junk or treasure? An attempt to explain and reconcile opposing viewpoints of whether the human genome is mostly transcribed into non‐functional or functional RNAs. BioEssays:2300201. [doi: 10.1002/bies.202300201]

The Function Wars: Part I

This is Part I of the "Function Wars: posts. The second one is on The ENCODE legacy.¹

Quibbling about the meaning of the word "function"

The world is not inhabited exclusively by fools and when a subject arouses intense interest and debate, as this one has, something other than semantics is usually at stake.
Stephan Jay Gould (1982)The ENCODE Consortium tried to redefine the word “function” to include any biological activity that they could detect using their genome-wide assays. This was not helpful since it included a huge number of sites and sequences that result from spurious (nonfunctional) binding of transcription factors or accidental transcription of random DNA sequences to make junk RNA [see What did the ENCODE Consortium say in 2012?]..

I believe that this strange way of redefining biological function was a deliberate attempt to discredit junk DNA. It was quite successful since much of the popular press interpreted the ENCODE results as refuting or disproving junk DNA. I believe that the leaders of the ENCODE Consortium knew what they were doing when they decided to hype their results by announcing that 80% of the human genome is functional [see The Story of You: Encode and the human genome – video, Science Writes Eulogy for Junk DNA]..

The ENCODE Project, today, announces that most of what was previously considered as 'junk DNA' in the human genome is actually functional. The ENCODE Project has found that 80 per cent of the human genome sequence is linked to biological function.

[Google Earth of Biomedical Research]

Nils Walter disputes junk DNA: (6) The C-value paradox

I'm discussing a recent paper published by Nils Walter (Walter, 2024). He is arguing against junk DNA by claiming that the human genome contains large numbers of non-coding genes.

This is the fifth post in the series. The first one outlines the issues that led to the current paper and the second one describes Walter's view of a paradigm shift/shaft. The third post describes the differing views on how to define key terms such as 'gene' and 'function.' In the fourth post I discuss his claim that differing opinions on junk DNA are mainly due to philosophical disagreements.

• Nils Walter disputes junk DNA: (1) The surprise
• Nils Walter disputes junk DNA: (2) The paradigm shaft
• Nils Walter disputes junk DNA: (3) Defining 'gene' and 'function'
• Nils Walter disputes junk DNA: (4) Different views of non-functional transcripts
• Nils Walter disputes junk DNA: (5) What does the number of transcripts per cell tell us about function?

The function wars are over

In order to have a productive discussion about junk DNA we needed to agree on how to define "function" and "junk." Disagreements over the definitions spawned the Function Wars that became intense over the past decade. That war is over and now it's time to move beyond nitpicking about terminology.

The idea that most of the human genome is composed of junk DNA arose gradually in the late 1960s and early 1970s. The concept was based on a lot of evidence dating back to the 1940s and it gained support with the discovery of massive amounts of repetitive DNA.

Various classes of functional DNA were known back then including: regulatory sequences, protein-coding genes, noncoding genes, centromeres, and origins of replication. Other categories have been added since then but the total amount of functional DNA was not thought to be more than 10% of the genome. This was confirmed with the publication of the human genome sequence.

From the very beginning, the distinction between functional DNA and junk DNA was based on evolutionary principles. Functional DNA was the product of natural selection and junk DNA was not constrained by selection. The genetic load argument was a key feature of Susumu Ohno's conclusion that 90% of our genome is junk (Ohno, 1972a; Ohno, 1972b).

Junk & Jonathan: Part 2— What Did Biologists Really Say About Junk DNA?

This is the second in a series of postings about a new book by Jonathan Wells: The Myth of Junk DNA. The book is published by Discovery Institute Press and it should go on sale on May 31 2011. I'm responding to an interview with Jonathan Wells on Uncommon Descent [Jonathan Wells on his book, The Myth of Junk DNA – yes, it is a Darwinist myth and he nails it as such].

Denyse O'Leary asks, "Interestingly, in the “nail dump is Ming vase” story, no one insists that nobody ever thought it was just another piece of junk. They almost always say, “Yes, we thought so but had no idea …” So what’s behind the failure to admit an error in this case?" It's hard to figure out what she means but I think she's wondering why biologists don't just admit they were wrong about junk DNA. Jonathan Wells interprets the question differently.

Some people revise history by claiming that no mainstream biologists ever regarded non-protein-coding DNA as “junk.”

