New Scientist has produced a special issue on the best ideas of the 21st century. Here's the complete list.
- Microbiome: The hidden microscopic ecosystem shaping our health
- Neurodiversity: The revolutionary realisation that there's no such thing as a "typical" brain
- Our new family tree: The unexpectedly epic saga of our species Homo sapiens and its predecessors
- Our solar system is weird: The revelations that the cosmos is mostly very different from our strange little corner of it
- Transformer architecture: The common foundation of today's AI giants
- Net zero:The surprising moment that changed the whole planet’s approach to climate change
- What should we eat?: Time and time again, scientists have found one diet beats all others when it comes to our health
- Smartphones: A computer in every person’s pocket – why the pros outweigh the cons
- Transient astronomy: Watching the universe’s biggest dramas in real time
- Epigenetics: How your surprisingly simple genome builds an extraordinarily complex you
- Embracing quatnum weirdness: Albert Einstein doubted quantum theory – but accepting its strangeness has led to great things
- Gigafactories: The unprecedented step towards electrifying everything
- Climae attribution studies: A groundbreaking technique that brings the devastating consequences of climate change home
- Brain meworks: The eureka discovery that revealed the origins of our most complex thought processes
- CRISPR: We finally have the power to edit our own genetic code
- Click chemistry: A powerful new technique for making the stuff of life
- Wikipedia: The world’s most surprising and essential hub of knowledge
- Landscape of fear: How predators drastically shape ecosystems – in ways we’d never predicted
- 1.5°C: The unlikely target that transformed global climate ambitions
- End-to-end encryption: A wall that keeps our digital secrets safe
- Managing HIV: The game-changing preventative drugs that have benefitted millions
To me, this list says a lot about the poor quality of today's science writers.1 I'll pick just one as an example.
The hidden power of epigenetics: Best ideas of the century
Following the surprising discovery that our genetic blueprint is much simpler than expected, we’ve rapidly learned that we have epigenetics to thank for our extraordinary complexity
by Colin Barras
The article begins with the common false history of the number of genes in the human genome.
... those ignorant of history are not condemned to repeat it; they are merely destined to be confused.At the dawn of the millennium, the number of genes in our genome was still up for discussion. When we finally got our first official estimate, the number was so far below expectations that it helped turbocharge a movement to rethink the evolutionary process.
In 2001, the Human Genome Project announced we have no more than 40,000 protein-coding genes – a figure that has since been revised down to about 20,000. We needed other mechanisms to explain the complexity of our biology and evolution. It was epigenetics’ time to shine.
Epigenetics is a catch-all term to describe how a wide variety of molecules interact with DNA or RNA to influence the activity of genes without changing the underlying genetic code. Two cells with identical genomes but different epigenetic markers can look and behave very differently.
Stephen Jay Gould
Ontogeny and Phylogeny (1977)
Sandwalk readers will be familiar with this story. When the human genome sequence was published there were lots of scientists and science writers who had not kept up with the scientific literature on the number of genes in the human genome. The knowledgeable experts had been predicting about 30,000 genes based on evidence dating back to the late 1960s. It was no surprise to them that their predictions turned out to be correct. [Hisorical estimates of the number of genes]
The result was a surprise to scientists and science writers who were expecting many more genes based largely on their ignorance of the scientific literature. They assumed that humans must have lots of genes because humans are so complex.
Under normal circumstances, when a scientific result doesn't conform to your expectations it's time to reevaluate your assumptions. That didn't happen. These surprised scientists and science writers didn't delve into the literature to find out why the knowledgeable experts were correct or why their assumptions might have been flawed. Instead, they tried to rescue their beliefs by coming up with multiple explanations for why we could still be the most complex species even if we had the same number of genes as "lower" species.
The explanations included alternative splicing, non-coding genes, complex regulation, transposons, pseudogenes, and epigenetics. All of these excuses explanations are designed to account for the missing compexity that's supposed to distinguish humans from all other species.
This is the Deflated Ego Problem and their form of argument is a fallacy known as Ad Hoc Rescue The fallacy is described by Chris DiCarlo in his book on critical thinking.2
Ad Hoc Rescue
The term ad hoc is Latin and literally means “for this purpose.” It involves the addition of more premises in an attempt to save a particular belief or position. By itself, adding more propositions is not fallacious. It becomes fallacious, however, when one’s new propositions do not possess convincing evidence but merely reflect a person’s biased ties to the cherished belief of position.
