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Showing posts sorted by relevance for query central dogma. Sort by date Show all posts
Showing posts sorted by relevance for query central dogma. Sort by date Show all posts

Thursday, June 27, 2013

Better Biochemistry

This is a "Theme" post where I collect all previous posts on teaching biochemistry and molecular biology.

March 22, 2015
On the handedness of DNA

March 5, 2015
Don't misuse the word "homology"

January 28, 2015
Vision and Change

January 28, 2015
Evidence-based teaching

January 15, 2015
The Nature of Science (NOS)

January 11, 2015
Why can't we teach properly?

January 8, 2015
Evolutionary biochemistry and the importance of random genetic drift

January 3, 2015
Thinking critically about the Central Dogma of Molecular Biology

December 9, 2014
On the meaning of pH optima for enzyme activity

December 9, 2014
On the specificity of enzymes

December 4, 2014
How to revolutionize education

October 20, 2014
How not to teach biochemistry

October 3, 2014
Metabolism first and the origin of life

September 11, 2014
The mystery of Maud Menten

August 8, 2014
Historical contingency and the evolution of the glucocorticoid receptor

July 28, 2014
Finding the "perfect" enzyme

Jun 2, 2014
"Flipping the classroom": what does that mean?

April 25, 2014
ASBMB Core Concepts in Biochemistry and Molecular Biology: Molecular Structure and Function

April 24, 2014
ASBMB Core Concepts in Biochemistry and Molecular Biology: Biological Information

March 21, 2014
ASBMB Core Concepts in Biochemistry and Molecular Biology: Homeostasis

March 5, 2014
The crystal structure of E. coli RNA polymearse σ70 holoenzyme

January 10, 2014
How not to teach biochemistry at memorize.com

December 9, 2013
Monday's Molecule #226

December 6, 2013
Die, selfish gene, die!

December 6, 2013
Do you understand this Nature paper on transcription factor binding in different mouse strains?

December 2, 2013
Monday's Molecule #225

November 12, 2013
David Evans Says, "Teach What the Vast Majority of Scientists Affirm as Settled Science"

November 5, 2013
Stop Using the Term "Noncoding DNA:" It Doesn't Mean What You Think It Means

October 30, 2013
Time to Re-Write the Textbooks! Nature Publishes a New Version of the Citric Acid Cycle

October 29, 2013
The Khan Academy and AAMC Teach Evolution in Preparation for the MCAT

October 29, 2013
The Khan Academy and AAMC Teach the Central Dogma of Molecular Biology in Preparation for the MCAT

October 29, 2013
The Khan Academy and the Association of American Medical Colleges (AAMC) Team Up to Teach Evolution and Biochemistry for the New MCAT

October 24, 2013
ASBMB Core Concepts in Biochemistry and Molecular Biology: Matter and Energy Transformation

October 15, 2013
ASBMB Core Concepts in Biochemistry and Molecular Biology: Evolution

October 14, 2013
Fundamental Concepts in Biochemistry and Molecular Biology

October 11, 2013
ASBMB Promotes Concept Driven Teaching Strategies in Biochemistry and Molecular Biology

Another curious aspect of the theory of evolution is that everybody thinks he understands it. I mean philosophers, social scientists, and so on. While in fact very few people understand it, actually, as it stands, even as it stood when Darwin expressed it, and even less as we now may be able to understand it in biology. Jacques Monod (1974)October 8, 2013
On the Importance of Defining Evolution

October 6, 2013
Teaching Biochemistry from an Intelligent Design Creationist Perspective

October 1, 2013
The Many Definitions of Evolution

September 30. 2013
The Problems With The Selfish Gene

September 18, 2013
Breaking News!!! Wikipedia Is Wrong! (about the Central Dogma)

September 13, 2013
Sean Carroll: 'What Is Science?"

September 13, 2013
Better Biochemistry: Teaching ATP Hydrolysis for the MCAT

September 12, 2013
Better Biochemistry: Teaching to the MCAT?