This claim is easily disproved: Francis Crick and Leslie Orgel published an article in Nature in 1980 (284: 604-607) arguing that such DNA “is little better than junk,” and “it would be folly in such cases to hunt obsessively” for functions in it. Since then, Brown University biologist Kenneth R. Miller, Oxford University biologist Richard Dawkins, University of Chicago biologist Jerry A. Coyne, and University of California–Irvine biologist John C. Avise have all argued that most of our DNA is junk, and that this provides evidence for Darwinian evolution and against intelligent design. National Institutes of Health director Francis Collins argued similarly in his widely read 2006 book The Language of God.

It is true that some biologists (such as Thomas Cavalier-Smith and Gabriel Dover) have long been skeptical of “junk DNA” claims, but probably a majority of biologists since 1980 have gone along with the myth. The revisionists are misinformed (or misinforming).

It's in the best interests of the IDiots to promote the idea that all "Darwinists" believed in the "myth" of junk DNA and that it wasn't until the predictions of the IDiots were confirmed (not) that the biologists changed their minds.

The truth is somewhat different. Wells says, "Some people revise history by claiming that no mainstream biologists ever regarded non-protein-coding DNA as “junk.”" The truth is that the mainstream biologist community never, ever claimed that all non-coding DNA was junk. Most of them didn't even believe that a majority of our genome was junk.

The issue has come up many times over the past few years on blogs and newsgroups. The last time I took a poll was a few years ago and here are the results.


As you can see, there's a wide range of opinion among people who read Sandwalk. I think this is a pretty good reflection of the opinions of most biologists.

In responding to the question, Wells makes one serious error when he claims that biologists promoted junk DNA because it "provides evidence for Darwinian evolution." It does nothing of the sort. In fact, it goes against any prediction of Darwinian evolution by natural selection. The reason why the concept of (huge amounts of) junk DNA was resisted by so many biologists was because of this conflict.

Wells also says that junk DNA was promoted by some biologists because it "provides evidence ... against intelligent design." This is partly true, especially when the arguments center on conserved pseudogenes. That part of junk DNA (pseudogenes) is accepted by almost all biologists but it's only a tiny part of our genome. There is no evidence to suggest that pseudogenes are anything but junk and all the evidence indicates that we have thousands of them in our genome. (If they have a function then they aren't pseudogenes.)

Many mainstream biologists have supported the idea that a majority of our genome is junk. There's no denying that. I agree with them. None of them are changing their minds in spite of what Jonathan Wells is telling you. What Wells is doing is picking sides in a genuine scientific dispute. He could have done this 30 years ago and the result would have been the same. The genuine scientific controversy is not about to be resolved and there's no new evidence that seals the case one way or the other.

In my opinion, our genome is almost 90% junk DNA and that's the view that's going to win in the end.

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Nessa Carey and New Scientist don't understand the junk DNA debate

There's a new book on junk DNA due to be published at the end of March. It's called Junk DNA: A Journey through the Dark Matter of the Genome. The author is someone named Nessa Carey. Here's her bio ....

Nessa Carey has a virology PhD from the University of Edinburgh and is a former Senior Lecturer in Molecular Biology at Imperial College, London. She worked in the biotech and pharmaceutical industry for thirteen years and is now International Director for the UK's leading organisation for technology transfer professionals. She lives in Norfolk and is a Visiting Professor at Imperial College.

Pretty impressive.

Here's how she describes her view of the human genome.

Note to David Klinghoffer, When You find Yourself in a Hole, Stop Digging

Some of you might recall the recent Chromosome 2 kerfuffle. It started when Carl Zimmer asked David Klinghoffer a simple question. Zimmer asked him to describe the evidence to support his claim that the fusion site didn't look like it should if two primitive ape chromosomes had fused to produce human chromosome 2.

Rather than simply answer the question, the IDiots circled the wagons then went into attack mode. Eventually, after a lot of pressure, they got around to answering the question; apparently there is no evidence to support their claim [And Finally the Hounding Duck Can Rest].

Of course by then they were so deep in their hole that the sun don't shine.

Jonathan Wells Talks About Genetic Load

Most people don't understand the positive evidence for junk DNA—this includes most scientists. Paulmc tried to convince the readers on Uncommon Descent that they had been misinformed about junk DNA. The fact that our genome has huge amounts of junk DNA is not just an argument from ignorance—an argument that most IDiots are familiar with—because there are several good reasons for concluding that most DNA has to be junk.

Wells addressed those arguments in: Jonathan Wells on Darwinism, Science, and Junk DNA.

"Enlightened" scientist at the University of Colorado busts the myth that all non-coding DNA is junk!

We've known for 60 years that some non-coding DNA has a function but the latest generation of scientists thinks this was only discovered in their lifetime. Writer Kara Mason posts an article on the Department of Biomedical Informatics website at the University of Colorado.

