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Wednesday, March 13, 2024

Nils Walter disputes junk DNA: (7) Conservation of transcribed DNA

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 and sixth posts address specific arguments in the junk DNA debate.


Sequence conservation

If you don't know what a transcript is doing then how are you going to know whether it's a spurious transcript or one with an unknown function? One of the best ways is to check and see whether the DNA sequence is conserved. There's a powerful correlation between sequence conservation and function: as a general rule, functional sequences are conserved and non-conserved sequences can be deleted without consequence.

There might be an exception to the the conservation criterion in the case of de novo genes. They arise relatively recently so there's no history of conservation. That's why purifying selection is a better criterion. Now that we have the sequences of thousands of human genomes, we can check to see whether a given stretch of DNA is constrained by selection or whether it accumulates mutations at the rate we expect if its sequence were irrelevant junk DNA (neutral rate). The results show that less than 10% of our genome is being preserved by purifying selection. This is consistent with all the other arguments that 90% of our genome is junk and inconsistent with arguments that most of our genome is functional.

This sounds like a problem for the anti-junk crowd. Let's see how it's addressed in Nils Walter's article in BioEssays.

There are several hand-waving objections to using conservation as an indication of function and Walter uses them all plus one unique argument that we'll get to shortly. Let's deal with some of the "facts" that he discusses in his defense of function. He seems to agree that much of the genome is not conserved even though it's transcribed. In spite of this, he says,

"... the estimates of the fraction of the human genome that carries function is still being upward corrected, with the best estimate of confirmed ncRNAs now having surpassed protein-coding genes,[12] although so far only 10%–40% of these ncRNAs have been shown to have a function in, for example, cell morphology and proliferation, under at least one set of defined conditions."

This is typical of the rhetoric in his discussion of sequence conservation. He seems to be saying that there are more than 20,000 "confirmed" non-coding genes but only 10%-40% of them have been shown to have a function! That doesn't make any sense since the whole point of this debate is how to identify function.

Here's another bunch of arguments that Walter advances to demonstrate that a given sequence could be functional but not conserved. I'm going to quote the entire thing to give you a good sense of Walter's opinion.

A second limitation of a sequence-based conservation analysis of function is illustrated by recent insights from the functional probing of riboswitches. RNA structure, and hence dynamics and function, is generally established co-transcriptionally, as evident from, for example, bacterial ncRNAs including riboswitches and ribosomal RNAs, as well as the co-transcriptional alternative splicing of eukaryotic pre-mRNAs, responsible for the important, vast diversification of the human proteome across ∼200 cell types by excision of varying ncRNA introns. In the latter case, it is becoming increasingly clear that splicing regulation involves multiple layers synergistically controlled by the splicing machinery, transcription process, and chromatin structure. In the case of riboswitches, the interactions of the ncRNA with its multiple protein effectors functionally engage essentially all of its nucleotides, sequence-conserved or not, including those responsible for affecting specific distances between other functional elements. Consequently, the expression platform—equally important for the gene regulatory function as the conserved aptamer domain—tends to be far less conserved, because it interacts with the idiosyncratic gene expression machinery of the bacterium. Consequently, taking a riboswitch out of this native environment into a different cell type for synthetic biology purposes has been notoriously challenging. These examples of a holistic functioning of ncRNAs in their species-specific cellular context lay bare the limited power of pure sequence conservation in predicting all functionally relevant nucleotides.

I don't know much about riboswitches so I can't comment on that. As for alternative splicing, I assume he's suggesting that much of the DNA sequence for large introns is required for alternative splicing. That's just not correct. You can have effective alternative splicing with small introns. The only essential parts of introns sequences are the splice sites and a minimum amount of spacer.

Part of what he's getting at is the fact that you can have a functional transcript where the actual nucleotide sequence doesn't matter so it won't look conserved. That's correct. There are such sequences. For example, there seem to be some examples of enhancer RNAs, which are transcripts in the regulatory region of a gene where it's the act of transcription that's important (to maintain an open chromatin conformation, for example) and not the transcript itself. Similarly, not all intron sequences are junk because some spacer sequence in required to maintain a minimum distance between splice sites. All this is covered in Chapter 8 of my book ("Noncoding Genes and Junk RNA").

Are these examples enough to toss out the idea of sequence conservation as a proxy for function and assume that there are tens of thousands of such non-conserved genes in the human genome? I think not. The null hypothesis still holds. If you don't have any evidence of function then the transcript doesn't have a function—you may find a function at some time in the future but right now it doesn't have one. Some of the evidence for function could be sequence conservation but the absence of conservation is not an argument for function. If conservation doesn't work then you have to come up with some other evidence.

