How to Make a Scientific Argument

The debate over the amount of junk in our genome is a genuine scientific debate. There are legitimate scientific points of view on both sides although the weight of evidence and logic is tilting heavily in favor of junk DNA. It looks more and more like most (~90%) of our genome is junk.

The problem with the debate is that the scientific literature is full of papers attacking junk DNA while there are very few papers promoting it. This is partly because there haven't been any new discoveries in favor of junk DNA. On the other hand, there have been quite a few discoveries showing that some small part of the genome that was thought to be junk might have a function. Even though these discoveries make an insignificant contribution to the big picture, they are often blown up out of all proportion and promoted as an end to junk DNA.

A recent paper in PLoS Genetics illustrates the problem.

The ENCODE Data Dump and the Responsibility of Science Journalists

ENCODE (ENcyclopedia Of DNA Elements) is a massive consortium of scientists dedicated to finding out what's in the human genome.

They published the results of a pilot study back in July 2007 (ENCODE, 2007) in which they analyzed a specific 1% of the human genome. That result suggested that much of our genome is transcribed at some time or another or in some cell type (pervasive transcription). The consortium also showed that the genome was littered with DNA binding sites that were frequently occupied by DNA binding proteins.

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Genomes & Junk DNAAll of this suggested strongly that most of our genome has a function. However, in the actual paper the group was careful not to draw any firm conclusions.

... we also uncovered some surprises that challenge the current dogma on biological mechanisms. The generation of numerous intercalated transcripts spanning the majority of the genome has been repeatedly suggested, but this phenomenon has been met with mixed opinions about the biological importance of these transcripts. Our analyses of numerous orthogonal data sets firmly establish the presence of these transcripts, and thus the simple view of the genome as having a defined set of isolated loci transcribed independently does not seem to be accurate. Perhaps the genome encodes a network of transcripts, many of which are linked to protein-coding transcripts and to the majority of which we cannot (yet) assign a biological role. Our perspective of transcription and genes may have to evolve and also poses some interesting mechanistic questions. For example, how are splicing signals coordinated and used when there are so many overlapping primary transcripts? Similarly, to what extent does this reflect neutral turnover of reproducible transcripts with no biological role?

This didn't stop the hype. The results were widely interpreted as proof that most of our genome has a function and the result featured prominently in the creationist literature.

Junk DNA and the Scientific Literature

 
A discussion about junk DNA has broken out in the comments to Monday's Molecule #128: Winners.

Charlie Wagner, an old talk.origins fan, wonders why junk DNA advocates are still around given that there have been several recent papers questioning the idea that most of our genome is junk.

Charlie asks ...

So why are Larry and many others still clinging to the myth of "junk DNA"? Do they not read the literature?

Of course we read the literature, Charlie, but unlike you we read all of the literature. You can't just pick out the papers that support your position and assume that the question has been settled.

The skill in reading the scientific literature is to put things into perspective and maintain a certain degree of skepticism. It's just not true that everything published in scientific journals is correct. An important part of science is challenging the consensus and many scientists try to make their reputation by coming up with interpretations that break new ground. The success of science depends on the few that are correct but let's not forget that most of them turn out to be wrong.

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Genomes & Junk DNA
The trick is to recognize the new ideas that may be on to something and ignore those that aren't. This isn't easy but experienced scientists have a pretty good track record. Inexperienced scientists may not be able to distinguish between legitimate challenges to dogma and ones that are frivolous. The problem is even more severe for non-scientists and journalists. They are much more likely to be sucked in by the claims in the latest paper—especially if it's published in a high profile journal.

Lots of scientists don't like the idea of junk DNA because it doesn't fit into their view of how evolution works. They gleefully announce the demise of junk DNA whenever another little bit of noncoding DNA is discovered to have a function. They also attach undue significance to recent studies showing that a large part of mammalian genomes are transcribed at one time or another in spite of the fact that this phenomenon has been known for decades and is perfectly consistent with what we know about spurious transcription.

I've addressed many of the specific papers in previous postings. You can review my previous postings by clicking on the Theme Box URL. The bottom line is "don't trust everything you read in the recent scientific literature."

Another good rule of thumb is never trust any paper that doesn't give you a fair and accurate summary of the "dogma" they are opposing. When you challenge the concept of junk DNA, for example, it's not good enough to just present a piece of new evidence that may not fit the current "dogma." You also have to deal with all the evidence that was used to create the consensus view in the first place and show how it can be better explained by your new model. A good place to start is The Onion Test.

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The figure is from Mattick (2007), an excellent example of what I'm talking about. This is a paper attacking the current consensus on junk DNA but in doing so it uses a figure that reveals an astonishing lack of understanding of genomes. This makes everything else in paper suspect. The figure was chosen by Ryan Gregory to be the classic example of a Dog's Ass Plot.

Mattick, J.S. (2004) The hidden genetic program of complex organisms. Sci Am. 291:60-67.

Revisiting the genetic load argument with Dan Graur

The genetic load argument is one of the oldest arguments for junk DNA and it's one of the most powerful arguments that most of our genome must be junk. The concept dates back to J.B.S. Haldane in the late 1930s but the modern argument traditionally begins with Hermann Muller's classic paper from 1950. It has been extended and refined by him and many others since then (Muller, 1950; Muller, 1966).

Does Excess Genomic DNA Protect Against Mutation?

Many eukaryotic genomes have a large amount of "excess" DNA that doesn't have any of the functions we normally assign to DNA (protein-coding, regulatory, origins of replication, centromeres, RNA genes etc.). Many of us think this is junk DNA. It has no function and could easily be dispensed with.