Google's "Generative AI" lies about junk DNA

Every now and then I check Google to see if there's any news about junk DNA. I use "junk DNA" as my search query.

The first thing I see at the top of the results page is a summary of the topic created by Google's Generative AI, which it claims is experimental. The AI summary is different every time you start a new search but all of the responses are similar in that they criticize the idea of junk DNA. Here's an example from today,

The Encyclopedia of Evolutionary Biology revisits junk DNA

The Enclyopedia of Evolutionary Biology is a four volume set of articles by leading evolutionary biologists. An online version is available at ScienceDirect. Many universities will have free access.

I was interested in what they had to say about junk DNA and the evolution of large complex genomes. The only article that directly addressed the topic was "Noncoding DNA Evolution: Junk DNA Revisited" by Michael Z. Ludwig of the Department of Ecology and Evolution at the University of Chicago. Ludwig is a Research Associate (Assistant Professor) who works with Martin Kreitman on "Developmental regulation of gene expression and the genetic basis for evolution of regulatory DNA."

As you could guess from the title of the article, Michael Ludwig divides the genome into two fractions; protein-coding genes and noncoding DNA. The fact that organismal complexity doesn't correlate with the number of genes (protein-coding) is a problem that requires an explanation, according to Ludwig. He assumes that the term "junk DNA" was used in the past to account for our lack of knowledge about noncoding DNA.

Eukaryotic genomes mostly consist of DNA that is not translated into protein sequence. However, noncoding DNA (ncDNA) has been little studied relative to proteins. The lack of knowledge about its functional significance has led to hypotheses that much nongenic DNA is useless "junk" (Ohno, 1972) or that it exists only to replicate itself (Doolittle and Sapienza, 1980; Orgel and Crick, 1980).

Ludwig says that we now know some of the functions of non-coding DNA and one of them is regulation of gene expression.

These regulatory sequences are distributed among selfish transposons and middle or short repetitive DNAs. The genome is an extremely complex machine; functionally as well as structurally it is generally not possible to disentangle the regulatory function from the junk selfish activity. The idea of junk DNA needs to be revisited.

Of course we all know about regulatory sequences. We've known about this function of non-coding DNA for half a century. The question that interests us is not whether non-coding DNA has a function but whether a large proportion of noncoding DNA is junk.

Ludwig seems to be arguing that a significant fraction of the mammalian genome is devoted to regulation. He doesn't ever specify what this fraction is but apparently it's large enough to "revisit" junk DNA.

The biggest obstacle to his thesis is the fact that only 8% of the human genome is conserved (Rands et al., 2014). Ludwig says that 1% of the genome is coding DNA and 7% "has a functional regulatory gene expression role" according to the Rands et al. study. This is somewhat misleading since Rands et al. specifically mention that not all of this conserved DNA will be regulatory.

All of this is consistent with a definition of function specifying that it must be under negative selection (i.e. conserved). It leads to the conclusion that about 90% of the human genome is junk. That doesn't require a re-evaluation of junk.

In order to "revisit" junk DNA, the proponents of the "complex machine" view of evolution must come up with plausible reasons why lack of sequence conservation does not rule out function. Ludwig offers up the standard rationales ...

1. Some ultra-conserved sequences don't seem to have a function and this "shows that the extent of sequence conservation is not a good predictor of the functional importance of a sequence."
2. The amount of conserved sequence depends on the alignment and alignment is difficult.
3. About 40%-70% of the noncoding DNA in Drosophila melanogaster is under functional constraint within the species but not between D. melanogaster and D. simulans. Therefore, some large fraction of functional regulatory sequences might only be conserved in the human lineage and it won't show up in comparisons between species. (Does this explain onions?)

The idea here is that there is rapid turnover of functional DNA binding sites required for regulation but the overall fraction of DNA devoted to regulation remains large. This explains why there doesn't seem to be a correlation between the amount of conserved DNA and the amount that can possibly be devoted to regulating gene expression. The argument implies that much more than 7% of the genome is required for regulation. The amount has to be >50% or so in order to justify overthrowing the concept of junk DNA.

That's a ridiculous number, but so is 7%. Imagine that "only" 7% of the genome is functionally involved in regulating expression of the protein-coding genes. That's 224 million base pairs of DNA or approximately 10 thousand base pairs of cis-regulatory elements (CREs) for every protein-coding gene.

There is no evidence whatsoever that even this amount (7%) of DNA is required for regulation but Ludwig would like to think that the actual amount is much greater. The lack of conservation is dismissed by assuming rapid turnover while conserving function and/or stabilizing selection on polymorphic sequences.

