BREAKING NEWS: Intelligent Design Creationists claim that this year's Nobel Prize refutes junk DNA and confirms IDC predictions!

This is a Come Let Us Reason Together (sic) podcast moderated by Lenny Esposito with Faxale "Fuz" Rana of Reasons to Believe and Casey Luskin of the Discovery Institute. They discuss this year's Nobel Prize for the discovery of microRNAs and "how it supports intelligent design and weakens the evolutionary paradigm." Casey Luskin devoted a post to the topic on the Discovery Institute propaganda blog: 2024 Nobel Prize Awarded for the Discovery of Function for a Type of “Junk DNA”.

Enjoy! (Spot the lies.¹)

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1. In Luskin's case, we know he is lying. [Is Casey Luskin lying about junk DNA or is he just stupid?]

William Haseltine misrepresents molecular biology and calls for a paradigm shift

William Hasletine is a well-respected molecular biologist with an outstanding track record dating back to the time when he was a graduate student under Jim Watson and Wally Gilbert where he studied the regulation of gene expression in bacteria (Ph.D. in 1973). This is why I was surprised to see his recent article in Forbes where he seems to have fallen hook-line-and-sinker for postgenomics gobbledygook. It looks like Haseltine is losing the ability to think critically as he concentrates more on technology and public policy.

A New Dogma Of Molecular Biology: A Paradigm Shift by William A. Haseltine

The "wisdom" of the Discovery Institute

John G. West is Vice President of the Discovery Institute and one of the founding members of the Center for Science and Culture. He is a leading proponent of Intelligent Design Creationism.

West has reviewed the latest book by Francis Collins; the review was published in The Federalist. [Francis Collins’ Latest Book Doubles Down On His Massive Abuses Of Power]

Science journal tries to understand misinformation

The November 1, 2024 issue of Science contains three articles on misinformation in science. The articles tend to concentrate on the standard examples such as vaccine misinformation but there's another kind of misinformation that's just as important. I'm talking about scientific misinformation that's spread by journals like Science and Nature.

Do any of you remember the arsenic affair? That's when science accepted a paper by Felisa Wolfe-Simon and her collaborators claiming that they isolated a bacterium that substituted arsenic for phosphorus in its DNA. The paper was published online and was severely criticized after a ridiculous NASA press conference. It was eventually refuted when Rosie Redfield and others looked closely at the bacterial DNA and showed that it did not contain arsenic. The paper has still not been retracted. [See Reviewing the "Arseniclife" Paper.]

And let's not forget the massive misinformation campaign associated with the publication of ENCODE results in 2012.

Do plants have junk DNA?

Current Opinion in Plant Biology has a special edition devoted to Genome studies and molecular genetics 2024. The only paper (so far) that discusses plant genomes is one devoted to RNAs. Here's the abstract ...

Anyatama, A., Datta, T., Dwivedi, S. and Trivedi, P.K. (2024) Transcriptional junk: Waste or a key regulator in diverse biological processes? Current Opinion in Plant Biology 82:102639. [doi: 10.1016/j.pbi.2024.102639]

Plant genomes, through their evolutionary journey, have developed a complex composition that includes not only protein-coding sequences but also a significant amount of non-coding DNA, repetitive sequences, and transposable elements, traditionally labeled as “junk DNA”. RNA molecules from these regions, labeled as “transcriptional junk,” include non-coding RNAs, alternatively spliced transcripts, untranslated regions (UTRs), and short open reading frames (sORFs). However, recent research shows that this genetic material plays crucial roles in gene regulation, affecting plant growth, development, hormonal balance, and responses to stresses. Additionally, some of these regulatory regions encode small proteins, such as miRNA-encoded peptides (miPEPs) and microProteins (miPs), which interact with DNA or nuclear proteins, leading to chromatin remodeling and modulation of gene expression. This review aims to consolidate our understanding of the diverse roles that these so-called “transcriptional junk” regions play in regulating various physiological processes in plants.

Philip Ball's view of alternative splicing

Genomics is a powerful tool that allows you to collect massive amounts of data that can point the way to new understanding. But it can also be abused when the results are overinterpreted. We saw an extraordinary example of this in 2012 when ENCODE made unsubstantiated claims that were quickly challenged.

I'm reminded of the caution from Sydney Brenner who warned us about genomics (Brenner, 2000) and the warning in Dan Graur's harsh critique of the 2012 ENCODE claims (Graur et al., 2013) where they said ...

The Editor-in-Chief of Science, [Bruce Alberts,] has recently expressed concern about the future of "small science," given that ENCODE-style Big Science grabs the headlines that decision makers so dearly love. Actually the main function of Big Science is to generate massive amounts of easily accessible data. The road from data to wisdom is quite long and convoluted. Insight, understanding, and scientific progress are generally achieved by "small science." ...

Three lungfish species have huge genomes

Lungfish are our closest living fish cousins. All living terrestrial vertebrates (e.g. amphibians, mammals, reptiles) descent from a common ancestor with lungfish. The split occurred about 400 million years ago (4Ma) (Devonian) when there were 70-100 different lungfish species.

This relationship (lungfish-tetrapods) was firmly established recently by comparing the genome of the Australian lungfish (Neoceratodus forsteri) with that of tetrapods (Meyer et al., 2021). The other possibility had been ceolacanth-tetrapods. Coelacanths and lungfish are related—they form the class Sarcopterygii (lobe-finned fish).