One of the adaptive explanations for this excess DNA is that it protects the functional DNA from mutations. Ryan Gregory thinks this is a serious scientific hypothesis even though he's skeptical. He has a wonderful post that reviews the history of the idea and how the hypothesis should be tested [Does junk DNA protect against mutation?].

The bottom line is that this hypothesis is not taken very seriously by the scientific community for some very good reasons.

First, most spontaneous mutations in the germ line seem to be due to errors in DNA replication. The overall rate of evolutionary change is consistent with the mutation rate of DNA replication + repair, suggesting that it is the dominant form of mutation. This mutation rate is based on the number of nucleotides replicated. What this means is that the rate of mutation in functional DNA is independent of how much other DNA is being replicated. Excess DNA offers no protection from the spontaneous error rate of DNA replication.

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However, the protection hypothesis may be applicable to other kinds of mutation such as those caused by chemicals or ionizing radiation. In multicellular organisms such as animals, fungi, and plants, this possible protection may prolong the lifetime of somatic cells or prevent them from becoming deregulated (e.g., cancer).

The idea is that excess DNA may shield the functional DNA from the effects of these mutagens but this would only work if the excess DNA was specifically organized so that it surrounded the functional DNA and provided physical shielding. There's no evidence that this is the case and, furthermore, it doesn't make much sense. The functional DNA in a nucleus is already shielded by lots of proteins, lipids and membranes so it's unlikely that a bit more DNA is going to make a difference.

Not only that, but some kinds of DNA damage caused by these mutagens will cause strand breakage. What does that mean? It means that the larger the genome the greater the chance that damage will occur. In other words, excess DNA leads to greater rates of mutation, not lower rates of mutation, for those types of mutagens. Ryan Gregory shows results from several studies during the 1970s that establish that fact.

I sympathize with Ryan's call for experimental support of the hypothesis but I'd also like to point out that not only does it not have direct evidence to back it up but it's not even theoretically feasible. It's just a bad hypothesis based largely on a misunderstanding of mutations and how they arise.

Also, the protection hypothesis doesn't pass The Onion Test which is one of the first requirements for an adaptive explanation of junk DNA.

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Stephen Jay Gould and Sydney Brenner Agree on Junk DNA

It's no secret that I'm a big fan of Stephen Jay Gould. I'm also a big fan of Sydney Brenner. Here's Gould writing in The Structure of Evolutionary Theory (pages 1269-1270). This is long and complicated but if you want to understand junk DNA and why it conflicts with Darwinism, then you've got to make the effort. I especially like the idea that Gould understands the difference between junk DNA, which can't be explained by any adaptive mechanism, and "selfish DNA," which isn't junk and has a Darwinian explanation. Many people don't get this.

Gould and Brenner are talking about repetitive DNA. This includes highly repetitive sequences of simple repeats and moderately repetitive sequences that include the transposons.

Junk & Jonathan: Part 7—Chapter 4

This is part 7 of my review of The Myth of Junk DNA. For a list of other postings on this topic see the link to Genomes & Junk DNA in the "theme box" below or in the sidebar under "Themes."

The title of Chapter 4 is Introns and the Splicing Code. It opens with a brief description of eukaryotic genes and alternative splicing. Here's a better description of splicing for those who want a quick refresher: RNA Splicing: Introns and Exons. Alternative splicing is when a transcript can be spliced in at least two different ways to produce 2 distinct mRNAs. Each of them will make a different, but related, protein. The process has been known for thirty years and the mechanism is well-understood. It's described very well in a Wikipedia article: Alternative Splicing.

Here's some important background information from Junk in Your Genome: Protein-Encoding Genes.

The minimum size of a eukaryotic intron is less than 50 bp. For a typical mammalian intron, the essential sequences in the introns are: the 5′ splice site (~10 bp); the 3′ splice site (~30 bp): the branch site (~10 bp); and enough additional RNA to form a loop (~30 bp). This gives a total of 80 bp of essential sequence per intron or 20,500 × 7.2 × 80 = 11.8 Mb. Thus, 0.37% of the genome is essential because it contains sequences for processing RNA.

In other words, assuming that introns aren't all junk we can estimate how much of the intron sequence is essential for it's function by taking into account the known regulatory sequences and the amount needed to form a loop.

The rest of an intron sequence may be junk. If it is, then we would expect to see two things.

• Considerable variation is intron size from species to species.
• Frequent examples of transposons, endogenous retroviruses, and even other genes inserting into introns.

This is exactly what we see [Junk in Your Genome: Intron Size and Distribution]. There's no indication that intron sequences are conserved or essential.

Jonathan Wells explains that alternative splicing is important in some genes. He is correct. He then explains that there are sequences in introns that regulate alternative splicing. He's correct about that as well. We've been writing this up in the textbooks and teaching it in introductory biochemistry courses since early in the 1980s. The classic example is the determination of sex in Drosophila—it's largely controlled by alternative splicing and we know a great deal about which proteins bind to which sequences in the introns to promote or repress a given splice site [Sex in the fruit fly Drosophila melanogaster].

Nothing new here. We know about binding sites and we know that most of them are 10 bp or less. Their presence makes no significant difference in our calculations of junk DNA. I get the distinct impression that Wells and the other IDiots don't really understand splicing and alternative splicing.

Here's a series of blog posts I did last year when Richard Sternberg tried to pretend that he knew something about molecular biology and alternative splicing. Later on, Jonathan Wells weighs in to try and help his friend but ends up showing that he too, is in way over his head.