The problem here is that Ludwig is constructing a just-so evolutionary story to explain something that doesn't require an explanation. If there's no evidence that a large fraction of the genome is required for regulation then there's no problem that needs explaining. Ludwig does not tell us why he believes that most of our genome is required for regulation. Maybe it's because of ENCODE?

Since this is published in the Encyclopedia of Evolutionary Biolgoy, I assume that this sort of evolutionary argument resonates with many evolutionary biologists. That's sad.

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Rands, C. M., Meader, S., Ponting, C. P., and Lunter, G. (2014) 8.2% of the Human Genome Is Constrained: Variation in Rates of Turnover across Functional Element Classes in the Human Lineage. PLoS Genetics, 10(7), e1004525. [doi: 10.1371/journal.pgen.1004525]

More Junk DNA Fallacies

 
BiOpinionated is a blog written by a molecular biologist named Nils Reinton. He tries to see every side of an argument but there are times when this attempt goes astray.

The "debate" over junk DNA is an example. Here's how Nils responed to claims by Ryan Gregory and me that most of our genome is junk [How to have your cake, eat it, and then complain].

First: State that most of our genome is junk.

Second: When more and more promoters, enhancers, repressors and other regulatory elements are discovered, claim that this of course was not included in the definition of “most of the genome”. The perfect excuse because it means you’ll never be wrong.

Last: Complain when the press does not understand that “most of our DNA” actually meant “much of our DNA , but with a lot of exceptions” and that science reporters don’t intuitively know which exceptions these are.

Post written using the zpen in dire agony over extremely poor science communication from the same persons who most eagerly criticize science communication from others.[see the original article for links - LAM]

Oh dear. There's so much wrong with the logic of this posting that I hardly know where to begin.

Nils is mostly upset about a recent posting on Genomicron: The Junk DNA myth strikes again (next up: media hype). This isn't very complicated so let me give you the short version.

Most of our genome is junk. That does not mean that all of our genome is junk and it certainly never meant (among intelligent scientists) that all of our non-coding DNA is junk. Here's a short list of non-coding DNA that is absolutely essential in our genome: all genes that produce functional RNAs instead of proteins; all regulatory sequences including enhancers; sequences that control splicing and other RNA processing events such as capping and polyadenylation; some 5′-leaders and 3′-tails of mRNA; chromatin domain markers (regulatory); scaffold attachment sites (SARs); some recombination hotspots; origins of replication; centromeres; telomeres.

Ryan was complaining about a paper that's about to be published in Molecular Biology and Evolution. The authors say this in their abstract.

Protein-coding sequences make up only about 1% of the mammalian genome. Much of the remaining 99% has been long assumed to be junk DNA, with little or no functional significance.

I agree with Ryan Gregory that this is extremely misleading. It implies that there are legitimate scientists who think that all non-coding DNA is junk. It would be far better to say something like this ...

Genes that encode proteins, and other genes, make up only a few percent of our genome. If you add in all of the other DNA sequences that are known to be essential you still can only account for no more than 5% of our genome. Most of the rest is thought to be junk DNA with no biological function. There are no respectable scientists who think that none of it will ever be shown to have a function but the general consensus among the defenders of junk DNA is that the vast majority of these DNA sequences, consisting mostly of defective transposons and pseudogenes, will turn out to have no function.

The authors of the paper go on to present evidence that about 5.4% of non-coding DNA has a function.

Big deal. That's not much more than what the textbooks have been saying for several decades.

Nils, there's an interesting debate going on about the amount of junk DNA in our genome. You're welcome to participate but please make sure you understand the issue and, please, don't spread false information. When we say that most of our genome is junk that does not mean that some of what we now consider to be junk DNA won't turn out to have a function. We're not that stupid—please don't imply that we are.

What we're saying is that the vast majority of DNA sequence in our genome is junk. I think the amount of junk is going to be >90%. That still leaves room for discovering a function for about twice as much DNA as we already know to be functional.

Get back to me when someone publishes solid evidence that more than 10% of our genome is essential.

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Subhash Lakhotia: The concept of 'junk DNA' becomes junk

Continuing my survey of recent papers on junk DNA, I stumbled upon a review by Subash Lakhotia that has recently been accepted in The Proceedings of the Indian National Science Academy (Lakhotia, 2018). It illustrates the extent of the publicity campaign mounted by ENCODE and opponents of junk DNA. In the title of this post, I paraphrased a sentence from the abstract that summarizes the point of the paper; namely, that the 'recent' discovery of noncoding RNAs refutes the concept of junk DNA.