Santi Garcia-Vallvé reviews my book

Santi Garcia-Vallvé has reviewed my book in the journal Mètode. It's written in Catalan but Santi was kind enough to send me a translation.

OUR GENOME HAS NOT YET SPOKEN ITS LAST WORD

What's in Your Genome? 90% of Your Genome Is Junk. Laurence A. Moran. Aevo University of Toronto Press (UTP). May 2023. 392 pages.

What's in Your Genome? exposes a variety of topics and concepts in molecular biology, genetics, and evolution that have been misunderstood by scientists and the general public. Many of these concepts are widely accepted, despite ongoing debate about them. Although the author, Larry Moran, has exhaustively discussed most of these issues on his blog "Sandwalk: Strolling with a sceptical biochemist", discussing them in a book allows for a more in-depth investigation.

One of these recurring themes is Francis Crick 's 1957 proposal of the Central Dogma of Molecular Biology. In his book Molecular Biology of the gene, James Watson adapted this concept by summarizing in a figure the flow of genetic information from DNA to RNA and then to proteins. This version was widely adopted, and many scientists now assume that it was the original definition. However, Crick claimed that once the information had been transferred to the proteins, it could not be returned to nucleic acids. Other controversial topics discussed in the book include the number of genes encoded in the human genome, the concept of Junk DNA and the prevalence of alternative splicing in the transcription of the human genome. Larry takes a certain viewpoint on all these problems, as evidenced by the title of the book, but he also presents arguments from all sides. Throughout the book, he argues that scientists must present evidence in support of and against their findings, as well as contextualise their discoveries in light of the knowledge of the subject. Thus, the first chapters of the book describe in depth the basic ideas of genetics, genetics and evolution that are required to understand the arguments that he will present later, showing also when and how they were discovered.

This is a highly recommendable book that pushed us to think about how research findings are explained and the importance of placing them in their proper context. The media frequently looks for stunning headlines and there is growing demand to assess the social impact of a project, article or scientific project. However, if we exaggerate our findings, we risk exacerbating further diminishing the general lack of interest in scientific news. Everyone is responsible that this does not happen.

Santi Garcia-Vallvé is an associate professor in the Department of Biochemistry and Biotechnology at Rovira i Virgili University (URV) in Tarragona, Spain, and a member of the Chemoinformatics and Nutrition research group."

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Philip Ball doesn't understand sloppy genomes

... anything found to be true of E.coli must also be true of Elephants.
                                                         Jacques Monod (1961)

This version of the famous statement by Jacques Monod comes from 1961 but he said similar things much earlier and other scientists even predate Monod's earliest use of the phrase (Friedman, 2004). He echoed this same idea in Chance and Necessity (p. 102)

The diversity of types remained even so, and there was no getting around the fact that a great many macroscopic structural patterns, radically unlike one another, coexist in the biosphere. A blue alga, an infusorium, an octopus, and a human being—what had they in common? With the discovery of the cell and the advent of cellular theory a new unity could be seen under this diversity. But it was some time before advances in biochemistry, mainly during the second quarter of this century, revealed the profound and strict oneness, on the microscopic level, of the whole of the living world. Today we know that from a bacterium to man the chemical machinery is essentially the same, in both its structure and its functioning.

Monod was making a case for life as a chemical process and he reflected the view of the 'phage group who were studying bacteria and bacteriophage. He argued that all living things would consist of the same basic chemicals such as lipids, nucleic acids, proteins, and carbohydrates. He also assumed that all living things would have similar networks of metabolic enzymes and contain similar pathways. These enzymes would be regulated by similar mechanisms, such as allosteric regulation, and they would be composed of the same 20 amino acids. He expected all living cells would have similar mechanisms for capturing energy and they would obey the fundamental laws of thermodynamics.

He assumed that the genetic code would be universal and that the process of protein synthesis would be essentially the same in all species. He assumed that the fundamentals of transcription and DNA replication would be the same in all species. He imagined that the basic principles of gene regulation that were worked out in bacteria would apply to eukaryotes. This included the action of transcription factors and more unusual regulatory molecules such as the regulatory RNAs discovered in 'phage and bacteria. He expected that genes, regulatory sequences, origins of replication, and other important genetic elements would be found in the DNA molecules of the genome.

This theme of unity of life at the microscopic level was very important but it did not mean that all living things would be identical. Monod was a firm proponent of evolution and since evolution depended on the random occurrence of mutations the actual history of life is unpredictable. There's nothing profoundly upsetting about the fact that elephants have trunks and E. coli doesn't because that's not the point.

I'm sure that Monod was not upset to learn that some genes had introns or that eukarotic chromatin is more complicated than the DNA-protein complexes found in bacteria. He would not have been shocked to learn that many eukaryotes have more functional RNAs than E. coli or bacteriophage λ. Junk DNA was not a problem for someone who understood evolution.

I think Monod reflected the dominant view of most knowledgeable biochemists and molecular biologists of the 1960s and 1970s.

Over the next 50 years we learned a lot more about complex eukaryotes and the dominant theme at the molecular level is that they contain lots of junk DNA and lots of overly complex structures that only make sense in light of evolution. There's a lot of sloppiness in eukaryotes, including genomes full of transposon fossils, aberrant transcription, pseudogenes, inefficient splicing, and promiscuous enzymes. A lot of this sloppiness was apparent in the 1970s, including the fact that junk DNA must contain thousands of ineffective transcription factor binding sites. We learned in the 1980s that some structures, such as the spliceosome, could only have arisen by evolution since no designer in their right mind would have built such a thing.