Creationists, Introns, and Fairly Tales

IDiots Do Arithmetic a Second Time - Same Result

Jonathan Wells Weighs in on Alternative Splicing

Having "proven" that something like 0.03% of our genome may not be junk, Wells then goes on to describe other sequences that are found in introns. Some of these are regulatory sequences or enhancers. These aren't common, but they do exist. They're usually located in the 5′ intron and they are often associated with alternative transcription start sites. The total amount of non-junk DNA due to regulatory sequences has already been taken into account in my calculations (Junk in Your Genome: Protein-Encoding Genes) and it doesn't matter whether these regulatory sequences are intergenic or included within an intron.

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Genomes
& Junk DNAWells also notes that many genes for small RNAs are located within introns. These include some of the genes for the splicing machinery, tRNA genes, snoRNA genes etc. He doesn't mention that introns are also loaded with Alu sequences and other transposable elements (mostly defective). The presence of the these insertions show us that cells don't discriminate between intron sequences that make up 25% of the genome and the remaining 65% that's mostly junk. They are all targets for inserting small genes and transposons. No surprises here.

Finally, on the last page of Chapter 4, Wells devotes two paragraphs to a genuine scientific argument. The idea is that long introns might be necessary to delay transcription. This idea has been around for a long time. It was originally proposed over 25 years ago as an explanation for the long introns found in Drosophila HOX genes, especially Ubx.

If a gene has several long introns it can stretch out over 100 kb (100,000 bp). The typical RNA polymerase II elongation complex transcribes at a rate of 50 bp per second so it will take more than 30 minutes to transcribe these long genes. The idea is that the presence of long introns delays appearance of the regulatory proteins during development. This seems unlikely because there are many other, more efficient, ways of regulating gene expression. As a matter of fact, the argument can be easily turned upside down.

Genes that need to be transcribed quickly have very short introns or none at all. The heat shock inducible genes, for example, don't even have introns. These genes need to be expressed rapidly when a cell encounters stressful conditions. Their non-inducible homologues all have respectable introns so it looks like there has been selection for losing introns in these genes.

Similarly, there are often testes specific genes than lack introns. The supposition is that these variant family members have lost introns so they can be quickly transcribed during spermatogenesis. The globin genes have relatively small introns and they are also expressed at a high rate in erythroblasts.

Genes that are infrequently transcribed tend to accumulate large introns. This includes most developmentally regulated transcription factors that only need to produce a small number of proteins at a specific time in the life of the organism. These observations are consistent with the idea that excess junk in intron sequences is removed when necessary. It's actually evidence that those sequences are junk.

So far we covered the evidence of probable function in Chapter 3 and seen that Wells does not critically examine the data on pervasive transcription but simply assumes it is correct. He then makes the unsubstantiated claim that evidence of transcription is evidence of function. He's wrong about the claim that most of our genome is transcirbed and he's wrong to assume that all transcripts are functional. Nothing in that chapter supported his claim that junk DNA is a myth.

In this chapter we see the first evidence for specific functions of noncoding DNA. The presence of regulatory sequences in introns has been well known for decades and it has no impact on the estimates of junk DNA. The idea that big introns might be adaptive regardless of sequence is possible but not reasonable. In fact, the evidence suggests strongly that big introns full of junk DNA can be detrimental in some cases. Nothing in Chapter 4 provides convincing evidence that junk DNA is a myth.

What about pseudogenes? Are they a myth? That's covered in Chapter 5.

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A note about references
The IDiots are promoting this book by bragging about multiple references that challenge the concept of junk DNA [Jonathan Wells offers over 600 references to recent peer-reviewed literature]. Chapters 1 and 2 were introductions to the problem. They had a total of 51 references. Chapter 3 had 62 references but, as we have seen, they don't add up to a convincing case. There were plenty of references that should have been included if a scientific case was going to be made. Chapter 4 has 63 references but only three of them address a substantive argument against junk DNA in introns. All three make the same point; namely that long introns delay transcription.

That's a total of 176 references so far with nothing much to show for them. There are 432 references in the rest of the book. There are 26 references to known IDiots including 8 references to the work of Jonathan Wells.

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Birds of a feather: epigenetics and opposition to junk DNA

There's an old saying that birds of a feather flock together. It means that people with the same interests tend to associate with each other. It's extended meaning refers to the fact that people who believe in one thing (X) tend to also believe in another (Y). It usually means that X and Y are both questionable beliefs and it's not clear why they should be associated.

I've noticed an association between those who promote epigenetics far beyond it's reasonable limits and those who reject junk DNA in favor of a genome that's mostly functional. There's no obvious reason why these two beliefs should be associated with each other but they are. I assume it's related to the idea that both beliefs are presumed to be radical departures from the standard dogma so they reinforce the idea that the author is a revolutionary.

Or maybe it's just that sloppy thinking in one field means that sloppy thinking is the common thread.

Here's an example from Chapter 4 of a 2023 edition of the Handbook of Epigenetics (Third Edition).

The central dogma of life had clearly established the importance of the RNA molecule in the flow of genetic information. The understanding of transcription and translation processes further elucidated three distinct classes of RNA: mRNA, tRNA and rRNA. mRNA carries the information from DNA and gets translated to structural or functional proteins; hence, they are referred to as the coding RNA (RNA which codes for proteins). tRNA and rRNA help in the process of translation among other functions. A major part of the DNA, however, does not code for proteins and was previously referred to as junk DNA. The scientists started realizing the role of the junk DNA in the late 1990s and the ENCODE project, initiated in 2003, proved the significance of junk DNA beyond any doubt. Many RNA types are now known to be transcribed from DNA in the same way as mRNA, but unlike mRNA they do not get translated into any protein; hence, they are collectively referred to as noncoding RNA (ncRNA). The studies have revealed that up to 90% of the eukaryotic genome is transcribed but only 1%–2% of these transcripts code for proteins, the rest all are ncRNAs. The ncRNAs less than 200 nucleotides are called small noncoding RNAs and greater than 200 nucleotides are called long noncoding RNAs (lncRNAs).