It's worth mentioning that, in the broadest sense, purifying selection isn't confined to nucleotide sequence. It can also take into account deletions and insertions. If a given region of the genome is deficient in random insertions and deletions then that's an indication of function in spite of the fact that the nucleotide sequence isn't maintained by purifying selection. The maintenance definition of function isn't restricted to sequence—it also covers bulk DNA and spacer DNA.

(This is a good time to bring up a related point. The absence of conservation (size or sequence) is not evidence of junk. Just because a given stretch of DNA isn't maintained by purifying selection does not prove that it is junk DNA. The evidence for a genome full of junk DNA comes from different sources and that evidence doesn't apply to every little bit of DNA taken individually. On the other hand, the maintenance function argument is about demonstrating whether a particular region has a function or not and it's about the proper null hypothesis when there's no evidence of function. The burden of proof is on those who claim that a transcript is functional.)

This brings us to the main point of Walter's objection to sequence conservation as an indication of function. You can see hints of it in the previous quotation where he talks about "holistic functioning of ncRNAs in their species-specific cellular context," but there's more ...

Some evolutionary biologists and philosophers have suggested that sequence conservation among genomes should be the primary, or perhaps only, criterion to identify functional genetic elements. This line of thinking is based on 50 years of success defining housekeeping and other genes (mostly coding for proteins) based on their sequence conservation. It does not, however, fully acknowledge that evolution does not actually select for sequence conservation. Instead, nature selects for the structure, dynamics and function of a gene, and its transcription and (if protein coding) translation products; as well as for the inertia of the same in pathways in which they are not involved. All that, while residing in the crowded environment of a cell far from equilibrium that is driven primarily by the relative kinetics of all possible interactions. Given the complexity and time dependence of the cellular environment and its environmental exposures, it is currently impossible to fully understand the emergent properties of life based on simple cause-and-effect reasoning.

The way I see it, his most important argument is that life is very complicated and we don't currently understand all of it's emergent properties. This means that he is looking for ways to explain the complexity that he expects to be there. The possibility that there might be several hundred thousand regulatory RNAs seems to fulfil this need so they must exist. According to Nils Walter, the fact that we haven't (yet) proven that they exist is just a temporary lull on the way to rigorous proof.

This seems to be a common theme among those scientists who share this viewpoint. We can see it in John Mattick's writings as well. It's as though the logic of having a genome full of regulatory RNA genes is so powerful that it doesn't require strong supporting evidence and can't be challenged by contradictory evidence. The argument seems somewhat mystical to me. Its proponents are making the a priori assumption that humans just have to be a lot more complicated than what "reductionist" science is indicating and all they have to do is discover what that extra layer of complexity is all about. According to this view, the idea that our genome is full of junk must be wrong because it seems to preclude the possibility that our genome could explain what it's like to be human.


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]

Sunday, March 10, 2024

The neutralist-selectionist debate in 2024

The neutral theory was first proposed by Mootoo Kimura in 1968 (Kimura, 1968). The following year, a similar idea was published in a seminal paper by Jack King and Thomas Jukes (King and Jukes, 1969). King and Jukes emphasized the importance of non-Darwinian mechanisms of evolution in order to explain protein based phylogenetic trees and the molecular clock. They made it clear that neutral alleles fixed by random genetic drift play an important part in evolution.

There appears to be considerable latitude at the molecular level for random genetic changes that have no effect upon the fitness of the organism. Selectively neutral mutations, if they occur, become passively fixed as evolutionary changes through the action of random genetic drift.

The idea of selectively neutral changes at the molecular level has not been readily accepted by many classical evolutionists, perhaps because of the pervasiveness of Darwinian thought (King and Jukes, 1969).

Thursday, March 07, 2024

Why Philosophy of Biology?

Robert Lawrence Kuhn has published a series of videos on his "Closer to Truth" site. On March 4, 2024 he posted a teaser video introducing Season 23: "Why Philosophy of Biology." The video contains short clips of his interviews with philosophers of biology (see list below).

Here's the blurb covering the introduction to the new season.

How can philosophy advance biology? How can biology influence philosophy? In this first series on Philosophy of Biology, Closer to Truth explores the challenges and implications of evolution. We ask how life on earth came to be as it is, and how humans came to be as we are. We address biologically based issues, such as sex/gender, race, cognition, culture, morality, healthcare, religion, alien life, and more. When philosophy and biology meet, sparks fly as both are enriched.

Those are all interesting questions. Some of them can only be answered by philosophers but others require major input from scientists. One of the important issues for philosophy of science seems to be the confict between the philosophy of the early 20th century, which was developed with physics as the model science, and the the success of molecular biology in the latter half of the 20th century, which didn't play by the same rules. (See the short interview with Paul Griffiths, whom I greatly admire, for a succinct explanation of this problem.)