Epigenetics is a fancy word for regulation of gene expression. It is not a 21st century idea. It's been around since the 1960s (>60 years). The most common form of regulation is at the level of transcription initiation and that's controlled by the binding of transcription factors near the transcription start site. These transcription factors may be activators or repressors.
This basic level of control is augmented in eukaryotes by changes in chromatin structure. There are basically two forms of chromatin: a tightly packed form of nucleosomes called a "closed domain" and a more open form called an "open domain" [Open and closed chromatin domains (and epigenetics)]. The shift from one form to the other is aided by the methylation (closed domain) or demethylation (open domain) of DNA and by modifications of the histone molecules in the nucleosomes.
These changes (demethylation and histone modification) are triggered by the binding of transcription factors that lead to activation of a nearby gene. It's important to note that changes in methylation and histone modification are almost always consequences of transcription factor binding and not causes of regulation. It is the transcription factors that recognize specific DNA sequences leading to activation of certain genes.3
The thing that nature figured out—it’s kind of amazing, actually—is that once you have all the reading machinery, it’s just a question of recruiting it to the right place. And to do that we have evolved these very simple little factors that get together and attract the RNA polymerase to the gene.
This is a quotation from Kat Arney's interview with Mark Ptashne in her book Herding Hemingway's Cats (p.58). Ptashne is referring to his "recruitment model" (Ptashne and Gann, 1997; Ptashne, 2013) and what he means is that the E. coli and bacteriophage model is probably (mostly) true of eukaryotes as well. Support for the recruitment model is a way of fighting back against the hype of chromatin changes and "epigenetics" (whatever that is) and against the idea that post-transcriptional mechanisms of regulation such as alternative splicing, RNA degradation, and translational control by regulatory RNAs play a significant role in controlling the concentration of proteins in a eukaryotic cell.
- Protein concentrations in E. coli are mostly controlled at the level of transcription initiation
- New Scientist promotes misinformation about evolution
- What do believers in epigenetics think about junk DNA?
- What the heck is epigenetics?
- Core Misconcept: Epigenetics
- Calico Cats
1. I'm surprised that mRNA vaccines didn't make the list.
2. DiCarlo, C. (2011) How to Become a Really Good Pain in the Ass: A Critical Thinker's Guide to Asking the Right Questions, Prometheus Books, Amhurst, New York, USA (p. 128)
3. See the link to calico cats as an exception that proves the rule.
p>Ptashne, M. and Gann, A. (1997) Transcriptional activation by recruitment. Nature 386:569-577. [doi: 10.1038/386569a0]Ptashne, M. (2013) Epigenetics: core misconcept. Proceedings of the National Academy of Sciences (USA) 110:7101-7103. [doi: 10.1073/pnas.1305399110]
25 comments :
I agree with you on the point that DNA methylation and histones tagging like ( histones Acetylation, Methylation, Phosphorylation, Ubiquitination, Sumoylation, ADP-ribosylation, Citrullination (Deimination), Glycosylation, Crotonylation, Propionylation, Butyrylation, Succinylation, Malonylation, Lactylation)
And combination of all of them , are ultimately recruited by enzymes which are themselves recruited by transcription factors.
But you missed the point that combinatorial arrangements of These chemical Tags code for enormous amount of information, famously known as histones Code.
That's another great layer of information processing system truly beyond primary DNA sequence
@Mehrshad: You would have to convince me that there's a correlation between the histone code and different effects on gene expression.
Then you would have to convince me that the different amounts of histone modifications are independent of any transcription factors that recognize and bind to particular regulatory sites. It's hard for me to imagine that there could be a histone code that's independent of the DNA regulatory sequence. Do you know of any mechanism that would make that work?
David Allis (1951 - 2023) and the "histone code"
{You would have to convince me that there's a correlation between the histone code and different effects on gene expression.}
Of course that there's a correlation!!. Every High school biology student knows that histone methylation are usually associated with heterochromatin and Acitilation with Eukromatin Formation respectively.
{It's hard for me to imagine that there could be a histone code that's of them independent of the DNA regulatory sequence.}
I didn't say it's independent, I've Just Said histone Codes make the basement for another Higher layer of information processing.