In case you haven't been following my blog posts for the past 17 years, allow me to briefly summarize the flaws in that paragraph.

• The central dogma has nothing to do with whether most of our genome is junk
• There was never, ever, a time when knowledgeable scientists defended the idea that all noncoding DNA is junk
• ENCODE did not "prove the significance of junk DNA beyond any doubt"
• Not all transcripts are functional; most of them are junk RNA transcribed from junk DNA

So, I ask the same question that I've been asking for decades. How does this stuff get published?

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The Function Wars Part VI: The problem with selected effect function

The term "Function Wars" refers to the debate over the meaning of 'function,' especially in the context of junk DNA.¹ That debate intensified in 2012 after the ENCODE publicity campaign that tried to redefine function to mean anything they want as long as it refutes junk DNA. This is the sixth in a series of posts exploring the debate and why it's important, or not. Links to the other five posts can be found at the bottom or this post.

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.
Stephen Jay Gould (1982)Much of the discussion seems like quibbling over semantics but I'm reminded of a similar debate over the mode of evolution: is it gradual or punctuated? As Gould pointed out in 1982, there's a serious issue underlying the debate—an issue that shouldn't get lost in bickering over the meaning of 'gradualistic.' The same warning applies here. It's important to determine how much of the human genome is junk and that requires an understanding of what we mean by junk DNA. However, it's easy to get distracted by focusing on the exact meaning of the word 'function' instead of looking at the big picture.

Jonathan M Flunks the Onion Test, Again

 

A few weeks ago I explained why Jonathan M is an IDiot [A Twofer]. The topic was junk DNA. Jonathan M had posted an article on Uncommon Descent where he claimed that The Onion Test is an argument in favor of junk DNA [Thoughts on the “C-Value Enigma”, the “Onion Test” and “Junk DNA”].

I explained, as politely as I could (not), that the onion test was not an argument in support of junk DNA. It's a "test" for those who think they can explain the presence of large amounts of supposedly functional DNA that looks a lot like junk. The "test" is to apply your reasoning to the genomes of various onion species to see if it makes sense.

Do you think that the excess DNA protects against mutations? Then why do some onions need a lot more protection than humans?

Do you think that the extra DNA can be explained by alternative splicing? Why do some onion species need more alternative splicing than others?

Do you think that most of the extra DNA is required for regulating gene expression? Then why do onions need more sophisticated regulation than humans?

This ain't rocket science. The description of the Onion Test is pretty easy to understand—unless, of course, you are an IDiot.

Jonathan M has taken another shot at attacking the Onion Test. This time his article appears on the official blog of The Discovery Institure: Why the "Onion Test" Fails as an Argument for "Junk DNA". The title sort of gives it away, doesn't it? We're still dealing with an IDiot.

Briefly stated, the often cited "onion test" observes that onion cells have many times more DNA than human cells do. And since the onion is considered to be relatively simple as compared to us, this discrepancy -- it is argued -- can only be accounted for if the preponderance of its DNA is, in fact, junk or non-functional. Let's see whether the concept really holds any water.

Let's go over this one more time. The Onion Test is a "test." (Look up the word "test" in the dictionary.) It's designed as a thought experiment to test a hypothesis about the possible function of large amounts of noncoding DNA. If you think you have an explanation for why most of the human genome has a function then you should explain how that accounts for the genomes of onions. Ryan Gregory knew that most so-called explanations look very silly when you try using them to account for genome size in onion species.

The Onion Test is not an argument in favor of junk DNA. It's a reality check on speculations about function.

Jonathan M still doesn't get it.

Are we surprised?

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Jonathan Wells Talks About Sequence Conservation

Paul McBride (paulmc) tried to convince the readers on Uncommon Descent that there was evidence for junk DNA. One of the lines of evidence has to do with sequence conservation. If most of the genome sequences are not conserved between species this strongly suggests that they have no function, although it doesn't rule out a function that is independent of sequence.

Wells addresses this argument in: Jonathan Wells on Darwinism, Science, and Junk DNA. Before analyzing his response, it's worth reviewing what he wrote in The Myth of Junk DNA.

In chapter 5, Wells talks about sequence conservation as evidence of function—specifically the fact that the sequences of some potential pseudogenes are more conserved that would be expected if they were really pseudogenes [Junk & Jonathan: Part 8—Chapter 5]. That's an important argument and, if true, it would point to a function. The irony is that Wells doesn't believe in common descent so, from his perspective, these are not conserved sequences due to negative natural selection. Nevertheless, he is happy to use evolutionary arguments whenever it suits him.

Five questions for Intelligent Design Creationists

A few Intelligent Design Creationists are beginning to learn about evolution. A few days ago, I speculated about what would happen if they really did start to understand modern evolutionary theory and the massive amount of data that supports the basic facts of evolution [What would happen if Intelligent Design Creationists understood evolution?].

Vincent Torley has responded. He illustrates the problems they will face and reveals some of the rationalizations that they might use to avoid the most severe symptoms of cognitive dissonance [see Professor Larry Moran poses five questions for the ID movement].

Let's take a look at what has to say. Remember that Vincent Torley doesn't speak for all Intelligent Design Creationists but he does have posting privileges on Uncommon Descent and he is frequently praised by some of the ID leaders who post there. I think we can assume that his views are typical.