I'm very conflicted about the role of philosphy in understanding the science of biology and even more conflicted about whether philosophers can recognize good science from bad science (Richard Dawkins, Denis Noble). I'm also puzzled by the apparent reluctance of philosophers to openly challenge their colleagues who get the science wrong. Watch the video to see if my scepticism is warranted.


Monday, March 04, 2024

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

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

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

Sunday, March 03, 2024

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

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

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

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

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

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

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

Transcripts vs junk DNA

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

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

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

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

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

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

What does transcript concentration tell us about function?

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

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

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

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

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

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

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

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


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

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

Saturday, March 02, 2024

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'

Thursday, February 29, 2024

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

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.

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

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

Any serious debate requires some definitions and the debate over junk DNA is no exception. It's important that everyone is on the same page when using specific words and phrases. Nils Walter recognizes this so he begins his paper with a section called "Starting with the basics: Defining 'function' and 'gene'."

Tuesday, February 27, 2024

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

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 second post in the series. The first one outlines the issues that led to the current paper.

Nils Walter disputes junk DNA: (1) The surprise

Walter begins his defense of function by outlining a "paradigm shift" that's illustrated in Figure 1.

FIGURE 1: Assessment of the information content of the human genome ∼20 years before (left)[110] and after (right)[111] the Human Genome Project was preliminarily completed, drawn roughly to scale.[9] This significant progress can be described per Thomas Kuhn as a “paradigm shift” flanked by extended periods of “normal science”, during which investigations are designed and results interpreted within the dominant conceptual frameworks of the sub-disciplines.[9] Others have characterized this leap in assigning newly discovered ncRNAs at least a rudimentary (elemental) biochemical activity and thus function as excessively optimistic, or Panglossian, since it partially extrapolates from the known to the unknown.[75] Adapted from Ref. [9].

Reference #9 is a paper by John Mattick promoting a "Kuhnian revolution" in molecular biology. I've already discussed that paper as an example of a paradigm shaft, which is defined as a strawman "paradigm" set up to make your work look like revolutionary [John Mattick's new paradigm shaft]. Here's the figure from the Mattick paper.

The Walter figure is another example of a paradigm shaft—not to be confused with a real paradigm shift.1 Both pie charts misrepresent the amount of functional DNA since they don't show regulatory sequences, centromeres, telomeres, origins of replication, and SARS. Together, these account for more functional DNA than the functional regions of protein-coding genes and non-coding genes. We didn't know the exact amounts in 1980 but we sure knew they existed. I cover this in Chapter 5 of my book: "The Big Picture."

The 1980 view also implies, incorrectly, that we knew nothing about the non-functional component of the genome when, in fact, we knew by then that half of our genome was composed of transposon and viral sequences that were likely to be inactive, degenerate fragments of once active elements. (John Mattick's figure is better.)

The 2020 view implies that most intron sequences are functional since introns make up more than 40% of our genome but only about 3% of the pie chart. As far as I know, there's no evidence to support that claim. About 80% of the pie chart is devoted to transcripts identified as either small ncRNAs or lncRNAs. The implication is that the discovery of these RNAs represents a paradigm shift in our understanding of the genome.

The alternative explanation is that we've known since the late 1960s that most of the human genome is transcribed and that these transcripts—most of which turned out to be introns—are junk RNA that is confined to the nucleus and rapidly degraded. Advances in technology have enabled us to detect many examples of spurious transcripts that are present transiently at low levels in certain cells. I cover this in Chaper 8 of my book: "Noncoding Genes and Junk RNA.

The whole point of Nils Walter's paper is to defend the idea that most of these transcripts are functional and the alternative explanation is wrong. He's trying to present a balanced view of the controversy so he's well aware of the fact that some of us interpret the red part of the pie chart as spurious transcripts (junk RNA). If he's wrong, and I am right, then there's no paradigm shift.

You don't get to shift the paradigm all on our own, even if John Mattick is on your side. A true paradigm shift requires that the entire community of scientists changes their perspective and that hasn't happened.

In the next few posts we'll see whether Nils Walter can make a strong case that all those lncRNAs are functional. They cover about two-thirds of the genome in the pie chart. If we assume that the average length of these long transcripts is 2000 bp then this represents one million transcripts and potentially one million non-coding genes.


1. The term "paradigm shaft" was coined by reader Diogenes in a comment on this blog from many years ago.

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]

Nils Walter disputes junk DNA: (1) The surprise

Nils Walter attempts to present the case for a functional genome by reconciling opposing viewpoints. I address his criticisms of the junk DNA position and discuss his arguments in favor of large numbers of functional non-coding RNAs.