Two examples that I'm aware of are neuclusomes remodeling enzymes (which are Giant molecular machines dedicated to histone sliding, eviction, variant exchange).... The decision of where to bind and how to act and so many other things are determined by epigenetic Code.
Another example is the role of histone code in DNA repair. The desicions of which pathway to choose for which type of DNA damage is determined by epigenetic Code again .
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There has been an exhibition on 21st centyury science on during the 1962 World's fair in Seattle. You will find some information on its biology part at the Panda's Tumb. https://pandasthumb.org/archives/2022/01/21st-century-left-handed-DNA.html
There is still the claim that humans are the most complex organisms, and this claim is seldom questioned. I think the only aspect of that which MAY be true enough is our prefrontal cortex, which is a thin layer of gray matter in the forebrain that you can cover with your hand. Which makes it "complex", apparently , is neural density and connectivity. I don't know how this develops, but it isn't a given that we need extra information in our genome to build it.
@Mehrshad: Point taken. I shouldn't have used the word "correlation" when I was actually talking about cause and effect. What I meant to say is that I don't believe that modifications to histones (histone code) are, by themselves, responsible for regulating gene expression.
I think they are consequences or secondary effects following the binding of transcription factors that recognize specific DNA sequences.
Hmmm the choice still feels a bit contrived, why choose the prefrontal cortex or the brain in particular? Birds, for instance, have lungs that are way more complex and impressive than any mammalian lung... There is no single standard against which to judge all living beings as if they had to rest on a complexity ladder imho.
Larry wrote:
"Epigenetics is a fancy word for regulation of gene expression."
"epigenetics" (whatever that is).
I found the following definition of epigenetic regulation:
"The *inheritance* of gene expression patterns, in the absence of both mutation and initiating signal, is called epigenetic regulation." (my emphasis)
James Watson et al. (2008) Molecular Biology of the Gene, page 626.
As I understand it, it explains how cells with the same DNA can differentiate into various tissues (in multicellular organisms).
Vox Day's critique of the modern synthesis may be the first substantive counterargument I've heard in quite some time. I've always intuitively felt that something about neutral theory seemed "off" but couldn't quite put my finger on it.
Is there a distinction being made here (or by New Scientist) between "epigenetics" as differences between cells in one organism during its development, and "epigenetic" differences between gametes?
Didn't "epigenetics" used to refer to physical interactions (cell-cell contact and interaction, for example) during development?
gert korthof said, "As I understand it, [epigenetics] explains how cells with the same DNA can differentiate into various tissues (in multicellular organisms)."
Sean B, Carroll (the biologist) wrote a whole book ("Endless Forms Most Beautiful") explaining evo-devo. It's all about transcription factors. He never mentioned the word "epigenetics."
@Anonymous: If you're a fan of Vox Day then this isn't the place for you. You should check out the pseudoscience and religious blogs.
Larry, I quoted the definition of 'epigenetic regulation' from Watson et al (2008) Molecular Biology of the Gene, and you reply with: epigenetics is not present in Endless Forms Most Beautiful, while completely ignoring the Watson textbook.
Are you serious? Dislike of a word is not a valid argument against it.
Not a huge Vox Day fan but I was hoping there was still some fight in the old lions. In the old days you fought well against Dembski and Luskin who merely operated at the periphery of the realm. But Vox Day is striking pretty effectively at the very heart of evolutionary biology, and he's brought mercenaries with him. Dennis McCarthy mounted what looked at first to be a valiant defense, but now appears to be just embarrassing himself as it becomes clear he didn't even read the book he attempted to refute.
I won't bother you old lions any more.
@gert Korthof: I was responding to your comment that epigenetics explains development and differentiation by pointing out that leading researchers are able to explain the fundamentals of evo-devo without mentioning epigenetics.
I don't doubt that you can find all kinds of definitions of epigenetics in various textbooks and scientific publications. That's not the question. The question is whether those definitions hold up to close scrutiny and whether the term "epigenetics" actually means anything significant.
For example, the definition you quote from Watson emphasizes "inheritance of gene expression patterns." Watson et al. then go on to describe an example using lysogeny in bacteriophage lambda. In the lysogenic state, most of the lambda genes are repressed by lambda repressor and this state is inherited every time the cell divides.
They also describe the inheritance of lac gene expression in E. coli and GAL gene expression in yeast.