Here's his response to each of the five questions.

Advice from Jonathan Wells on Junk DNA

 

Copied from Uncommon Descent (Denyse O'Leary): What advice, on junk DNA, would Jonathan Wells give Francis Collins or Richard Dawkins?.

From the Salvo Magazine interview with Jonathan Wells, by Casey Luskin. Wells is the author of The Myth of Junk DNA:

If you could have lunch with Francis Collins and Richard Dawkins, what would you say to them about their use of the “junk DNA” argument? [that there is no design in life]

Actually, Collins no longer relies on “junk DNA.” In 2007 he announced in an interview for Wired magazine that he had “stopped using the term.” In 2010 he wrote that “discoveries of the past decade, little known to most of the public, have completely overturned much of what used to be taught in high school biology. If you thought the DNA molecule comprised thousands of genes but far more ‘junk DNA,’ think again” (The Language of Life, pp. 5–6). Unfortunately, his followers at the BioLogos Institute (which he founded) seem to be unaware of this, because they continue to promote the myth that most of our DNA is junk. I would encourage Collins to set them right.

UD News does not think Collins would succeed. They are not Collins’s followers, they are Darwin’s men. They do not seek more knowledge than Darwin had. They seek to make what he knew part of the bedrock of Christianity.

Unlike Collins, Dawkins seems utterly oblivious to recent developments in genomics. I would encourage him to read some of the scientific literature.

Why? Dawkins can command international attention for not keeping up to date – because millions of tax burdens feel he speaks for them – and they don’t need to keep up to date either. Their champions are fronts for the dead orthodoxies that keep them in place.

Dear Jonathan Wells and Denyse O'Leary,

I have read The Myth of Junk DNA and I have read the scientific literature. What advice would you give me?

Why don't you respond to my review of The Myth of Junk DNA? What are you afraid of?

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Kat Arney interviews me on her podcast

I had a long chat with Kat Arney a few weeks ago and she has now taken the best parts of that conversation and put them in her latest Genetics Society podcast: Genes, junk and the 'dark genome'. My comments are in the last twelve minutes. At the end, Kat asks me "Is there like one thing you would really want a student or researcher, working in genetics today to really understand about the human genome?"

Kat was kind enough to write a blurb for my book last year where she said,

What's in Your Genome? is a thought-provoking and pugnatious book that will make you wonder afresh at the molecular intracies of life. When it comes to our genomes, we humans are nothing special—Moran makes a convincing argument that the vast majority of our sloppy human genome is not mysterious genetic treasures but boring junk.

In this podscast, she combines my thoughts on the human genome with those of two people who don't agee with the idea that the human genome is full of junk. Here's a brief summary of their positions.

Naomi Allen is Chief Scientist at UK Biobank, a consortium that's sequencing the genomes of UK citizens. So far, they've published data on 500,000 genome sequences. I wrote about one of their more significant findings last year (August, 2022) where they reported on the fraction of the human genome that was under purifying selection. This is an excellent proxy for functional DNA and the results are in line with (my) expectations: less that 10% of the genome is conserved and most of it is in the non-coding fraction [Identifying functional DNA (and junk) by purifying selection.

It's too bad that Kat's interview with Naomi Allen doesn't mention that important result, especially since the podcast is about junk DNA. Here's how Naomi Allen begins her part of the interview.

Whole genome sequencing enables researchers to look at all of the genetic variation across the entire genome. So not just in the 2% of the genome that encodes for proteins, but all of the genetic variation, much of which was previously considered "junk DNA" precisely because we didn't know what it did.

This is disappointing for two important reasons. First, surely in 2023 we've gone beyond the tired myth that all of the information in the human genome was concentrated in coding DNA? Second, no knowledgeable scientist ever said that all non-coding DNA was junk DNA and the idea of junk DNA was not based on ignorance so surely it's time to stop repeating that myth as well.

The rest of that interview focuses on how mapping genetic variation could contribute to our understanding of health and disease. I would have loved to ask how Biobanks proposes to do this if most of the variation is in junk DNA and also ask whether mutations in junk DNA can contribute to genetic disease. (They can.)

Danuta Jeziorska is the CEO of Nucleome Therapeutics, a company that's described as "spun out of Oxford University with a new set of technologies for exploring the dark genome." Kat asks her about the dark genome and here's her response.

So if you think about it, we have 22,000 genes in our genome, and we can compare that to having 22,000 ingredients in the fridge. We use the same set of ingredients to create different meals, just like how we have the same DNA within each cell, but then we have hundreds of different cell types. So this dark genome determines the combination of ingredients of the genes that you take and at which level you use them, to produce the different cell types that build our body. And you can just imagine that if you make a mistake in that - so let's say that you add the wrong ingredients in the wrong meal, you can mess up the meal. And in this same way you can mess up the cell type. So if you, for example, if you don't produce enough of haemoglobin to transport oxygen around the body, you will end up with a genetic form of anaemia or if you turn on a gene that's not supposed to be turned on, like an oncogene, you may end up having cancer.

So the dark genome is now very well understood as the mechanism that is causing diseases.

This is a slightly different definition of the dark genome than those I discussed in a recent post [What is the "dark matter of the genome"?]. In that post I suggested that most scientists were referring to all of the functions in non-coding DNA but Danuta Jeziorska seems to be restricting her use of "dark genome" to just regulatory sequences. In the rest of the interview she goes on to describe various types of regulatory sequences, with an emphasis on 3D structure, and to explain that many common genetic diseases are caused by mutations in regulatory sequences. Her company is using machine learning to find the functional elements in the dark genome and which variants are associated with disease. They are also investing in drug discovery.