I would be quite proud to have served on the committee that designed the E. coli genome. There is, however, no way that I would admit to serving on a committee that designed the human genome. Not even a university committee could botch something that badly.                                                          David Penny

I got this quote from Dan Graur who credits it to David Penny as a personal communication. Graur used it in his scathing criticism of ENCODE researchers after they declared the death of junk DNA (Graur et al., 2013). The meaning is clear. The E. coli genome is compact and carries all the information needed to ensure the survival and evolution of the bacterium. It has one copy of most protein-coding genes, two copies of ribosomal RNA genes, and a minimal number of tRNA genes. The regulatory sequences are just big enough for efficient transcription under the appropriate conditions. Many genes are clustered in operons to save space. There's only one origin of replication and one terminator sequence. There's only one chromosome and it is efficiently segregated to each daughter cell after DNA replication and cell division. There are only a small number of regulatory RNA genes in E. coli.

The human genome is a mess. 90% of it is junk and it requires complicated features like centromeres and telomeres. There are 100,000 origins of replication and tens of thousands of pseudogenes. The protein-coding genes are full of useless introns and they take up 40% of the genome even though the functional parts only occupy 1%. Every cell has thousands of incorrectly spliced transcripts. The genome is littered with fossil transposons and viruses and many of them still have partially active promoters churning out junk RNA. Useless transcription factor binding sites and chromatin alterations are ubiquitous. The abundance of junk DNA means that you need tens of thousands of copies of every transcription factor just to make sure the right genes are regulated. A large part of the genome is transcribed but the vast majority of those transcripts are useless junk.

This is why David Penny would not be proud to have served on the committee that designed the human genome. Neither would I, and that's why I spent so much time explaining sloppy genomes in my book. The idea of a sloppy genome is a difficult concept to grasp so I devoted the final chapter (Chapter 11) to the art of coping with this issue.

Now let's look at how Philip Ball handles this information on pages 116-117 of his book How Life Works.

These differences in the relative proportions of coding and non-coding DNA for simpler and more complex organisms reflect fundamental distinctions in how these organisms work. The problem has been delightfully, if inadvertently, stated by theoretical biologist David Penny. "I would be quite proud to have served on the committee that designed the E. coli genome" he has said. "There is, however, no way that I would admit to serving on a committee that designed the human genome. Not even a university committee could botch something that badly."

I'd suggest that can be rephrased: "I can understand how the E. coli genome works. I cannot make any sense of how the human genome works." So the corollary of Penny's comment is rather profound: how E. coli works is not how humans work. But his quip betrays an understandable frustration that the workings of the human genome are inscrutable to us. And I fear that the remark carries the same bias as that which leads us to insist that a foreign language we find difficult to learn is unnecessarily perverse and even absurd.

This shift in perspective challenges a famous statement by Jacques Monod: "What is true for E. coli is true for the elephant." In fairness, Monod had in mind here the notion of how DNA encodes proteins—for indeed it does so in (roughly) the same way in bacteria as in pachyderms, insofar as it uses the same genetic code. But the implication in Monod's comment is that this is what really matters in the same spirit as Crick's Central Dogma. We can now see that Monod's quote is misleading in an important sense, because what matters for E. coli is not the same as what matters for an elephant. The bacterium has a genome dedicated mostly to making proteins. The elephant has a genome dedicated mostly to making noncoding RNAs with regulatory functions. To truly understand how the elephant—and the human—works, we need to untangle the mechanisms governing this regulation.

As Morris and Mattick say,

It appears that we may have fundamentally misunderstood the nature of the genetic programming in complex organisms because of the assumption that most genetic information is transacted by proteins. This may be largely true in simpler organisms, but is turning out not to be the case in more complex organisms, whose genomes appear to be progressively dominated by regulatory RNAs that orchestrate the epigenetic trajectories of differentiation and development.

Or as biochemist Danny Licatalosi and neuroscientist Robert Darnell put it, biological complexity "has RNA at its core."

I think this is an excellent illustration of the differing viewpoints of Philip Ball and many biochemists and molecular biologists. David Penny and the rest of us don't disparage the human genome because we don't understand it. Quite the contrary. We think we DO understand evolution and the basic principles of molecular biology and that's why we recognize a sloppy genome when we see it. Philip Ball just can't get his head around the fact that we aren't ignorant of functional non-coding RNAs ... we just don't believe Mattick and ENCODE when they claim, without evidence, that the human genome is full of non-coding genes modulating some sophisticated regulation of the protein-coding genes.

Not only does such a model lack support but it doesn't make any sense. Why would all the 10,000 or so housekeeping genes require such regulation in humans and not in yeast? Why would evolution have selected for regulatory RNAs acting on the genes for the glycolytic enzymes? What kind of selective advantage would there have to be in order to evolve a regulatory RNA gene that could tweek expression by a few percent?

"Ball is one of the most meticulous, precise science writers out there. He is the antithesis of hypey, "dumb-it-down" reporting. He is MUCH more credible than you are, Laurence."

John Horgan July, 2024Philip Ball even wants to twist the Monod quote to fit his agenda on the importance of proteins. That's not what Monod meant. But let's think about this for a minute. The biochemists of the last century discovered a complex network of metabolic pathways with reactions that were catalyzed almost exclusively by protein enzymes. That hasn't changed. It's true of E. coli and it's true of elephants.