June 27, 2013
The Best Enzyme

April 16, 2013
Where Do Organisms Get Their Energy?

April 10, 2013
Spontaneous Degradation of DNA

March 18, 2013
Estimating the Human Mutation Rate: Biochemical Method

Sunday, July 19, 2015

The fuzzy thinking of John Parrington: pervasive transcription

Opponents of junk DNA usually emphasize the point that they were surprised when the draft human genome sequence was published in 2001. They expected about 100,000 genes but the initial results suggested less than 30,000 (the final number is about 25,0001. The reason they were surprised was because they had not kept up with the literature on the subject and they had not been paying attention when the sequence of chromosome 22 was published in 1999 [see Facts and Myths Concerning the Historical Estimates of the Number of Genes in the Human Genome].

The experts were expecting about 30,000 genes and that's what the genome sequence showed. Normally this wouldn't be such a big deal. Those who were expecting a large number of genes would just admit that they were wrong and they hadn't kept up with the literature over the past 30 years. They should have realized that discoveries in other species and advances in developmental biology had reinforced the idea that mammals only needed about the same number of genes as other multicellular organisms. Most of the differences are due to regulation. There was no good reason to expect that humans would need a huge number of extra genes.

That's not what happened. Instead, opponents of junk DNA insist that the complexity of the human genome cannot be explained by such a low number of genes. There must be some other explanation to account for the the missing genes. This sets the stage for at least seven different hypotheses that might resolve The Deflated Ego Problem. One of them is the idea that the human genome contains thousands and thousands of nonconserved genes for various regulatory RNAs. These are the missing genes and they account for a lot of the "dark matter" of the genome—sequences that were thought to be junk.

Here's how John Parrington describes it on page 91 of his book.
The study [ENCODE] also found that 80 per cent of the genome was generating RNA transcripts having importance, many were found only in specific cellular compartments, indicating that they have fixed addresses where they operate. Surely there could hardly be a greater divergence from Crick's central dogma than this demonstration that RNAs were produced in far greater numbers across the genome than could be expected if they were simply intermediates between DNA and protein. Indeed, some ENCODE researchers argued that the basic unit of transcription should now be considered as the transcript. So Stamatoyannopoulos claimed that 'the project has played an important role in changing our concept of the gene.'
This passage illustrates my difficulty in coming to grips with Parrington's logic in The Deeper genome. Just about every page contains statements that are either wrong or misleading and when he strings them together they lead to a fundamentally flawed conclusion. In order to critique the main point, you have to correct each of the so-called "facts" that he gets wrong. This is very tedious.

I've already explained why Parrington is wrong about the Central Dogma of Molecular Biology [John Avise doesn't understand the Central Dogma of Molecular Biology]. His readers don't know that he's wrong so they think that the discovery of noncoding RNAs is a revolution in our understanding of biochemisty—a revolution led by the likes of John A. Stamatoyannopoulos in 2012.

The reference in the book to the statement by Stamatoyannopoulos is from the infamous Elizabeth Pennisi article on ENCODE Project Writes Eulogy for Junk DNA (Pennisi, 2012). Here's what she said in that article ...
As a result of ENCODE, Gingeras and others argue that the fundamental unit of the genome and the basic unit of heredity should be the transcript—the piece of RNA decoded from DNA—and not the gene. “The project has played an important role in changing our concept of the gene,” Stamatoyannopoulos says.
I'm not sure what concept of a gene these people had before 2012. It appears that John Parrington is under the impression that genes are units that encode proteins and maybe that's what Pennisi and Stamatoyannopoulos thought as well.

If so, then perhaps the publicity surrounding ENCODE really did change their concept of a gene but all that proves is that they were remarkably uniformed before 2012. Intelligent biochemists have known for decades that the best definition of a gene is "a DNA sequence that is transcribed to produce a functional product."2 In other words, we have been defining a gene in terms of transcripts for 45 years [What Is a Gene?].

