The Function Wars Part IX: Stefan Linquist on Causal Role vs Selected Effect

How much of the human genome is functional? This a problem that will be solved by biochemists not epistemologists.

What is junk DNA? What is functional DNA? Defining your terms is a key part of any scientific controversy because you can't have a debate if you can't agree on what you are debating. We've been debating the prevalence of junk DNA for more than 50 years and much of that debate has been (deliberately?) muddled by one side or the other in order to score points. For example, how many times have you heard the ridiculous claim that all noncoding DNA was supposed to be junk DNA? And how many times have you heard that all transcripts must have a function merely because they exist?

Nils Walter disputes junk DNA: (8) Transcription factors and their binding sites

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

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

• Nils Walter disputes junk DNA: (1) The surprise
• Nils Walter disputes junk DNA: (2) The paradigm shaft
• Nils Walter disputes junk DNA: (3) Defining 'gene' and 'function'
• Nils Walter disputes junk DNA: (4) Different views of non-functional transcripts
• Nils Walter disputes junk DNA: (5) What does the number of transcripts per cell tell us about function?
• Nils Walter disputes junk DNA: (6) The C-value paradox
• Nils Walter disputes junk DNA: (7) Conservation of transcribed DNA

Nils Walter disputes junk DNA: (9) Reconciliation

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

This is the ninth and last post in the series. I'm going to discuss Walker's view on how to tone down the dispute over the amount of junk in the human genome. Here's a list of the previous posts.

• Nils Walter disputes junk DNA: (1) The surprise
• Nils Walter disputes junk DNA: (2) The paradigm shaft
• Nils Walter disputes junk DNA: (3) Defining 'gene' and 'function'
• Nils Walter disputes junk DNA: (4) Different views of non-functional transcripts
• Nils Walter disputes junk DNA: (5) What does the number of transcripts per cell tell us about function?
• Nils Walter disputes junk DNA: (6) The C-value paradox
• Nils Walter disputes junk DNA: (7) Conservation of transcribed DNA
• Nils Walter disputes junk DNA: (8) Transcription factors and their binding sites

"Conclusion: How to Reconcile Scientific Fields"

Walter concludes his paper with some thoughts on how to deal with the controversy going forward. I'm using the title that he choose. As you can see from the title, he views this as a squabble between two different scientific fields, which he usually identifies as geneticists and evolutionary biologists versus biochemists and molecular biologists. I don't agree with this distinction. I'm a biochemist and molecular biologist, not a geneticist or an evolutionary biologist, and still I think that many of his arguments are flawed.

Let's see what he has to say about reconciliation.

Science thrives from integrating diverse viewpoints—the more diverse the team, the better the science.[107] Previous attempts at reconciling the divergent assessments about the functional significance of the large number of ncRNAs transcribed from most of the human genome by pointing out that the scientific approaches of geneticists, evolutionary biologists and molecular biologists/biochemists provide complementary information[42] was met with further skepticism.[74] Perhaps a first step toward reconciliation, now that ncRNAs appear to increasingly leave the junkyard,[35] would be to substitute the needlessly categorical and derogative word RNA (or DNA) “junk” for the more agnostic and neutral term “ncRNA of unknown phenotypic function”, or “ncRNAupf”. After all, everyone seems to agree that the controversy mostly stems from divergent definitions of the term “function”,[42, 74] which each scientific field necessarily defines based on its own need for understanding the molecular and mechanistic details of a system (Figure 3). In addition, “of unknown phenotypic function” honors the null hypothesis that no function manifesting in a phenotype is currently known, but may still be discovered. It also allows for the possibility that, in the end, some transcribed ncRNAs may never be assigned a bona fide function.

First, let's take note of the fact that this is a discussion about whether a large percentage of transcripts are functional or not. It is not about the bigger picture of whether most of the genome is junk in spite of the fact that Nils Walter frames it in that manner. This becomes clear when you stop and consider the implications of Walter's claim. Let's assume that there really are 200,000 functional non-coding genes in the human genome. If we assume that each one is about 1000 bp long then this amounts to 6.5% of the genome—a value that can easily be accommodated within the 10% of the genome that's conserved and functional.

Now let's look at how he frames the actual disagreement. He says that the groups on both sides of the argument provide "complementary information." Really? One group says that if you can delete a given region of DNA with no effect on the survival of the individual or the species then it's junk and the other group says that it still could have a function as long as it's doing something like being transcribed or binding a transcription factor. Those don't look like "complimentary" opinions to me.