They also discovered that the expression of genes, especially at the level of transcription, was mostly controlled and regulated by proteins; namely, RNA polymerase and transcription factors. That hasn't changed. The expression of elephant and human genes is also regulated by transcription factors and RNA polymerase. Hundreds of studies of particular mammalian genes have demonstrated beyond a doubt that we can explain most regulation by such a model.

That doesn't mean that proteins are the only players in regulation. Over the past several decades we've discovered a variety of regulatory RNAs and we now know that there are more of these non-coding genes in humans than in bacteria. We don't know how many but so far the number of well-characterized examples amounts to fewer than 2000 genes and probably less than 1000. Note that I said "well-characterized" examples and that means that the individual RNA molecule has been studied and its biologically relevant function has been confirmed. That's not the same as a genomics study that simply identifies candidate transcripts that may or may not have a function.

Proteins still play the most important functional roles in metabolism and gene expression but they are not the only players. We've known that for 50 years. The only thing that's changed is that there may be as many as two thousand non-coding genes in humans and only a dozen or so in E. coli and the human genome may be a lot more sloppy than bacterial genomes. That's not a paradigm shift.

Note: Philip Ball was an editor at Nature and that's ironic because it's the failure of Nature editors to do their job in 2012 that got us into the mess we're in today. The editors not only allowed ENCODE researchers to make exaggerated claims about junk DNA but they actively supported and participated in the publicity campaign that sold those false claims to the general public. Nature editors have never apologized for their behavior in 2012; in fact, one of them, Magdalena Skipper, has been promoted to editor-in-chief. [The 10th anniversary of the ENCODE publicity campaign fiasco]

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Friedman, H.C. (2004) From Butyribacterium to E. coli: An Essay on Unity in Biochemistry. Perspectives in Biology and Medicine 47:47-66. doi: 10.1353/pbm.2004.0007

Graur, D., Zheng, Y., Price, N., Azevedo, R.B., Zufall, R.A. and Elhaik, E. (2013) On the immortality of television sets:“function” in the human genome according to the evolution-free gospel of ENCODE. Genome Biology and Evolution 5:578-590. doi: doi: 10.1093/gbe/evt028

Philip Ball strikes back

Philip Ball believes that we are in the middle of a revolution in our way of thinking about how life works. His ideas are complex but part of his case involves molecular biology and how things work at the molecular level. Ball believes that the old view of molecular biology placed far too much emphasis on coding DNA and ignored all the other functional regions of genomes. He also says that most of our genes specify non-coding RNA instead of mRNA and implies to his readers that a very large fraction of our genome is functional (i.e. not junk).¹

In order to build the case for revolution, he tries to demonstrate a paradigm shift in our view of molecular biology by showing a huge gap between the understanding of previous generations of molecular biologists and the post-genomic view. I believe he is wrong about this for two reasons: first, he misrepresents the views of older molecular biologists and, second he misrepresents the discoveries of the past twenty years. I tried to explain why he was wrong about these two claims in a previous post where I discussed an article he published in Scientific American in May 2024: Philip Ball says RNA may rule our genome.

Philip Ball responded to my criticism in a comment under that article.

Older molecular biologists were really stupid

I said ...

Ball begins with the same old myth that writers like him have been repeating for many years. He claims that before ENCODE most molecular biologists were really stupid. According to Philip Ball, most of us thought that coding DNA was the only functional part of the genome and most of the rest was junk DNA.

In the comment section of my earlier post, Philip Ball says,

I’m sorry to say that Larry’s commentary here is dismayingly inaccurate.

Let’s get this one out of the way first:

“He claims that before ENCODE most molecular biologists were really stupid.”

I have never made this claim and never would – it is a pure fabrication on Larry’s part. I guess this is what John Horgan meant in his comment to Larry: credible writers don’t just make up stuff.

I admit that Philip Ball never said those exact words. I'll leave it to the readers to decide whether my characterization of his position is accurate.

I stand by the statements I made although I admit to a bit of hyperbole. Ball has said repeatedly that the molecular biologists of my generation were wedded to the idea that coding regions were the only important part of the genome and he often connects that to the Central Dogma of Molecular Biology. He also claims that the experts in molecular biology dismissed all non-coding DNA as junk. Here's how he puts it in another article that he published recently in Aeon: We are not machines.

Only around 1-2 per cent of the entire human genome actually consists of protein-coding genes. The remainder was long thought to be mostly junk: meaningless sequences accumulated over the course of evolution. But at least some of that non-coding genome is now known to be involved in regulating genes: altering, activating or suppressing their transcription in RNA and translation into proteins.

I interpret that to mean that older molecular biologists, like me, didn't know about functional non-coding DNAs such as centromeres, telomeres, origins of replication, non-coding genes, SARs, and regulatory sequences in spite of the fact that thousands of papers on these sequences were published in the 30 years that preceded the publication of the first draft of the human genome sequence. This is not true, we did know about those things. I don't think it's too much of an exaggeration to say that Philip Ball thinks we were really stupid.

Here's what he says in his book, "How Life Works" (p. 85) when he's talking about the beginning of the human genome project.

Even at its outset, it faced the somewhat troubling issue that just 2 percent or so of our genome actually accounts for protein-coding genes. The conventional narrative was that our biology was all about proteins, for each of which the genome held the template. ... But we had all this other DNA too! What was it for? The common view was that it was mostly just junk, like the stuff in our attics: meaningless material accumulated during evolution, which our cells had no motivation to clear out.