Nils Walter is Francis S. Collins Collegiate Professor of Chemistry, Biophysics, and Biological Chemistry at the University of Michigan in Ann Arbor (Michigan, USA). He works on human RNAs and claims that, "Over 75% of our genome encodes non-protein coding RNA molecules, compared with only <2% that encodes proteins." He recently published an article explaining why he opposes junk DNA.

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

The human genome project's lasting legacies are the emerging insights into human physiology and disease, and the ascendance of biology as the dominant science of the 21st century. Sequencing revealed that >90% of the human genome is not coding for proteins, as originally thought, but rather is overwhelmingly transcribed into non-protein coding, or non-coding, RNAs (ncRNAs). This discovery initially led to the hypothesis that most genomic DNA is “junk”, a term still championed by some geneticists and evolutionary biologists. In contrast, molecular biologists and biochemists studying the vast number of transcripts produced from most of this genome “junk” often surmise that these ncRNAs have biological significance. What gives? This essay contrasts the two opposing, extant viewpoints, aiming to explain their basis, which arise from distinct reference frames of the underlying scientific disciplines. Finally, it aims to reconcile these divergent mindsets in hopes of stimulating synergy between scientific fields.

Saturday, February 17, 2024

How to end the war in Ukraine according to a Canadian Conservative "diplomat"

In my opinion, the war in Ukraine is much more complicated than most people realize. We are constantly bombarded with propaganda from all sides and it inhibits rational thinking. One of the few reliable facts is that Vladimir Putin is a very smart bad person.

Lots of people think they have the answer to ending the war in Ukraine. One of the latest pundits is Chris Alexander who has published his thoughts in the Feb. 16, 2024 edition of Canada's Globe and Mail: Ukraine is paying the price for our nonchalance toward Russia’s leadership. Alexander spent years in Canada's Foreign Service, including many years in Moscow and a stint as Canada's ambassador to Afghanistan. In 2011 he was elected to Parliament as a Conservative MP and served as Minister of Citizenship and Immigration in Stephen Harper's cabinet. His reputation as a politician was very different than his previous, mostly admirable, reputation as a diplomat. Here's a excerpt from his Wikipedia article.

Wednesday, February 14, 2024

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

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

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

Sunday, February 11, 2024

Older but wiser?

With age comes wisdom, but sometimes age comes alone.

Oscar Wilde

Like many baby boomers, I sometimes forget people's names and other important bits of information. Sometimes I can't find a word that's been in my vocabulary for decades. These lapses are often temporary but very annoying. It's a sign of age. (I am 77 years old.)

We often make fun of these incidents and consol ourselves with the knowledge that we may be old but we are much wiser than we were in our younger days. We have years and years of experience behind us and over the years we've learned a thing or two that we never understood when we were listening to the Beatles on the radio. We've lived through the Cuban Missile crisis, the war in Viet Nam, the assassination of two Kennedys and Martin Luther King, and a host of cultural changes. We've lived in several different countries and we've raised children. All of these experiences have made us wiser, or so we think.

Friday, February 09, 2024

Open and closed chromatin domains (and epigenetics)

Gene expression in eukaryotes is influenced by the state of chromatin. Tightly packed nucleosomes inhibit the binding of transcription factors and RNA polymerase so that genes in these regions are "repressed." From time to time these regions loosen up a bit allowing access to transcription complexes and subsequent transcription.

The tightly packed regions are known as closed domains and the accessible regions are open domains. Some authors add an intermediate domain called a permissive domain. This model of eukaryotic gene expression has been around for 50 years and the important mechanisms controlling the switch were worked out in the 1980s. I found a recent review that covers this issue in the context of epigenetics and the image below comes from that paper (Klemm et al., 2019).

Wednesday, February 07, 2024

Philip Ball's new book: "How Life Works"

Philip Ball has just published a new book "How Life Works." The subtitle is "A User’s Guide to the New Biology" and that should tell you all you need to know. This is going to be a book about how human genomics has changed everything.

Monday, January 29, 2024

"People also ask" about junk DNA

I'm interested in the spread of science misinformation on the internet. The misinformation about the human genome is a good example that illustrates the problem. There are many other examples but I happen to know a lot about this particular one.

Anyone trying to find out about junk DNA will find it impossible to get a correct answer by searching the internet. The correct answer is that the amount of junk DNA in the human genome is controversial: some scientists think that most of our genome is functional while others think that as much as 90% is junk. The scientific evidence strongly favors the junk side of the controvesy and that's very well explained in the Wikipedia articles on Junk DNA and Non-coding DNA.