His first step toward reconciliation starts with "now that ncRNAs appear to increasingly leave the junkyard." That's not a very conciliatory way to start a conversation because it immediately brings up the question of how many ncRNAs we're talking about. Well-characterized non-coding genes include ribosomal RNA genes (~600), tRNA genes (~200), the collection of small non-coding genes (snRNA, snoRNA, microRNA, siRNA, PiWi RNA)(~200), several lncRNAs (<100), and genes for several specialized RNAs such as 7SL and the RNA component of RNAse P (~10). I think that there are no more than 1000 extra non-coding genes falling outside these well-known examples and that's a generous estimate. If he has evidence for large numbers that have left the junkyard then he should have presented it.

Walter goes on to propose that we should divide non-coding transcripts into two categories; those with well-characterized functions and "ncRNA of unknown function." That's ridiculous. That is not a "agnostic and neutral term." It implies that non-conserved transcripts that are present at less that one copy per cell could still have a function in spite of the fact that spurious transcription is well-documented. In fact, he basically admits this interpretation at the end of the paragraph where he says that using this description (ncRNA of unknown function) preserves the possibility that a function might be discovered in the future. He thinks this is the "null hypothesis."

The real null hypothesis is that a transcript has no function until it can be demonstrated. Notice that I use the word "transcript" to describe these RNAs instead of "ncRNA" or "ncRNA of unknown phenotypic function." I don't think we lose anything by using the word "transcript."

Walter also address the meaning of "function" by claiming that different scientific fields use different definitions as though that excuses the conflict. But that's not an accurate portrayal of the problem. All scientists, no matter what field they identify with, are interested in coming up with a way of identifying functional DNA. There are many biochemists and molecular biologists who accept the maintenance definition as the best available definition of function. As scientists, they are more than willing to entertain any reasonable scientific arguments in favor of a different definition but nobody, including Nils Walter, has come up with such arguments.

Now let's look at the final paragraph of Walter's essay.

Most bioscientists will also agree that we need to continue advancing from simply cataloging non-coding regions of the human genome toward characterizing ncRNA functions, both elementally and phenotypically, an endeavor of great challenge that requires everyone's input. Solving the enigma of human gene expression, so intricately linked to the regulatory roles of ncRNAs, holds the key to devising personalized medicines to treat most, if not all, human diseases, rendering the stakes high, and unresolved disputes counterproductive.[108] The fact that newly ascendant RNA therapeutics that directly interface with cellular RNAs seem to finally show us a path to success in this challenge[109] only makes the need for deciphering ncRNA function more urgent. Succeeding in this goal would finally fulfill the promise of the human genome project after it revealed so much non-protein coding sequence (Figure 1). As a side effect, it may make updating Wikipedia and encyclopedia entries less controversial.

I agree that it's time for scientists to start identifying those transcripts that have a true function. I'll go one step further; it's time to stop pretending that there might be hundreds of thousands of functional transcripts until you actually have some data to support such a claim.

I take issue with the phrase "solving the enigma of human gene expression." I think we already have a very good understanding of the fundamental mechanisms of gene expression in eukaryotes, including the transitions between open and closed chromatin domains. There may be a few odd cases that deviate from the norm (e.g. Xist) but that hardly qualifies as an "enigma." He then goes on to say that this "enigma" is "intricately linked to the regulatory roles of ncRNAs" but that's not a fact, it's what's in dispute and why we have to start identifying the true function (if any) of most transcripts. Oh, and by the way, sorting out which parts of the genome contain real non-coding genes may contribute to our understanding of genetic diseases in humans but it won't help solve the big problem of how much of our genome is junk because mutations in junk DNA can cause genetic diseases.

Sorting out which transcripts are functional and which ones are not will help fill in the 10% of the genome that's functional but it will have little effect on the bigger picture of a genome that's 90% junk.

We've known that less than 2% of the genome codes for proteins since the late 1960s—long before the draft sequence of the human genome was published in 2001—and we've known for just as long that lots of non-coding DNA has a function. It would be helpful if these facts were made more widely known instead of implying that they were only dscovered when the human genome was sequenced.

Once we sort out which transcripts are functional, we'll be in a much better position to describe the all the facts when we edit Wikipedia articles. Until that time, I (and others) will continue to resist the attempts by the students in Nils Walter's class to remove all references to junk DNA.