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Discussing Junk DNA with an Adaptationist, Again

Nils Reinton is a molecular biologist working in the field of medical diagnostics and he has been challenging the concept of junk DNA in the comment section of a recent posting. The title of that posting, Everything Is There for a Reason?, was direct response to an earlier posting from Nils where he claimed that we shouldn't label DNA as "junk" because it's a science stopper.

During the discussion in the comment to my posting, I challenged Nils to answer a number of questions. He has responded on his blog SciPhu with Hey junk people, I accept your challenge (part I). I resonded to his answers in Discussing Junk DNA with an Adaptationist.

Now Nils has weighed in with Hey junk people, I accept your challenge (part II).

Q: Why is the Fugu genome so much smaller than that of other fish?

and

Q: When two similar species differ in genome size by a factor of two—probably due to an ancient polyploidization—is the majority of DNA in both species functional?

A: His argument is that since the genome size differs between species, much of it must be junk. But, you could easily use the same argument towards a function, by saying that the difference in genome size is a defining (functional) difference between species. We just do not know do we ! And, why does the difference in size not give you reason to speculate on function at least in parts of these regions ? Others have however, speculated far better than me on this topic, and a thorough introduction to such research can be found at junkdna.com and following this link to “The Principle of Recursive Genome Function“.

No, my argument was not that the extra DNA has to be junk just because there are two similar species that differ in the sizes of their genomes.

The question was directed at adaptationists who postulate a function for everything. I wanted to know the adaptationist explanation for those observations. What is it? Following a polyploidization is it possible that most of the DNA in the larger genome becomes non-junk right away?

Incidentally, by linking to the HoloGenomics website (junk.dna), Nils does not enhance his credibility.

Q: In the human lineage there are over one million Alu sequences. They all look like degenerate versions of 7SL RNA. Are all of these sequences functional? If so, what function could they be doing? And why do the human Alus look so different from the mouse ones?

A: I am not saying all Alu-elements are functional. On the “what is junk” scale, one extreme is that everything that hasn’t been ascribed a function is junk (Larry Moran’s position !?) and on the other end is “nothing is junk”. My position is somewhere in the middle: Some of the DNA in our genome is possibly junk. A number of individual Alu-elements will undoubtedly end up in the “junk”-category when more is known about our genome. That said, it has been shown that Alu-elements can constitute (parts of) regulatory and functional elements. It’s rather hard to tell which ones are functional by just looking at them. I therefore refuse to call them “junk” by default, - I strongly feel that the “junk”-label is a dismissal of any possible function(s) and should be used with caution if at all, - even for Alu-elements.

My position is that a huge amount of the DNA in our genomes is junk. That position is based on many different lines of evidence as well as on rational extrapolation from what we know and don't know about molecular biology and evolution.

Nobody is arguing that every single Alu element is junk. That would be stupid because we know for a fact that some of them have secondarily acquired a function. The point is whether most of this repetitive sequence can be reasonably assumed to be functional, and if so, what kind of function does the adaptationist imagine for most of these sequences?

In the absence of any reasonable functional explanation, and in the face of evidence that most Alu elements are degenerate retrotransposons, it is reasonable to adopt the working hypothesis that they are junk. That's not a science stopper. It's just common sense.

Q: Most intron sequences do not seem to have a function. Why does the size of introns in the same gene vary so much in related species and why isn’t the sequence conserved in most cases?

A: This argument is similar to the genome size argument above, and the answers for bullet 5 and 6 are equally valid here. Thus, there may be many reasons for a variation in intron size and this variation is not a very good argument to support the “junk” hypothesis. Also, the intron can contain regulatory elements and the c-gamma example above goes to show that introns can even contain functional (as in transcribed) genetic elements.

The fact that we have a few examples of functional intron sequences is no reason to assume that most of them are functional in the face of abundant evidence that they are not. That's a position that only a confirmed adaptationist would take.

This is a case where the exceptions tend to prove the rule not that the exceptions make a new rule.

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Two Heidelberg graduate students reject junk DNA

Science in School is a magazine for European science teachers. Two graduate students¹ have just published an article in the November issue: Not junk after all: the importance of non-coding RNAs.

Note: The article has been edited to remove some of the references to junk DNA and the editor has added the following disclaimer to the end of the article: Editor’s note: Some parts of the introduction and conclusion were rephrased to avoid any misunderstanding concerning the nature of ‘junk DNA’, which is not the focus of this article. Here's a link to the revised article: Not junk after all: the importance of non-coding RNAs. More changes are expected.

Not junk after all: the importance of non-coding RNAs

Originally assumed to be useless ‘junk DNA’, sections of the genome that don’t encode proteins have been revealed as a source of many important non-coding RNA structures.

The central dogma of molecular biology is that DNA is used as a template to create messenger RNA (mRNA), which in turn is translated into proteins that build the tissues in our bodies and carry out the main functions of our cells and organs. In other words, DNA → mRNA → proteins. Interestingly, though, only 2% of the DNA in our whole genome codes for proteins! So, what does the other 98% of the human genome do? In the mid-1900s, it was widely believed that a great part of our genome was useless, repetitive ‘junk DNA’. However, this belief goes against the evolution theory, which suggests that useless sequences would be eliminated from the genome since their maintenance requires energy. In the late 20th century and the early 21st century, this junk DNA has been shown to not only contain important regulatory elements for transcription, but also sequences that encode various non-coding RNAs that have functions in many cellular mechanisms.