This is just another example of wrong and misleading statements that will confuse readers. If I were writing a book I would say, "The human genome sequence confirmed the predictions of the experts that there would be no more than 30,000 genes. There's nothing in the genome sequence or the ENCODE results that has any bearing on the correct understanding of the Central Dogma and there's nothing that changes the correct definition of a gene."

You can see where John Parrington's thinking is headed. Apparently, Parrington is one of those scientists who were completely unaware of the fact that genes could specify functional RNAs and completely unaware of the fact that Crick knew this back in 1970 when he tried to correct people like Parrington. Thus, Parrington and his colleagues were shocked to learn that the human genome only had only 25,000 genes and many of them didn't encode proteins. Instead of realizing that his view was wrong, he thinks that the ENCODE results overthrew those old definitions and changed the way we think about genes. He tries to convince his readers that there was a revolution in 2012.

Parrington seems to be vaguely aware of the idea that most pervasive transcription is due to noise or junk RNA. However, he gives his readers no explanation of the reasoning behind such a claim. Spurious transcription is predicted because we understand the basic concept of transcription initiation. We know that promoter sequences and transcription binding sites are short sequences and we know that they HAVE to occur a high frequency in large genomes just by chance. This is not just speculation. [see The "duon" delusion and why transcription factors MUST bind non-functionally to exon sequences and How RNA Polymerase Binds to DNA]

If our understanding of transcription initiation is correct then all you need is a activator transcription factor binding site near something that's compatible with a promoter sequence. Any given cell type will contain a number of such factors and they must bind to a large number of nonfunctional sites in a large genome. Many of these will cause occasional transcription giving rise to low abundance junk RNA. (Most of the ENCODE transcripts are present at less than one copy per cell.)

Different tissues will have different transcription factors. Thus, the low abundance junk RNAs must exhibit tissue specificity if our prediction is correct. Parrington and the ENCODE workers seem to think that the cell specificity of these low abundance transcripts is evidence of function. It isn't—it's exactly what you expect of spurious transcription. Parrington and the ENCODE leaders don't understand the scientific literature on transription initiation and transcription factors binding sites.

It takes me an entire blog post to explain the flaws in just one paragraph of Parrington's book. The whole book is like this. The only thing it has going for it is that it's better than Nessa Carey's book [Nessa Carey doesn't understand junk DNA].


1. There are about 20,000 protein-encoding genes and an unknown number of genes specifying functional RNAs. I'm estimating that there are about 5,000 but some people think there are many more.

2. No definition is perfect. My point is that defining a gene as a DNA sequence that encodes a protein is something that should have been purged from textbooks decades ago. Any biochemist who ever thought seriously enough about the definition to bring it up in a scientific paper should be embarrassed to admit that they ever believed such a ridiculous definition.

Pennisi, E. (2012) "ENCODE Project Writes Eulogy for Junk DNA." Science 337: 1159-1161. [doi:10.1126/science.337.6099.1159"]

Saturday, April 27, 2013

DNA: Nature Celebrates Ignorance

Some freelance science writer named Philip Ball has published an article in the April 25, 2013 issue of Nature: Celebrate the Unknowns.

The main premise of the article is revealed in the short blurb under the title: "On the 60th anniversary of the double helix, we should admit that we don't fully understand how evolution works at the molecular level, suggests Philip Ball."

What nonsense! We understand a great deal about how evolution works at the molecular level. Perhaps Philip Ball meant to say that we don't understand the historical details of how a particular genome evolved, but even that's misleading.

I've commented before on articles written by Philip Ball. In the past, he appeared to be in competition with Elizabeth Pennisi of Science for some kind of award for misunderstanding the human genome.

SEED and the Central Dogma of Molecular Biology - I Take Back My Praise
Shoddy But Not "Junk"?

Let's look at what the article says ...