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

More stupid hype about lncRNAs

I've just posted an article about a group of scientists at UCLA who claimed to have discovered 3,000 new genes in the human genome [3,000 new genes discovered in the human genome - dark matter revealed].

They did no such thing. What they discovered was about 3,000 previously unidentified transcripts expressed at very low levels in human B cells and T cells. They declared that these low-level transcripts are lncRNAs and they assumed that the complementary DNA sequences were genes. Their actual result identifies 3,000 bits of the genome that may or may not turn out to be genes. They are PUTATIVE genes.

None of that deterred Karen Ring who blogs at The Stem Cellar: The Official Blog of CIRM, California's Stem Cell Agency. Her post on this subject [UCLA Scientists Find 3000 New Genes in “Junk DNA” of Immune Stem Cells] begins with ...

Teaching about genomes using Nessa Carey's book: Junk DNA

Nessa Carey's book about junk DNA is an embarrassment to the scientific community [Nessa Carey doesn't understand junk DNA] [The "Insulation Theory of Junk DNA"].

Today, while searching for articles on junk DNA, I came across a review of Nessa Carey's book published in The American Biology Teacher: DNA. The review was written by teacher in Colorado and she liked the book very much. Here's the opening paragraph,

The term junk DNA has been used to describe DNA that does not code for proteins or polypeptides. Recent research has made this term obsolete, and Nessa Carey elaborates on a wide spectrum of examples of ways in which DNA contributes to cell function in addition to coding for proteins. As in her earlier book, The Epigenetics Revolution (reviewed by ABT in 2013), Carey uses analogies and diagrams to relate complicated information. Although she unavoidably uses some jargon, she provides the necessary background for the nonbiologist.

The author of the review does not question or challenge the opinions of Nessa Carey and, if you think about it, that's understandable. The average biology teacher will assume that a book written by a scientist must be basically correct or it wouldn't have been published.

That's not true, as most Sandwalk readers know. You would think that biology educators should know this and exercise a little skepticism when reviewing books. Ideally, the book reviews should be written by experts who can evaluate the material in the book.

Now we have a problem. The way to correct false information about genomes and junk DNA is to teach it correctly in high school and university courses. But that means we first have to teach the teachers. Here's a case where professional teachers have been bamboozled by a bad book and that's going of make it even more difficult to correct the problem.

The last paragraph of the review shows us what influence a bad book can have,

As a biology teacher who enjoys sharing with students some details that go beyond the textbook or that challenge dogma, I enthusiastically read multiple chapters at each sitting, making note of what I cannot wait to add to class discussions. “Junk DNA” may be a misnomer, but Junk DNA is an excellent way of finding out why.

Oh dear. It's going to be hard to re-educate those students once their misconceptions have been reinforced by a teacher they respect.

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Read What Mike White Has to Say About ENCODE and Junk DNA

One of the good things to come out of this ENCODE/junk DNA fiasco is that I've discovered a number of excellent scientists who aren't afraid to speak out on behalf of science. One of them is Mike White, a systems biologist at the Center for Genome Sciences and Systems Biology, Washington Univ. School of Medicine, St. Louis (USA). He blogs at The Finch & Pea.

Mike published an impressive article on the Huffington Post a few days ago. This is a must-read for anyone interested in the controversy over junk DNA: A Genome-Sized Media Failure. Here's part of what he says ...

If you read anything that emerged from the ENCODE media blitz, you were probably told some version of the "junk DNA is debunked" story. It goes like this: When scientists realized that classical, protein-encoding genes make up less than 2% of the human genome, they simply assumed, in a fit of hubris, that the rest of our DNA was useless junk. (You might have also heard this from your high school or college teacher. Your teacher was wrong.) Along came the ENCODE consortium, which found that, far from being useless, junk DNA is packed with functionality. And so everything scientists thought they knew about the genome was wrong, wrong wrong.

The Washington Post headline read, "'Junk DNA' concept debunked by new analysis of human genome." The New York Times wrote that "The human genome is packed with at least four million gene switches that reside in bits of DNA that once were dismissed as 'junk' but that turn out to play critical roles in controlling how cells, organs and other tissues behave." Influenced by misleading press releases and statements by scientists, story after story suggested that debunking junk DNA was the main result of the ENCODE studies. These stories failed us all in three major ways: they distorted the science done before ENCODE, they obscured the real significance of the ENCODE project, and most crucially, they mislead the public on how science really works.