I just finshed a podcast interview with Kat Arney and one of the questions she asked was what is the most important thing I'd like scientists to know about this topic. I picked evolution—I'd like modern researchers to understand that there's more to evolution than natural selection. You can see the problem in this example where two students who are working toward a Ph.D. at a top lab in Europe think that junk DNA "goes against the evolution theory."

That's sad. It's also sad that these two students think that 98% of our genome might be devoted to regulation and non-coding genes.

We need to focus on educating the next generation of scientists and that starts with educating science teachers. This is not the way to do it.

Here's the contact information for Science in School. I've written the editor at editor@scienceinschool.org. Please send a message if you are as concerned about the spread of scientific misinformation as I am.

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Zuzana Koskova at the European Molecular Biology Laboratory in Heidelberg (Germany) and Miguel Hernandez at the University Hospital, Heidelberg. I tried sending an email message to Zuzana Koskova but got no reply. I was unable to find contact information for Miguel Hernandez.

Society for Molecular Biology and Evolution (SMBE) spreads misinformation about junk DNA

The Society for Molecular Biology and Evolution (SMBE) is a pretigious society of workers in the field of molecular evolution. I am a member and I have attended many of their conferences. SMBE sponsors several journals incucluding Genome Biology and Evolution (GBE), which is published by Oxford Academic Press.

The latest issue of GBE has a paper by Stitz et al. (2021) that describes some repetitive elements in the platyhelminth Schistosoma mansoni. The authors conlcude that some of these elements might have a function and this prompts them to begin their discussion with the following sentences.

The days of “junk DNA” are over. When the senior authors of this article studied genetics at their respective universities, the common doctrine was that the nonprotein coding part of eukaryotic genomes consists of interspersed, “useless” sequences, often organized in repetitive elements such as satDNA. The latter might have accumulated during evolution, for example, as a consequence of gene duplication events to separate and individualize gene function (Britten and Kohne 1968; Comings 1972; Ohno 1999). This view has fundamentally changed (Biscotti, Canapa, et al. 2015), and our study is the first one addressing this issue with structural, functional, and evolutionary aspects for the genome of a multicellular parasite.

It is unfortunate that the senior authors didn't receive a good undergraduate education but one might think that they would rectify that problem by learning about genomes and junk DNA before publishing in a good journal devoted to genomes and evolution. Alas, they didn't and, even worse, the journal published their paper with those sentences intact.

As you might imagine, these statements were seized upon by Intelligent Design Creationists who wasted no time in posting on their creationist blog [Oxford Journal: “The Days of ‘Junk DNA’ Are Over ”].

But that's not the worst of it. The same issue contains an editorial written by Casey McGrath who self identifies as a employee of the Society for Molecular Biology and Evolution in Lawrence Kansus (USA). She is the Social Media Editor for Genome Biology and Evolution. The title of her editorial is "Highlight—“Junk DNA” No More: Repetitive Elements as Vital Sources of Flatworm Variation" (McGrath, 2021). She starts off by repeating and expanding upon the words of the senior authors of the study that I referred to above.

“The days of ‘junk DNA’ are over,” according to Christoph Grunau and Christoph Grevelding, the senior authors of a new research article in Genome Biology and Evolution. Their study provides an in-depth look at an enigmatic superfamily of repetitive DNA sequences known as W elements in the genome of the human parasite Schistosoma mansoni (Stitz et al. 2021). Titled “Satellite-like W elements: repetitive, transcribed, and putative mobile genetic factors with potential roles for biology and evolution of Schistosoma mansoni,” the analysis reveals structural, functional, and evolutionary aspects of these elements and shows that, far from being “junk,” they may exert an enduring influence on the biology of S. mansoni.

“When we studied genetics at university in the 1980s, the common doctrine was that the non-protein coding parts of eukaryotic genomes consisted of interspersed, ‘useless’ sequences, often organized in repetitive elements like satellite DNA,” note Grunau and Grevelding. Since then, however, the common understanding of such sequences has fundamentally changed, revealing a plethora of regulatory sequences, noncoding RNAs, and sequences that play a role in chromosomal and nuclear structure. With their article, Grunau and Grevelding, along with their coauthors from Justus Liebig University Giessen, University of Montpellier, and Leipzig University, contribute further evidence to a growing consensus that such sequences play critical roles in evolution.

There's no rational excuse for publishing the Stitz et al. paper with those ridiculous statements and there's no rational excuse for compounding the error by highlighting them in an editorial comment. The Society for Molecular Biology and Evolution should be ashamed and embarrassed and they should issue a retraction and a clarification. They should state clearly that junk DNA is alive and well and supported by so much evidence that it would be perverse to deny it.

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McGrath,C. (2012) Highlight—“Junk DNA” No More: Repetitive Elements as Vital Sources of Flatworm Variation. Genome Biology and Evolution 13: evab217 [doi: 10.1093/gbe/evab217]

Stitz, M., Chaparro, C., Lu, Z., Olzog, V.J., Weinberg, C.E., Blom, J., Goesmann, A., Grunau, C. and Grevelding, C.G. (2021) Satellite-Like W-Elements: Repetitive, Transcribed, and Putative Mobile Genetic Factors with Potential Roles for Biology and Evolution of Schistosoma mansoni. Genome Biology and Evolution 13:evab204. [doi: 10.1093/gbe/evab204]

ENCODE/Junk DNA Fiasco: The IDiots Don't Like Me

Casey Luskin has devoted an entire post to discussing my views on junk DNA. I'm flattered. Read it at: What an Evolution Advocate's Response to the ENCODE Project Tells Us about the Evolution Debate.

Let's look at how the IDiots are responding to this publicity fiasco. Casey Luskin begins with ...