Again, his claim is that in 1990 at the beginning of the human genome project the experts in molecular biology thought that non-coding DNA was mostly junk (98% of the genome). I have repeatedly refuted this myth and challenged anyone to come up with a single scientific paper arguing that all non-coding DNA is junk. I challenge Philip Ball to find a single molecular biology textbook written before 1990 that fails to discuss regulation, non-coding genes, and other non-coding functional elements in the human genome.

The truth is that the molecular biology experts concluded in the 1970s that we had about 30,000 genes and that 90% of our genome is junk and 10% is functional. That 10% consisted of about 2% coding DNA (now thought to be only 1%) and 8% functional non-coding DNA. So the "conventional narrative" was that there was a lot more functional non-coding DNA than coding DNA.

The human genome is full of genes for regulatory RNAs.

"Ball is one of the most meticulous, precise science writers out there. He is the antithesis of hypey, "dumb-it-down" reporting. He is MUCH more credible than you are, Laurence."

John Horgan July, 2024The title of the article I was discussing is "Revolutionary Genetics Research Shows RNA May Rule Our Genome." In that article Ball says that ENCODE was basically right and there are many more non-coding genes than protein-coding genes. I pointed out that Ball mentions some criticism of this idea but only to dismiss it. I said that "[Ball] wants you to believe that almost of all of those transcripts are functional—that's the revolution that he's promoting." Philip Ball objects to this statement ...

This too is sheer fabrication. I don’t say this in my article, nor in my book. Instead, I say pretty much what Larry seems to want me to say, but for some reason he will not admit it – which is that there is controversy about how many of the transcripts are functional."

Ball states that "ENCODE was basically right" when they claimed that 75% of our genome was transcribed and he goes on to say that ...

Dozens of other research groups, scoping out activity along the human genome, also have found that much of our DNA is churning out 'noncoding' RNA.

He says that ENCODE has identified 37,000 noncoding genes but there may be as many as 96,000. After making these definitive statements, he mentions that there are "still doubters" but then discuss why these discoveries are revolutionary. Later on he quotes John Mattick suspecting that there may be more that 500,000 non-coding genes.

Toward the end of the article, after discussing all kinds of functional RNAs, he brings up the Ponting and Haerty review where they say that most lncRNAs are just noise. He also mentions that the low copy number of non-coding RNAs raises questions about whether they are functional but immediately counters with the standard excuses from his allies.

Ball closes the article with ...

Gingeras says he is perplexed by ongoing claims that ncRNAs are merely noise or junk, as evidence is mounting that they do many things. "It is puzzling why there is such an effort to persuade colleagues to move from a sense of interest and curiosity in the ncRNA field to a more dubious and critical one," he says.

Perhaps the arguments are so intense because they undercut the way we think our biology works. Ever since the epochal discovery about DNA's double helix and how it encodes information, the bedrock idea of molecular biology has been that there are precisely encoded instructions that program specific molecules for particular tasks. But ncRNAs seem to point to a fuzzier, more collective, logic to life. It is a logic that is harder to discern and harder to understand. ut if scientists can learn to live with the fuzziness, this view of life may turn out to be more complete.

What's remarkable about the quote from a leading ENCODE worker (Gingeras) is that he is "puzzled" by scientists who are dubious and critical about claims in the ncRNA field. Isn't that what good scientists are supposed to do? Isn't that exactly what we did when we successfully challenged the dubious claims about junk DNA made in 2012?

There is no doubt in my mind that Philip Ball has fallen hook-line-and-sinker for the ENCODE claims that our genome is buzzing with non-coding genes. He only brings up the counter-arguments to dismiss them and pretend that he is being fair. Nobody who was truly skeptical about the function of transcripts would write an article with the title, "Revolutionary Genetics Research Shows RNA May Rule Our Genome."

However, as Ball points out in other comments, he does have a sentence in his book where he mentions that perhaps only 30% of the genome is functional. He says in the comment that what he believes is that the amount of functional DNA lies somewhere between 10% and 30%. That's not something that he mentions in the Scientific American article but, if he's being honest, it does mean that I was unfair when I said he believes that "almost of all of those transcripts are functional" but I only know that from what he now says, not from the published article.

If I were to take Philip Ball at his word—as expressed in the comment—then he must believe that most of the ENCODE transcripts are junk RNA. That's not a belief that you get from reading his published work.² Furthermore, if I were to take him at his word, then he must believe that there are some reasonable criteria that must be applied to a transcript in order to decide whether it has a biologically relevant function. So, when he says that ENCODE identified 37,600 non-coding genes he must have these criteria in mind but he doesn't express any serious skepticism about that number. We all know that there's no solid evidence that such a large number of transcripts are functional but that doesn't bother Philip Ball. He thinks we are in the middle of an RNA revolution.

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1. In commenting to my previous post, Ball says he believes that somewhere between 70% and 90% of our genome is junk but he doesn't say this in the Scientific American article. Instead, he says that scientists were surprised to learn that 75% of the human genome is transcribed implying that there's a lot of function. He goes on the say that "ENCODE was basically right." But what the ENCODE publicity campaign actually said was that junk DNA is dead and there's practically no junk DNA. If Ball really believes that up to 90% of the genome is junk then to me this means that ENCODE was spectacularly wrong not "basically right."