What you should really know about the concept of junk DNA is that, first, it was not based on what scientists didn't know, but rather on what they did know about the genome; and second, that concept has held up quite well, even in light of the ENCODE results.

Way to go, Mike!

In the past week, lot's of scientists have demonstrated that they don't know what they're talking about when they make statements about junk DNA. I don't expect any of those scientists to apologize for misleading the public. After all, their statements were born of ignorance and that same ignorance prevents them from learning the truth, even now.

However, I do expect lots of science journalists to write follow-up articles correcting the misinformation that they have propagated. That's their job.

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Catherine Shaffer Responds to My Comments About Her WIRED Article

 
Over on the WIRED website there's a discussion about the article on junk DNA [One Scientist's Junk Is a Creationist's Treasure]. In the comments section, the author Catherine Shaffer responds to my recent posting about her qualifications [see WIRED on Junk DNA]. She says,

You might be interested to learn that I contacted Larry Moran while working on this article and after reading the archives of his blog. I wanted to ask him to expand upon his assertion that junk DNA disproves intelligent design. His response was fairly brief, did not provide any references, and did not invite further discussion. It's interesting that he's now willing to write a thousand words or so about how wrong I am publicly, but was not able to engage this subject privately with me.

Catherine Shaffer sent me a brief email message where she mentioned that she had read my article on Junk DNA Disproves Intelligent Design Creationism. She wanted to know more about this argument and she wanted references to those scientists who were making this argument. Ms. Shaffer mentioned that she was working on an article about intelligent design creationism and junk DNA.

I responded by saying that the presence of junk DNA was expected according to evolution and that it was not consistent with intelligent design. I also said that, "The presence of large amounts of junk DNA in our genome is a well established fact in spite of anything you might have heard in the popular press, which includes press releases." She did not follow up on my response.

His blog post is inaccurate in a couple of ways. First, I did not make the claim, and was very careful to avoid doing so, that “most” DNA is not junk. No one knows how much is functional and how much is not, and none of my sources would even venture to speculate upon this, not even to the extent of “some” or “most.”

Her article says, "Since the early '70s, many scientists have believed that a large amount of many organisms' DNA is useless junk. But recently, genome researchers are finding that these "noncoding" genome regions are responsible for important biological functions." Technically she did not say that most DNA is not junk. She just strongly implied it.

I find it difficult to believe that Ryan Gregory would not venture to speculate on the amount of junk DNA but I'll let him address the validity of Ms. Shaffer's statement.

Moran also mistakenly attributed a statement to Steven Meyer that Meyer did not make.

I can see why someone might have "misunderstood" my reference to what Myer said so I've edited my posting to make it clear.

Judmarc and RickRadditz—Here is a link to the full text of the genome biology article on the opossum genome: Regulatory conservation of protein coding and microRNA genes in vertebrates: lessons from the opossum genome. We didn't have space to cover this in detail, but in essence what the researchers found was that upstream intergenic regions were more highly conserved in the possum compared to coding regions, but also represented a greater area of difference between possums and humans.

This appears to be a reference to the paper she was discussing in her article. It wasn't at all clear to me that this was the article she was thinking about in the first few paragraphs of her WIRED article.

Interested readers might want to read the comment by "Andrea" over on the WIRED site. She He doesn't pull any punches in demonstrating that Catherine Shaffer failed to understand what the scientific paper was saying. Why am I not surprised? (Recall that this is a science writer who prides herself on being accurate.)

So, yes, this does run counter to the received wisdom, which makes it fascinating. You are right that the discussion of junk vs. nonjunk and conserved vs. nonconserved is much more nuanced, and we really couldn't do it justice in this space. Here is another reference you might enjoy that begins to deconstruct even our idea of what conservation means: “Conservation of RET regulatory function from human to zebrafish without sequence similarity.” Science. 2006 Apr 14;312(5771):276-9. Epub 2006 Mar 23. Revjim—If you have found typographical errors in the copy, please do point them out to us. The advantage of online publication is that we do get a chance to correct these after publication.

Sounds to me like Catherine Shaffer is grasping at straws (or strawmen).

For Katharos and others—I interviewed five scientists for this article. Dr. Francis Collins, Dr. Michael Behe, Dr. Steve Meyers, Dr. T. Ryan Gregory, and Dr. Gill Bejerano. Each one is a gentleman and a credentialed expert either in biology or genetics. I am grateful to all of them for their time and kindness.