University of Toronto biochemistry professor Larry Moran is not happy with the results of the ENCODE project, which report evidence of "biochemical functions for 80% of the genome." Other evolution-defenders are trying to dismiss this paper as mere "hype".

Yes that's right -- we're supposed to ignore the intentionally unambiguous abstract of an 18-page Nature paper, the lead out of 30 other simultaneous papers from this project, co-authored by literally hundreds of leading scientists worldwide, because it's "hype." (Read the last two or so pages of the main Nature paper to see the uncommonly long list of international scientists who were involved with this project, and co-authored this paper.) Larry Moran and other vocal Internet evolution-activists are welcome to disagree and protest these conclusions, but it's clear that the consensus of molecular biologists -- people who actually study how the genome works -- now believe that the idea of "junk DNA" is essentially wrong.

The biggest mistake in the history of molecular biology (not!)

The creationists are committed to proving that most of our genome is functional because otherwise the idea of an intelligent designer doesn't make a lot of sense. They reject all of the evidence that supports junk DNA and they vehemently reject the notion that 90% of our genome is junk.

I was recently alerted to a video on junk DNA produced by Creation Ministries International in which they quote John Mattick.

A leading figure in genetics, Prof. John Mattick said ...'the failure to recognize the implications of the non-coding DNA will go down as the biggest mistake in the history of molecular biology'.

The creationists are making the common mistake of equating noncoding DNA and junk DNA but the quotation sounded accurate to me since John Mattick makes similar mistakes in his publications. I decided to try and find the exact quotation and reference and the closest I could come to a direct quote was in a paper by Mattick from 2007 (Mattick, 2007). He's referring to introns—here's the exact quotation.

It should be noted that the power and precision of digital communication and control systems has only been broadly established in the human intellectual and technological experience during the past 20–30 years, well after the central tenets of molecular biology were developed and after introns had been discovered. The latter was undoubtedly the biggest surprise (Williamson, 1977), and its misinterpretation possibly the biggest mistake, in the history of molecular biology. Although introns are transcribed, since they did not encode proteins and it was inconceivable that so much non-coding RNA could be functional, especially in an unexpected way, it was immediately and almost universally assumed that introns are non-functional and that the intronic RNA is degraded (rather than further processed) after splicing. The presence of introns in eukaryotic genomes was then rationalized as the residue of the early assembly of genes that had not yet been removed and that had utility in the evolution of proteins by facilitating domain shuffling and alternative splicing (Crick, 1979; Gilbert, 1978; Padgett et al., 1986). Interestingly, while it has been widely appreciated for many years that DNA itself is a digital storage medium, it was not generally considered that some of its outputs may themselves be digital signals, communicated viaRNA.

However, the idea of the biggest mistake in molecular biology predates that reference. Mattick is quoted in a Scientific American article by W. Wayt Gibbs where Gibbs is discssing the "suprising" fact that regulatory sequences are conserved and that some genes are noncoding genes (Gibbs, 2003).

“I think this will come to be a classic story of orthodoxy derailing objective analysis of the facts, in this case for a quarter of a century,” Mattick says. “The failure to recognize the full implications of this—particularly the possibility that the intervening noncoding sequences may be transmitting parallel information in the form of RNA molecules—may well go down as one of the biggest mistakes in the history of molecular biology.”

The discovery of introns in the mid-1970s was definitely a surprise but it's not true, as Mattick implies, that they were immediately assumed to be junk. In fact, as he points out, there was a lot of debate over the possible role of introns in the evolution of protein-coding genes where they could stimulate exon shuffling. Later on, the presence of introns was recognized to be an essential component of alternative splicing.

Once more and more sequences were published it became apparent that neither their size nor their sequences were conserved except for the spliceosome recognition sequences. It soon became obvious that their sequences were evolving at the neutral rate demonstrating that they were mostly junk. Mattick assumes that this conclusion—that introns are mostly junk—is one of the biggest mistakes in molecular biology. I think the opposite is true. I think that the failure of most molecular biologists to understand junk DNA is a huge mistake.

The creationists are misquoting Mattick when they say that the classification of all noncoding as junk is the biggest mistake in molecular biology. In the quotations above, Mattick is specifically referrring to introns but I'm sure he won't be upset to be misquoted in that manner since he firmly believes that most noncoding DNA is functional.

There's a bit of an ironic twist here. If it were true that knowledgeable scientists in the 1970s actually believed that all noncoding DNA was junk then I'd have to agree that this would have been a big (biggest?) mistake. But they didn't and it wasn't a big mistake. As I've said many times, no knowledgeable scientist ever said that all noncoding DNA was junk since they (we) all knew about noncoding genes, regulatory sequences, centromeres, and origins of replication, all of which are functional noncoding DNA. We now know that about 1% of our genome is coding sequences and about 9% is functional noncoding DNA. The other 90% is junk.

[Stop Using the Term "Noncoding DNA:" It Doesn't Mean What You Think It Means]

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Mattick, J.S. (2007) A new paradigm for developmental biology. Journal of Experimental Biology 210:1526-1547. [doi: 10.1242/jeb.005017]

Gibbs, W.W. (2003) The unseen genome: gems among the junk. Scientific American 289:46-53.

James Shapiro doesn't like junk DNA

Shapiro doubles down on his claim that junk DNA doesn't exist.

It's been a while since we've heard from James Shaprio. You might recall that James A. Shapiro is a biochemistry/microbiology professor at the University of Chicago and the author of a book promoting natural genetic engineering. I reviewed his book and didn't like it very much—Shapiro didn't like my review [James Shapiro Never Learns] [James Shapiro Responds to My Review of His Book].