Thursday, September 13, 2012

James Shapiro Claims Credit for Predicting That Junk DNA Is Actually Part of a "highly sophisticated information storage organelle"

Do you remember James Shaprio? He's the University of Chicago scientist who claims to have discovered a new theory of evolution in his book evolution: A View from the 21st Century [see my review in NCSE Reports]. The book criticizes the old hardened version of the Modern Synthesis and never mentions things like random genetic drift or Nearly-Neutral Theory. It's difficult to imagine how someone could criticize evolutionary theory without understanding population genetics but he managed to pull it off.

You might also recall that he's the scientist who criticized the Central Dogma of Molecular Biology when he clearly didn't understand it [Revisiting the Central Dogma in the 21st Century]. I was shocked to learn that he had published a paper with the title "Revisiting the Central Dogma in the 21st Century" without ever bothering to read the literature to find out how Francis Crick actually defined the Central Dogma. (In fact, Shapiro misrepresented Crick's view.) It goes to show you how silly you look when you criticize something you don't understand.

Sunday, January 13, 2008

How Much Junk in the Human Genome?

Ryan Gregory has another contribution to this question that's well worth a read [Is most of the human genome functional?].

Among other things, Ryan picks on the views of John Mattick who has got to be one of the worst scientists in the field. Whenever I read a paper by Mattick I revise my opinion of the value of peer-reviewed literature. It's bad enough that Mattick has silly ideas but it's even sadder that his "peer" reviewers don't recognize it.

Here's a quote from Mattick that I discussed in my article on the The Central Dogma of Molecular Biology. It's obvious that he doesn't understand the real meaning of the central dogma. Can you pick out the other conceptual flaws in this paragraph? [Hints: Worst Figure Ever and Dog Ass Plots.]
The central dogma of biology holds that genetic information normally flows from DNA to RNA to protein. As a consequence it has been generally assumed that genes generally code for proteins, and that proteins fulfil not only most structural and catalytic but also most regulatory functions, in all cells, from microbes to mammals. However, the latter may not be the case in complex organisms. A number of startling observations about the extent of non-protein coding RNA (ncRNA) transcription in the higher eukaryotes and the range of genetic and epigenetic phenomena that are RNA-directed suggests that the traditional view of genetic regulatory systems in animals and plants may be incorrect.

Mattick, J.S. (2003) Challenging the dogma: the hidden layer of non-protein-coding RNAs in complex organisms. BioEssays 25:930-939.


Monday, April 20, 2009

International team cracks mammalian gene control code

International team cracks mammalian gene control code

Stop the presses! Revise the textbooks! John Mattick and his collaborators have discovered how genes are controlled in mammals.

Anyone who knows Mattick's past history will know what's coming—Mattick overthrew the Central Dogma of Molecular Biology over six years ago (Mattick, 2003; Mattick, 2004).1,2
An international consortium of scientists, including researchers from The University of Queensland (UQ), have probed further into the human genome than ever before.

They have discovered how genes are controlled in mammals, as well as the tiniest genetic element ever found.

Their discoveries will be published in three milestone papers in leading journal Nature Genetics.


1. See Basic Concepts: The Central Dogma of Molecular Biology for the truth about the Central Dogma.

2. See Greg Laden Gets Suckered by John Mattick for an example of how easy it is to get fooled by John Mattick.

Mattick, J.S. (2003) Challenging the dogma: the hidden layer of non-protein-coding RNAs in complex organisms. BioEssays 25:930-939.

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

Friday, March 16, 2012

John Mattick Wins Chen Award for Distinguished Academic Achievement in Human Genetic and Genomic Research

Shame on the Human Genome Organization (HUGO). It has awarded a prestigious prize (US $10,000) to John Mattick, director of the Centre for Molecular Biology and Biotechnology at the University of Queensland in Brisbane, Australia. Here's the report from the Sydney Morning Herald.

Making something of junk earns geneticist top award

WHEN Sydney geneticist John Mattick suggested junk DNA was anything but rubbish he was challenging an assumption that had underpinned genetics for 50 years.