I think we all know just how "credentialed" Stephen Meyer is. He has a Ph.D. in the history and philosophy of science. Most of us are familiar with the main areas of expertise of Michael Behe and none of them appear to be science.

Making Sense of Genes by Kostas Kampourakis

Kostas Kampourakis is a specialist in science education at the University of Geneva, Geneva (Switzerland). Most of his book is an argument against genetic determinism in the style of Richard Lewontin. You should read this book if you are interested in that argument. The best way to describe the main thesis is to quote from the last chapter.

Here is the take-home message of this book: Genes were initially conceived as immaterial factors with heuristic values for research, but along the way they acquired a parallel identity as DNA segments. The two identities never converged completely, and therefore the best we can do so far is to think of genes as DNA segments that encode functional products. There are neither 'genes for' characters nor 'genes for' diseases. Genes do nothing on their own, but are important resources for our self-regulated organism. If we insist in asking what genes do, we can accept that they are implicated in the development of characters and disease, and that they account for variation in characters in particular populations. Beyond that, we should remember that genes are part of an interactive genome that we have just begun to understand, the study of which has various limitations. Genes are not our essences, they do not determine who we are, and they are not the explanation of who we are and what we do. Therefore we are not the prisoners of any genetic fate. This is what the present book has aimed to explain.

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

I'm discussing a recent paper published by Nils Walter (Walter, 2024). He is trying to explain the conflict between proponents of junk DNA and their opponents. His main focus is building a case for large numbers of non-coding genes.

This is the third post in the series. The first one outlines the issues that led to the current paper and the second one describes Walter's view of a paradigm shift. The third post describes the differing views on how to define key terms such as 'gene' and 'function.' In this post I'll describe the heart of the dispute according to Nils Walter.

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

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

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

What's in your genome?: 2021

This is an updated version of what's in your genome based on the latest data. The simple version is ...

about 90% of your genome is junk

Only 10.7% of the human genome is conserved

The Zoonomia project aligned the genome sequences of 240 mammalian species and determined that only 10.7% of the human genome is conserved. This is consistent with the idea that about 90% of our genome is junk.

The April 28, 2023 issue of science contains eleven papers reporting the results of a massive study comparing the genomes of 240 mammalian species. The issue also contains a couple of "Perspectives" that comment on the work.

Pwned by lawyers (not)

A few days ago I mentioned a post by Barry Arrington where he said, "You Should Know the Basics of a Theory Before You Attack It. I pointed out the irony in my post.

Barry Arringotn took exception and challenged me in: Larry Moran's Irony Meter.

OK, Larry. I assume you mean to say that I do not understand the basics of Darwinism. I challenge you, therefore, to demonstrate your claim.

This was the kind of challenge that's like shooting fish in a barrel but I thought I'd do it anyway in case it could serve as a teaching moment. Boy, was I wrong! Turns out that ID proponents are unteachable.

I decided to concentrate on Arrington's published statements about junk DNA where he said ...

Will the IDiots Make the Same Mistake with RNA that They Made with Junk DNA?

 
Robert Crowther (whoever that is) posted a similar question on the Intelligent Design Creationis blog of the Discovery Institute. His question was Will Darwinists Make the Same Mistake with RNA that They Made in Ignoring So-Called "Junk" DNA?.

One interesting thing that leapt out at me when reading this was the fact that, while many scientists now realize that it was a mistake to jump to the conclusion that there were massive amounts of "junk" in DNA (because they were trying to fit the research into a Darwinian model), they are on the verge of committing the same exact mistake all over again, this time with RNA.

In order to understand such a bizarre question you have to put yourself in the shoes of an IDiot. They firmly believe that the concept of junk DNA has been overturned by recent scientific results. According to them, the predictions of Intelligent Design Creationism have been vindicated and all of the junk DNA has a function.

Of course this isn't true but, unfortunately, there are some scientists whose level of intelligence is not much above that of the typical IDiot [Junk DNA in New Scientist] [The Role of Ultraconserved Non-Coding Elements in Mammalian Genomes].

Now the IDiots have turned their attention to RNA. They fell hook line and sinker for the hype about functional sequences in junk DNA and they're falling just as easily for the hype about new RNAs. They believe all those silly papers that attribute function to every concevable RNA molecule that has ever been predicted or detected in some assay.