Lakhotia claims to have written a review of the history of junk DNA but, in fact, his review perpetuates a false history. He repeats a version of history made popular by John Mattick. It goes like this. Old-fashioned scientists were seduced by Crick's central dogma into thinking that the only important part of the genome was the part encoding proteins. They ignored genes for noncoding RNAs because they didn't fit into their 'dogma.' They assumed that most of the noncoding part of the genome was junk. However, recent new discoveries of huge numbers of noncoding RNAs reveal that those scientists were very stupid. We now know that the genome is chock full of noncoding RNA genes and the concept of junk DNA has been refuted.

A Twofer

A few weeks ago David Klinghoffer criticized science bloggers for only going after "extremely marginal and daffy creationists." He challenged us to take on the "real scientists" like Jonathan M. [A Reason to Doubt the IDiots]

Today you're in for a treat, dear readers, 'cause I'm going to respond to a daffy creationist who happens to be Jonathan M. It's a twofer!

Required reading for the junk DNA debate

This is a list of scientific papers on junk DNA that you need to read (and understand) in order to participate in the junk DNA debate. It's not a comprehensive list because it's mostly papers that defend junk DNA and refute arguments for massive amounts of function. The only exception is the paper by Mattick and Dinger (2013).¹ It's the only anti-junk paper that attempts to deal with the main evidence for junk DNA. If you know of any other papers that make a good case against junk DNA then I'd be happy to include them in the list.

If you come across a publication that argues against junk DNA, then you should immediately check the reference list. If you do not see some of these references in the list, then don't bother reading the paper because you know the author is not knowledgeable about the subject.

Brenner, S. (1998) Refuge of spandrels. Current Biology, 8:R669-R669. [PDF]

Brunet, T.D., and Doolittle, W.F. (2014) Getting “function” right. Proceedings of the National Academy of Sciences, 111:E3365-E3365. [doi: 10.1073/pnas.1409762111]

Casane, D., Fumey, J., et Laurenti, P. (2015) L’apophénie d’ENCODE ou Pangloss examine le génome humain. Med. Sci. (Paris) 31: 680-686. [doi: 10.1051/medsci/20153106023] [The apophenia of ENCODE or Pangloss looks at the human genome]

Cavalier-Smith, T. (1978) Nuclear volume control by nucleoskeletal DNA, selection for cell volume and cell growth rate, and the solution of the DNA C-value paradox. Journal of Cell Science, 34(1), 247-278. [doi: PDF]

Doolittle, W.F. (2013) Is junk DNA bunk? A critique of ENCODE. Proc. Natl. Acad. Sci. (USA) published online March 11, 2013. [PubMed] [doi: 10.1073/pnas.1221376110]

Doolittle, W.F., Brunet, T.D., Linquist, S., and Gregory, T.R. (2014) Distinguishing between “function” and “effect” in genome biology. Genome biology and evolution 6, 1234-1237. [doi: 10.1093/gbe/evu098]

Doolittle, W.F., and Brunet, T.D. (2017) On causal roles and selected effects: our genome is mostly junk. BMC biology, 15:116. [doi: 10.1186/s12915-017-0460-9]

Eddy, S.R. (2012) The C-value paradox, junk DNA and ENCODE. Current Biology, 22:R898. [doi: 10.1016/j.cub.2012.10.002]

Eddy, S.R. (2013) The ENCODE project: missteps overshadowing a success. Current Biology, 23:R259-R261. [10.1016/j.cub.2013.03.023]

Graur, D. (2017) Rubbish DNA: The functionless fraction of the human genome Evolution of the Human Genome I (pp. 19-60): Springer. [doi: 10.1007/978-4-431-56603-8_2 (book)] [PDF]

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1. The paper by Kellis et al. (2014) is ambiguous. It's clear that most of the ENCODE authors are still opposed to junk DNA even though the paper is mostly a retraction of their original claim that 80% of the genome is functional.

Selfish genes and transposons

Back in 1980, the idea that large fractions of animal and plant genomes could be junk was quite controversial. Although the idea was consistent with the latest developments in population genetics, most scientists were unaware of these developments. They were looking for adaptive ways of explaining all the excess DNA in these genomes.

Some scientists were experts in modern evolutionary theory but still wanted to explain "junk DNA." Doolittle & Sapienza, and Orgel & Crick, published back-to-back papers in the April 17, 1980 issue of Nature. They explained junk DNA by claiming that most of it was due to the presence of "selfish" transposons that were being selected and preserved because they benefited their own replication and transmission to future generations. They have no effect on the fitness of the organism they inhabit. This is natural selection at a different level.

This prompted some responses in later editions of the journal and then responses to the responses.

Here's the complete series ...