''The ideas I put forward 10 years ago were quite radical but I thought I was right,'' Professor Mattick said.

He was. And tomorrow he will become the first Australian honoured with the Chen Award for distinguished academic achievement in human genetic and genomic research, awarded by the Human Genome Organisation.

For decades after James Watson and Francis Crick discovered DNA was a double helix, scientists believed most genes were the written instructions for proteins, the building blocks of all body processes. The assumption was true for bacteria but not complex organisms like humans, said Professor Mattick, the new executive director of the Garvan Institute.

In humans, more than 95 per cent of the genome contains billions of letters that do not make proteins, called non-coding DNA. ''When people bumped into all this DNA that didn't make proteins they thought it must be junk,'' he said. But Professor Mattick felt it was unlikely that useless material would survive hundreds of millions of years of evolution.

He found that the non-protein-coding sections of DNA had a function, to produce RNA.

"The obvious and very exciting possibility was that there is another layer of information being expressed by the genome - that the non-coding RNAs form a massive and previously unrecognised regulatory network that controls human development.''

Many scientists now believe this RNA is the basis of the brain's plasticity and learning, and may hold the secret to understanding many complex diseases.

Thursday, April 24, 2014

ASBMB Core Concepts in Biochemistry and Molecular Biology: Biological Information

Theme

Better Biochemistry
The American Society for Biochemistry and Molecular Biology (ASBMB) has decided that the best way to teach undergraduate biochemistry is to concentrate on fundamental principles rather than facts and details. This is an admirable goal—one that I strongly support.

Over the past few months, I've been discussing the core concepts proposed by Tansey et al. (2013) [see Fundamental Concepts in Biochemistry and Molecular Biology]. The five concepts are:
  1. evolution [ASBMB Core Concepts in Biochemistry and Molecular Biology: Evolution ]
  2. matter and energy transformation [ASBMB Core Concepts in Biochemistry and Molecular Biology: Matter and Energy Transformation]
  3. homeostasis [ASBMB Core Concepts in Biochemistry and Molecular Biology: Homeostasis]
  4. biological information [ASBMB Core Concepts in Biochemistry and Molecular Biology: Biological Information]
  5. macromolecular structure and function [ASBMB Core Concepts in Biochemistry and Molecular Biology: Molecular Structure and Function]

Thursday, July 06, 2023

James Shapiro doesn't like junk DNA

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

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

Friday, May 07, 2021

More misinformation about junk DNA: this time it's in American Scientist

Emily Mortola and Manyuan Long have just published an article in American Scientist about Turning Junk into Us: How Genes Are Born. The article contains a lot of misinformaton about junk DNA that I'll discuss below.

Emily Mortola is a freelance science writer who worked with Manyuan Long when she was an undergraduate (I think). Manyuan Long is the Edna K. Papazian Distinguished Service Professor of Ecology and Evolution in the Department of Ecology and Evolution at the University of Chicago. His main research interest is the origin of new genes. It's reasonable to suspect that he's an expert on genome structure and evolution.

The article is behind a paywall so most of you can't see anything more than the opening paragraphs so let's look at those first. The second sentence is ...

As we discovered in 2003 with the conclusion of the Human Genome Project, a monumental 13-year-long research effort to sequence the entire human genome, approximately 98.8 percent of our DNA was categorized as junk.

This is not correct. The paper on the finished version of the human genome sequence was published in October 2004 (Finishing the euchromatic sequence of the human genome) and the authors reported that the coding exons of protein-coding genes covered about 1.2% of the genome. However, the authors also noted that there are many genes for tRNAs, ribosomal RNAs, snoRNAs, microRNAs, and probably other functional RNAs. Although they don't mention it, the authors must also have been aware of regulatory sequences, centromeres, telomeres, origins of replication and possibly other functional elements. They never said that all noncoding DNA (98.8%) was junk because that would be ridiculous. It's even more ridiculous to say it in 2021 [Stop Using the Term "Noncoding DNA:" It Doesn't Mean What You Think It Means].