The IDiots were wrong about junk DNA and they're wrong about RNA. The answer to my question is "yes," the IDiots will make the same mistake. You can practically count on it. The answer to Crowther's question is "no." Most (but not all) scientists did not fall for the spin on junk DNA and they realize that the vast majority of our genome is junk. In the long run, they will not fall for the claim that most of the junk DNA is functional because it encodes essential RNA molecules.

What's In Your Genome? - The Pie Chart

Here's my latest compilation of the composition of the human genome. It's depicted in the form of a pie chart.¹ [UPDATED: March 29, 2018]

What is the dominant view of junk DNA?

I think that about 90% of our genome is junk and I know lots of other scientists who feel the same way. I'm pretty sure that this view is not shared by the majority of scientists but I don't know whether they are convinced that most of our genome is functional or whether they just think the question is unanswerable at the present time. I suspect that the latter view is more common but I'd like to hear your opinion.

Evolution and Junk DNA in Chicago

I just signed up for the SMBE Conference in Chicago in July. There's lots of cool talks about evolution but, in the end, I decided I just couldn't miss the session on "Where did 'junk' go?" with Wojciech Makalowski as organizer. Here's the blurb ...

Late Susumu Ohno once said "So much junk DNA in our genome" and the phrase junk DNA was born. For a long time mainstream scientists avoided these parts of the genome. However, over the years the picture slowly started to appear suggesting that the junk DNA hides a genomic treasure. With the completion of the current ENCODE project, junk DNA effectively disappeared because there's no longer useless DNA in the genome. This symposium will discuss the current understanding of these not-so-long-ago obscure areas of the genome, with special attention to transposable elements' activities and their evolutionary consequences. The integral part of the symposium will be general discussion of Ohno’s idea and its place in today's biology.

I'm familiar with Makalowski's way of thinking—it resembles the opinions of many Intelligent Design Creationists even though Makalowski is not a creationist [see Junk DNA: Scientific American Gets It Wrong (again)]. Back in 2007 he said,

Although very catchy, the term "junk DNA" repelled mainstream researchers from studying noncoding genetic material for many years. After all, who would like to dig through genomic garbage?

We know who's been invited to talk.

1. Josefa Gonzalez (Institut de Biologia Evolutiva, Barcelona, Spain)
   "Adaptation is the key concept in Evolutionary Biology. Understanding adaptation has important scientific and social implications since adaptation underlies processes such as the ability of species to survive in changing environments, resistance to antibiotics and cancer chemotherapies and host-pathogen interactions, among others.
   However, adaptation is to date a very poorly understood process largely because the current approaches to the study of adaptation are often exclusively based on a priori candidate genes or on searching for signals of selection at the DNA level giving us an incomplete and biased picture of the adaptive process.
   
   In our lab we aimed at understanding the molecular process of adaptation and its functional consequences. Towards this end, we study recent transposable element (TE)-induced adaptations in Drosophila melanogaster."
2. Valer Gotea (National Human Genome Institute, Bethesda, USA)
   "... it is not surprising that TEs [transposable elements] have a significant influence on the genome organization and evolution. What once was called junk now is considered a treasure. Although much progress has been achieved in understanding of a role that TEs play in a host genome, we are still far from a full understanding of the delicate evolutionary interplay between a host genome and the invaders"
3. Dan Graur (University of Houston, Houston, USA)
   "This absurd conclusion was reached through various means, chiefly (1) by employing the seldom used “causal role” definition of biological function and then applying it inconsistently to different biochemical properties, (2) by committing a logical fallacy known as “affirming the consequent,” (3) by failing to appreciate the crucial difference between “junk DNA” and “garbage DNA,” (4) by using analytical methods that yield biased errors and inflate estimates of functionality, (5) by favoring statistical sensitivity over specificity, and (6) by emphasizing statistical significance rather than the magnitude of the effect."
4. Dixie Mager (University of British Columbia, Canada)
   "The fact that transposable elements (TEs) can influence host gene expression was first recognized more than 50 years ago. However, since that time, TEs have been widely regarded as harmful genetic parasites-selfish elements that are rarely co-opted by the genome to serve a beneficial role. Here, we survey recent findings that relate to TE impact on host genes and remind the reader that TEs, in contrast to other noncoding parts of the genome, are uniquely suited to gene regulatory functions. We review recent studies that demonstrate the role of TEs in establishing and rewiring gene regulatory networks and discuss the overall ubiquity of exaptation. We suggest that although individuals within a population can be harmed by the deleterious effects of new TE insertions, the presence of TE sequences in a genome is of overall benefit to the population."
5. Masumi Nozawa (National Genetic Institute, Mishima, Japan)
   (I don't know anything about his work. Can anybody help?