It's well-known that methylation of DNA is heritable - that comes from work on restriction-modification in the 1970s. Watson et al also describe that phenomenon.
They show one example of imprinting where the binding of a transcription factor depends on the methylation state in the same way that the binding of a restriction protein depends on the state of methylation.
The sentence you quoted comes at the end of a longer paragraph. (Quoting from the 2004 edition.)
"Patterns of gene expression must sometimes be inherited. A signal released by one cell during development causes neighboring cells to switch on certain genes. Those genes may have to remain on in those cells for many generations, even if the signal that induced them is present only fleetingly. The inheritance of gene expression patterns, in the absence of either mutation or the initiating event is called epigenetic regulation. The imprinting example we discussed above reveals one way the expression of a gene can be regulated epigenetically."
It's clear from all the Watson et al. examples that what they are referring to is the inheritance and regulation of transcription factor binding that activates or represses gene expression. This is a trivial definition of epigenetics that does not constitute one of the best ideas of the 21st century.
“When I use a word,” Humpty Dumpty said, in rather a scornful tone, “it means just what I choose it to mean—neither more nor less.” “The question is,” said Alice, “whether you can make words mean so many different things.” “The question is,” said Humpty Dumpty, “which is to be master—that’s all.” Lewis Carroll (Charles L. Dodgson) Through the Looking-Glass (1872)
Check out this post for a serious discussion of how to define epigenetics.
What the heck is epigenetics?
Do you suppose that "Anonymous" might be Vox Day trying to hype his book?
Well, this "anonymous" seems to be shocked that anyone would respond to the book without reading it, and doesn't offer any free copies. Since the evidence indicates that the book's argument consists of PRATTs (Points Refuted A Thousand Times), the hyping is unlikely to work.
Larry, thanks for your detailed reply and the link to your 2017 blog post.
Because some scientists make false claims about epigenetic inheritance or promote it as one of "the best ideas of the 21st century" is no valid reason to remove epigenetic inheritance from the scientific vocabulary.
In your 2017 blog, you did agree with the Deans and Maggert chromosome-bound definition of epigenetic inheritance. So, you demonstrate that it is meaningful to discuss and evaluate the definition of words (against Lewis Carroll).
Epigenetic inheritance is essential for cell differentiation and maintaining a stable cell identity across cell divisions. So, it is a crucial part of the invention of multicellularity in evolution. I do agree that 'Endless Forms' is an excellent book, but the description of Sean B Carroll of evo-devo is incomplete without epigenetic inheritance (because he is describing multicellular creatures).
Some forms of epigenetic inheritance is necessary for even the possibility of cellular life. If the daughter cell doesn't inherit already-made ribosomes then it has no way to translate genes into new proteins. It must inherit some of the products of already expressed genes, as it is these products that go on to express other genes in turn.
This demonstrates that non-genetic inheritance must necessarily go back to the very origin of cells, and it leads to the thought-provoking idea that there could be forms of information transfer predating genetics entirely (such as compositional information transfer or others).
Mikkel Rumraket Rasmussen: I fully agree that "It must inherit some of the products of already expressed genes." It could be applied to the fertilized egg cell: it must contain all the necessary tRNAs, etc. etc. too. Otherwise, not a single gene can be transcribed, translated. In other words: the fertilized egg has a boot problem.
The question is whether epigenetic inheritance, which is important in individual development and in starting up the zygote, is of any importance in long-term inheritance in populations, and thus would be a factor in evolution. And I think the answer is "no".
Yes but that is exactly the point that Larry was trying to make. Where ribosomes bind, which promoters get methylated and so on, ultimately depends on the DNA sequence, so epigenetics is not the spectacular breakthrough concept/mechanism it's hyped to be. The expression patterns are pre-existing. It's like the glue that one uses to paint a jigsaw puzzle with. The number and colours of the pieces don't change because you use more or less glue here or there!
Anonymous said "..which promoters get methylated and so on, ultimately depends on the DNA sequence..."
but the dna sequence of all cells in our body is the same, isn't it? Yet, there are hundreds of different cell types in our body. How is that possible if methylation ultimately depends on the DNA sequence"?
For the people who are less impressed with epigenetics (much of which has merit), are you more impressed by microRNA and its role in post-transcriptional gene regulation?
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