2. Ball says that 75% of the genome is transcribed. If Ball believes that as little as 10% may be functional then he must believe that less than 10% is transcribed to produce functional RNAs since he has to allow for regulatory sequences and other functional DNA elements. Let's say that 8% is a reasonable number. Ball seems to be willing to admit that 67% of the genome might be transcribed to produce junk RNA.

Philip Ball says RNA may rule our genome

Philip Ball is on a roll. He has published a new book plus several articles in popular magazines and he has appeared in a bunch of podcasts and YouTube videos. The message is all the same, he claims that it's time for a revolution in biology.

Ball's ideas are complicated and I won't go into all of them in this article. Instead, I want to focus on one of his more scientific claims; namely, the claim that genomic data has overthrown the fundamental principles of molecular biology. Let's look at his recent (May 14, 2024) article in Scientific American: Revolutionary Genetics Research Shows RNA May Rule Our Genome.¹

The subtile of the article is "Scientists have recently discovered thousands of active RNA molecules that can control the human body" and that's the issue that I want to discuss here.

Jonathan Wells (1942 - 2024)

Johnathan Wells died recently. He was a well-known Intelligent Design Creationist and that's why Evolution News (sic) is eulogizing him by posting multiple tributes and excerpts from his books and essays.

I think it's only fair to post links to my efforts to demonstrate the serious flaws in his arguments. I'm particularly proud of the series of articles I wrote when he published his book The Myth of Junk DNA. I went through every chapter and analyzed his arguments against junk DNA. It won't surprise anyone to learn that I found those arguments lacking in substance and in some cases I discovered that Wells had misrepresented the science.

Here are my posts.

• Jonathan, Moonies, and Junk DNA
• Junk & Jonathan: Part I—Getting the History Correct
• Junk & Jonathan: Part 2— What Did Biologists Really Say About Junk DNA?
• Junk & Jonathan: Part 3—The Preface
• Junk & Jonathan: Part 4—Chapter 1
• Junk & Jonathan: Part 5—Chapter 2
• Junk & Jonathan: Part 6—Chapter 3
• Junk & Jonathan: Part 7—Chapter 4
• Junk & Jonathan: Part 8—Chapter 5
• Junk & Jonathan: Part 9—Chapter 6
• Junk & Jonathan: Part 10—Chapter 7
• Junk & Jonathan: Part 11—Chapter 8
• Junk & Jonathan: Part 12—Chapter 9
• Junk & Jonathan: Part 13—Chapter 10

Jonathan Wells never responded directly to my criticism but he did respond to a comment that Paul McBride made on one of his blog posts. Paul asked him why he didn't respond to my post and here's what Wells said,

Oh, one last thing: “paulmc” referred to an online review of my book by University of Toronto professor Larry Moran—a review that “paulmc” called both extensive and thorough. Well, saturation bombing is extensive and thorough, too. Although “paulmc” admitted to not having read more than the Preface to The Myth of Junk DNA, I have read Mr. Moran’s review, which is so driven by confused thinking and malicious misrepresentations of my work—not to mention personal insults—that addressing it would be like trying to reason with a lynch mob.

This is typical of the attitude of most Intelligent Design Creationists. They are happy to publish lengthy books denegrating science and scientists but couldn't be bothered responding to criticism.

Here's are some other post of mine where I demonstrate the flawed thinking of Jonathan Wells.

• Jonathan Wells talks about junk DNA
• Jonathan Wells illustrates zombie science by revisiting junk DNA
• Brace yourselves, a new "Icons" is coming
• Jonathan Wells proves that life must have been created by gods
• Answering ten questions from the IDiots
• John Mattick vs. Jonathan Wells
• Some Questions for IDiots
• American Loons: #409 Jonathan Wells and #411 John West
• A Dishonest Intelligent Design Proponent?
• We Called Out IDiot Jonathan Wells, and He Folded
• Jonathan Wells Sends His Regrets
• Watch Jonathan Wells Screw Up
• Jonathan Wells Talks About Sequence Conservation
• Ohmygod! These photographs are faked!
• Fossil Horses and Directed Evolution
• Peppered Moths and the Confused IDiots
• Jonathan Wells reviews the Christiane Nüsslein-Volhard and Wieschaus Experiment

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John Mattick's seminar at the University of Toronto

I just learned that John Mattick gave a seminar this morning at the Department of Cell & Systems Biology at the University of Toronto. Unfortunately, I was unable to attend.

Most Sandwalk readers will recognize Mattick as one of the few remaining vocal opponents of junk DNA. He is probably best known for his dog-ass plot but this is only one of the ways he misrepresents science.

Scite Assistant (AI) answers the question "How much of the human genome consist of junk DNA?"

Scite Assistant is billed as "your AI research partner" and as "ChatGPT for researchers." It's supposed to draw on peer-reviewed published scientific papers for its information and it will give you an answer with genuine citations.

That sounds like a good idea until you realize that the scientific literature is full of misinformation and conflicting information. What we need is an AI assistant that can help us sort throught the misinformation and give us a genuine well-informed answer on controversial issues.

Let's pick the question of junk DNA as a completley random (!) example of such an issue. The scientific literature is full of false information about the origin of the term "junk DNA" and what it was originally intended to describe. It's also full of false information about recent results and how they pertain to junk DNA.

Zach Hancock explains junk DNA

Zach Hancock is a postdoc in ecology & evoluvionary biology at the University of Michigan. He has a YouTube channel with several thousand subscribers. You might recall that he interviewed me last year when my book came out [Zach Hancock interviews me on his YouTube channel].