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University press releases are a major source of science misinformation

Here's an example of a press release that distorts science by promoting incorrect information that is not found in the actual publication.

The problems with press releases are well-known but nobody is doing anything about it. I really like the discussion in Stuart Ritchie's recent (2020) book where he begins with the famous "arsenic affair" in 2010. Sandwalk readers will recall that this started with a press conference by NASA announcing that arsenic replaces phosphorus in the DNA of some bacteria. The announcement was treated with contempt by the blogosphere and eventually the claim was discproved by Rosie Redfield who showed that the experiment was flawed [The Arsenic Affair: No Arsenic in DNA!].

This was a case where the science was wrong and NASA should have known before it called a press conference. Ritchie goes on to document many cases where press releases have distorted the science in the actual publication. He doesn't mention the most egregious example, the ENCODE publicity campaign that successfully convinced most scientists that junk DNA was dead [The 10th anniversary of the ENCODE publicity campaign fiasco].

I like what he says about "churnalism" ...

In an age of 'churnalism', where time-pressed journalists often simply repeat the content of press releases in their articles (science news reports are often worded vitrually identically to a press release), scientists have a great deal of power—and a great deal of responsibility. The constraints of peer review, lax as they might be, aren't present at all when engaging with the media, and scientists' biases about the importance of their results can emerge unchecked. Frustratingly, once the hype bubble has been inflated by a press release, it's difficult to burst.

Press releases of all sorts are failing us but university press releases are the most disappointing because we expect universities to be credible sources of information. It's obvious that scientists have to accept the blame for deliberately distorting their findings but surely the information offices at universities are also at fault? I once suggested that every press release has to include a statement, signed by the scientists, saying that the press release accurately reports the results and conclusions that are in the published article and does not contain any additional information or speculation that has not passed peer review.

Let's look at a recent example where the scientists would not have been able to truthfully sign such a statement.

A group of scientists based largely at The University of Sheffield in Sheffield (UK) recently published a paper in Nature on DNA damage in the human genome. They noted that such damage occurs preferentially at promoters and enhancers and is associated with demethylation and transcription activation. They presented evidence that the genome can be partially protected by a protein called "NuMA." I'll show you the abstract below but for now that's all you need to know.

The University of Sheffield decided to promote itself by issuing a press release: Breaks in ‘junk’ DNA give scientists new insight into neurological disorders. This title is a bit of a surprise since the paper only talks about breaks in enhancers and promoters and the word "junk" doesn't appear anywhere in the published report in Nature.

The first paragraph of the press release isn' very helpful.

‘Junk’ DNA could unlock new treatments for neurological disorders as scientists discover how its breaks and repairs affect our protection against neurological disease.

What could this mean? Surely they don't mean to imply that enhancers and promoters are "junk DNA"? That would be really, really, stupid. The rest of the press release should explain what they mean.

The groundbreaking research from the University of Sheffield’s Neuroscience Institute and Healthy Lifespan Institute gives important new insights into so-called junk DNA—or DNA previously thought to be non-essential to the coding of our genome—and how it impacts on neurological disorders such as Motor Neurone Disease (MND) and Alzheimer’s.

Until now, the body’s repair of junk DNA, which can make up 98 per cent of DNA, has been largely overlooked by scientists, but the new study published in Nature found it is much more vulnerable to breaks from oxidative genomic damage than previously thought. This has vital implications on the development of neurological disorders.

Oops! Apparently, they really are that stupid. The scientists who did this work seem to think that 98% of our genome is junk and that includes all the regulatory sequences. It seems like they are completely unaware of decades of work on discovering the function of these regulatory sequences. According The University of Sheffield, these regulatory sequences have been "largely overlooked by scientists." That will come as a big surprise to many of my colleagues who worked on gene regulation in the 1980s and in all the decades since then. It will probably also be a surprise to biochemistry and molecular biology undergraduates at Sheffield—at least I hope it will be a surprise.

Professor Sherif El-Khamisy, Chair in Molecular Medicine at the University of Sheffield, Co-founder and Deputy Director of the Healthy Lifespan Institute, said: “Until now the repair of what people thought is junk DNA has been mostly overlooked, but our study has shown it may have vital implications on the onset and progression of neurological disease."

I wonder if Professor Sherif El-Khamisy can name a single credible scientist who thinks that regulatory sequences are junk DNA?

There's no excuse for propagating this kind of misinformation about junk DNA. It's completely unnecessary and serves only to discredit the university and its scientists.

Ray, S., Abugable, A.A., Parker, J., Liversidge, K., Palminha, N.M., Liao, C., Acosta-Martin, A.E., Souza, C.D.S., Jurga, M., Sudbery, I. and El-Khamisy, S.F. (2022) A mechanism for oxidative damage repair at gene regulatory elements. Nature, 609:1038-1047. doi:[doi: 10.1038/s41586-022-05217-8]

Oxidative genome damage is an unavoidable consequence of cellular metabolism. It arises at gene regulatory elements by epigenetic demethylation during transcriptional activation1,2. Here we show that promoters are protected from oxidative damage via a process mediated by the nuclear mitotic apparatus protein NuMA (also known as NUMA1). NuMA exhibits genomic occupancy approximately 100 bp around transcription start sites. It binds the initiating form of RNA polymerase II, pause-release factors and single-strand break repair (SSBR) components such as TDP1. The binding is increased on chromatin following oxidative damage, and TDP1 enrichment at damaged chromatin is facilitated by NuMA. Depletion of NuMA increases oxidative damage at promoters. NuMA promotes transcription by limiting the polyADP-ribosylation of RNA polymerase II, increasing its availability and release from pausing at promoters. Metabolic labelling of nascent RNA identifies genes that depend on NuMA for transcription including immediate–early response genes. Complementation of NuMA-deficient cells with a mutant that mediates binding to SSBR, or a mitotic separation-of-function mutant, restores SSBR defects. These findings underscore the importance of oxidative DNA damage repair at gene regulatory elements and describe a process that fulfils this function.

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ENCODE and their current definition of "function"

ENCODE has mostly abandoned it's definition of function based on biochemical activity and replaced it with "candidate" function or "likely" function, but the message isn't getting out.

Back in 2012, the ENCODE Consortium announced that 80% of the human genome was functional and junk DNA was dead [What did the ENCODE Consortium say in 2012?]. This claim was widely disputed, causing the ENCODE Consortium leaders to back down in 2014 and restate their goal (Kellis et al. 2014). The new goal is merely to map all the potential functional elements.

... the Encyclopedia of DNA Elements Project [ENCODE] was launched to contribute maps of RNA transcripts, transcriptional regulator binding sites, and chromatin states in many cell types.

The new goal was repeated when the ENCODE III results were published in 2020, although you had to read carefully to recognize that they were no longer claiming to identify functional elements in the genome and they were raising no objections to junk DNA [ENCODE 3: A lesson in obfuscation and opaqueness].

Non-Darwinian Evolution in 1969: The Case for Junk DNA

I've been having a discussion with Elizabeth Liddle in the comments to: Barry Arrington, Junk DNA, and Why We Call Them Idiots . I think it's important to understand why scientists first started thinking that most of our genome is junk. It's important to understand that these scientists were not Darwinists and their predictions were not based on an understanding of natural selection.

Let's look at a famous paper by Jack Lester King and Thomas Hughes Jukes.¹ The title of the paper is "Non-Darwinian Evolution" and it was published 44 years ago in the May 16, 1969 issue of Science [read it at: Science 164:788-798].

The subtitle of the paper is "Most evolutionary change in proteins may be due to neutral mutations and genetic drift" but that's not what I want to talk about. This paper is among the first to predict the presence of large amounts of junk DNA in our genome. King and Jukes didn't call it "junk"—that term was introduced by Susumu Ohno in 1972—but that doesn't matter. When King and Jukes talk about "superfluous DNA" they mean "junk."

Here's the relevant part of the paper ...

The 10th anniversary of the ENCODE publicity campaign fiasco

On Sept. 5, 2012 ENCODE researchers, in collaboration with the science journal Nature, launched a massive publicity campaign to convince the world that junk DNA was dead. We are still dealing with the fallout from that disaster.

The Encyclopedia of DNA Elements (ENCODE) was originally set up to discover all of the functional elements in the human genome. They carried out a massive number of experiments involving a huge group of researchers from many different countries. The results of this work were published in a series of papers in the September 6th, 2012 issue of Nature. (The papers appeared on Sept. 5th.)