He has just posted a new video on junk DNA that's well worth watching. He tries to correct all the falsehoods and misinformation on junk DNA, especially those promoted by creationists. It's well worth watching.

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Is Casey Luskin lying about junk DNA or is he just stupid?

I'm going to address a recent article by Casey Luskin on Evolution News (sic) and a podcast on a Current Topics in Science podcast produce by Christ Jesus Ministries. But first, some background.

A recent paper in Nature looked at a region on chromosome 21 where mutations associated with autoimmune and inflammatory disease were clustered. This region did not contain any known genes and is referred to in the paper as a "gene desert." The authors reasoned that it probably contained one or more regulatory sites and, as expected, they were able to identify an enhancer element that helps control expression of a nearby gene called ETS2 (Stankey et al., 2024).

The results were promoted in a BBC article: The 'gene deserts' unravelling the mysteries of disease. The subtitle of the article tells you where this is going, "Mutations in these regions of so-called "junk" DNA are increasingly being linked to a range of diseases, from Crohn's to cancer." The article implies that since only 2% of the human genome codes for proteins the remaining 98% "has no obvious meaning or purpose." The caption to one of the figures says, "Gene deserts are regions of so-called genetic "junk" that do not code for proteins – but they may play an important role in disease." Thus, according to the BBC, the discovery of a regulatory sequence conflicts with the idea of junk DNA.

There's no mention of junk DNA in the original Nature article and none of the comments by the senior author (James Lee) in the BBC article suggest that he is confused about junk DNA.

An article published in Nature Communications looked at expression of human endogenous retrovirus elements (HERV's) in human brain. The authors found that expression of two HERV sequences is associated with risk for schizophrenia but the authors noted that is wasn't clear how this expression played a role in psychiatric disorders (Duarte et al., 2024)

Although the term "junk DNA" was not mentioned in the original article, the press release from King's College, London makes the point that HERVS were assumed to be junk DNA. The implication is that this is one of the first publications to discover a possible function for this junk DNA. (Functional elements derived from HERVs have been known for three decades.)

Casey Luskin wrote about these studies yesterday in an article on the intelligent design website: Disease-Associated “Junk” DNA Is Evidence of Function and talks about it in the podcast that I link to below.

Luskin continues to promote the false claim that all non-coding DNA was assumed to be junk. That allows him to highlight all studies that discover new functional elements in non-coding DNA and claim that it refutes junk DNA. He's been doing this for years in spite of multiple attempts to correct him. Therefore, the answer to the question in the title in obvious, he is a liar—judge for yourselves whether he is also stupid.

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Duarte et al. (2024) Integrating human endogenous retroviruses into transcriptome-wide association studies highlights novel risk factors for major psychiatric conditions. Nature Communications 15: 3803 [doi: 10.1038/s41467-024-48153-z]

Stankey et al. (2024) A disease-associated gene desert directs macrophage inflammation through ETS2. Nature 630: 447–456 [doi: 10.1038/s41586-024-07501-1]

"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.

Tom Cech writes about the "dark matter" of the genome

Tom Cech won a Nobel Prize for discovering one example of a catalytic RNA. He recently published an article in the New York Times extolling the virtues of RNA and non-coding genes [The Long-Overlooked Molecule That Will Define a Generation of Science]. There's a fair amount of hype in the article but the main point is quite valid—over the past fifty years we have learned about dozens of important non-coding RNAs that we didn't know about at the beginning of molecular biology [see: Non-coding RNA, Non-coding DNA].

The main issue in this field concerns the number of non-coding genes in the human genome. I cover the available data in my book and conclude that there are fewer than 1000 (p.214). Those scientists who promote the importance of RNA (e.g. Tom Cech) would like you to believe that there are many more non-coding genes; indeed, most of those scientists believe that there are more non-coding genes than coding genes (i.e. > 20,000). They rarely present evidence for such a claim beyond noting that much of our genome is transcribed.

Tom Cech is wise enough to avoid publishing an estimate of the number of non-coding genes but his bias is evident in the following paragraph from near the end of his article.

Although most scientists now agree on RNA's bright promise, we are still only beginning to unlock its potential. Consider, for instance, that some 75 percent of the human genome consists of dark matter that is copied into RNAs of unknown function. While some researchers have dismissed this dark matter as junk or noise, I expect it will be the source of even more exciting breakthroughs.

Let's dissect this to see where the bias lies. The first thing you note is the use of the term "dark matter" to make it sound like there's a lot of mysterious DNA in our genome. This is not true. We know a heck of a lot about our genome, including the fact that it's full of junk DNA. Only 10% of the genome is under purifying selection and assumed to be functional. The rest is full of introns, pseudogenes, and various classes of repetitive sequences made up mostly of degraded transposons and viruses. The entire genome has been sequenced—there's not much mystery there. I don't know why anyone refers to this as "dark matter" unless they have a hidden agenda.

The second thing you notice is the statement that 75% of the genome is transcribed at some time or another and, according to Tom Cech, these transcripts have an unknown function. That's strange since protein-coding genes take up roughly 40% of our genome and we know a great deal about coding DNA, UTRs, and introns. If you add in the known examples of non-coding genes, this accounts for an additional 2-3% of the genome.¹

Almost all the rest of the transcripts come from non-conserved DNA and those transcripts are present at less than one copy per cell. As the ENCODE researchers noted in 2014, they are likely to be junk RNA resulting from spurious transcription. I'd say we know a great deal about the fraction of the genome that's transcribed and there's not much indication that it's hiding a plethora of undiscovered functional RNAs.

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Photo credit: University of Colorado, Boulder.

1. In my book I make a generous estimate of 5,000 non-coding genes in order to avoid quibbling over a smaller number and in order to demonstrate that even with such a obvious over-estimate the genome is still 90% junk.

Junk DNA debate: Casey Luskin vs Dan Stern Cardinale

Here's a link to the junk DNA debate between Dan Stern Cardinale and Casey Luskin. The debate took place on May 2, 2024.

I mentioned in a previous post that Luskin should have been called out on his repeated attempts to equate junk DNA with non-coding DNA. This allowed him to portray all non-coding functions as evidence against junk DNA. [Casey Luskin posts misleading quotes about junk DNA].

There are several other things that I would have done differently. I would have made it clear that 10% of the genome is functional and we don't know the function of some of that fraction. Thus, all newly discovered functional regions could still fit into the 10% and 90% of the genome is still junk. Every time Casey mentions a new function he should have been challenged to specify exactly what percentage of the genome he is referring to. (Dan tried to do this but he was too nice, and let Casey off the hook.)

The idea here is to make it clear to viewers that recent discoveries of functional regions do not affect the idea that most of our genome is junk.

I would also attempt to get Casey to admit that there's a scientific controversy over junk DNA so there are many papers defending junk DNA and criticizing the arguments of junk DNA opponents. For every quotation from a scientist who opposes junk, there's an equally significant quotation from one who supports junk. Why does Casey only quote scientists who agree with him? Is this cherry-picking? Is selectively rattling off quotations and references from people who agree with you a reasonable way to have a serious scientific debate?

I think the arguments over transcripts should begin with presenting all the scientific evidence that spurious transcripts exist - for example, random DNA sequences inserted into a cell nucleus are transcribed and spurious transcription is easily documented in well-studied organisms such as bacteria and yeast. The characteristics of spurious transcription are that the transcripts are present in very small amounts, that they are rapidly degraded, that they come from regions of the genome that are not under purifying selection, and they are cell/tissue specific. So what is the most reasonable explanation when you look at such transcripts?

Casey Luskin's attempt to avoid the best explanation (spurius transcription) is a classic example ad hoc rescue and it might have been useful to point this out to viewers.

Regulation is not new. There was serious discussion and debate over the amount of the genome devoted to regulation back in the late 1960s when the concept of junk DNA was first proposed. Casey should have been challenged to state what percentage of the genome is devoted to regulation and if he comes up with an unreasonable number he should have to give examples of many well-studied genes that have been shown to have that level of regulation. (Hint: There aren't any.) All of the detailed work on the regulation of dozens of specific human genes has shown that you don't need more than a few transcription factor binding sites to control expression. Is there any reason to suppose that the other genes require ten or a hundred times more regulatory sequences to control expression?

What is the trend line? Ever since the ENCODE publicity disaster of 2012 there has been a flood of papers defending junk DNA and the data supporting junk DNA is now stronger that it has ever been because we now know from hundreds of thousands of human genome sequences that only about 10% is under purifying selection. There have also been a lot of papers fleshing out the 10% of the genome that's functional. There have only been a handful of papers published in the past ten years that seriously attempt to present evidence that most of our genome is functional. I would have challenged Casey to come up with a single scientific publication in the past ten years claiming, with supporting data, that most of the genome is functional.

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Casey Luskin posts misleading quotes about junk DNA

On Thursday May 2, 2024, Casey Luskin and Dan Stern Cardinale debated junk DNA on the YouTube channel "The NonSequitor Show." David Klinghoffer thinks that this debate went very well for the ID side [Debate: Casey Luskin Versus Rutgers Biologist Dan Cardinale, Thursday, May 2]. I agree with Klinghoffer; Luskin did an excellent job of promoting his case because many of his statements and claims were not challenged effectively.

I'll be putting up a separate post on the debate but for now I'd like to address an article by Casey Luskin that he posted before the debate as preparation for what he was going to say. The article consists of a bunch of quotes from prominent scientists about junk DNA [“Junk DNA” from Three Perspectives: Some Key Quotes]. Here are the three perspectives, according to Luskin.

Category 1: Quotes from evolutionists claiming (or repeating the widespread belief) that non-coding DNA is “junk” and has no function.

Some of the quotes represent the actual position of junk DNA proponents but Luskin has also picked out stupid quotes from scientists who think, incorrectly, that all non-coding DNA is junk. This is deliberate as we will see below.

Category 2: Early quotes from intelligent design theorists predicting function for non-coding “junk” DNA.

Luskin builds the case for function in non-coding DNA by quoting religious scientists who "predict" that there will be functional DNA in non-coding regions of the genome. This is disingenuous at best because Luskin knows full well that from the very beginning of the scientific debate we knew about functional non-coding DNA. It was never the case that all non-coding DNA was assumed to be junk.

Category 3: Quotes from mainstream scientific sources saying that we’ve experienced a shift in our thinking that junk DNA actually has function.

Many of these quotes are from scientists announcing that some non-coding DNA has a function. They support Luskin's false claim that all non-coding DNA was thought to be junk and the discovery of functional regions of non-coding DNA has resulted in a "paradigm shift" in our view of the human genome.

Casey Luskin should not have been allowed to get away with equating junk DNA and non-coding DNA in the debate. He should have been challenged to retract that false claim at the very beginning of the debate and called out whenever he used the term "non-coding DNA" during the debate.

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