The part of the article that you can see also lists a few "Quick Takes" and one of them is ...

Close to 99 percent of our genome has been historically classified as noncoding, useless “junk” DNA. Consequently, these sequences were rarely studied.

This is also incorrect as many scientists have pointed out repeatedly over the past fifty years or so. At no time in the past 50 years has any knowledgeable scientist ever claimed that all noncoding DNA is junk. I'm sorely tempted to accuse the authors of this article of lying because they really should know better, especially if they're writing an article about junk DNA in 2021. However, I reluctantly defer to Hanlon's razor.

Mortola and Long claim that mammalian genomes have between 85% to 99% junk DNA and wonder if it could have a function.

To most geneticists, the answer was that it has no function at all. The flow of genetic information—the central dogma of molecular biology—seems to leave no role for all of our intergenic sequences. In the classical view, a gene consists of a sequence of nucleotides of four possible types--adenine, cytosine, guanine, and thymine--represented by the letters A, C, G, and T. Three nucleotides in a row make up a codon, with each codon corresponding to a specific amino acid, or protein subunit, in the final protein product. In active genes, harmful mutations are weeded out by selection and beneficial ones are allowed to persist. But noncoding regions are not expressed in the form of a protein, so mutations in noncoding regions can be neither harmful nor beneficial. In other words, "junk" mutations cannot be steered by natural selection.

Those of you who have read this far will cringe when reading that. There are so many obvious errors in that paragraph that applying Hanlon's razor seems very complimentary. Imagine saying in the 21st centurey that the Central Dogma leaves no role at all for regulatory sequences or ribosomal RNA genes! But there's more; the authors double-down on their incorrect understanding of "gene" in order to fit their misunderstanding of the Central Dogma.

What Is a Gene, Really?

In our de novo gene studies in rice, to truly assess the potential significance of de novo genes, we relied on a strict definition of the word "gene" with which nearly every expert can agree. First, in order for a nucleotide sequence to be considered a true gene, an open reading frame (ORF) must be present. The ORF can be thought of as the "gene itself"; it begins with a starting mark common for every gene and ends with one of three possible finish line signals. One of the key enzymes in this process, the RNA polymerase, zips along the strand of DNA like a train on a monorail, transcribing it into its messenger RNA form. This point brings us to our second important criterion: A true gene is one that is both transcribed and translated. That is, a true gene is first used as a template to make transient messenger RNA, which is then translated into a protein.

Five Things You Should Know if You Want to Participate in the Junk DNA Debate

The authors admit in the next paragraph that some pseudogenes may produce functional RNAs that are never translated into proteins but they don't mention any other types of gene. I can understand why you might concentrate on protein-coding genes if you are studying de novo genes but why not just say that there are two types of genes and either one can arise de novo? But there's another problem with their definition: they left out a key property of a gene. It's not sufficient that a given stretch of DNA is transcribed and the RNA is translated to make a protein: the protein has to have a function before you can say that the stretch of DNA is a gene [What Is a Gene?]. We'll see in a minute why this is important.

The main point of the paper is the birth of de novo genes and the authors discuss their work with the rice genome. They say they've discovered 175 de novo genes but they don't say how many have a real biological function. This is an important problem in this field and it would have been fascinating to see a description of how they go about assigning a function to their, mostly small, pepides [The evolution of de novo genes]. I'm guessing that they just assume a function as soon as they recognize an open reading frame in a transcript.

As you can see from the title of the article, the emphasis is on the idea that de novo genes can arise from junk DNA—a concept that's not seriously disputed. The one good thing about the article is that the authors do not directly state that the reason for junk DNA is to give rise to new genes but this caption is troubling.

The Human Genome Project was a 13-year-long research effort aimed at mapping the entire human genetic sequence. One of its most intriguing findings was the observation that the number of protein-coding genes estimated to exist in humans--approximately 22,300--represents a mere 1.2 percent of our whole genome, with the other 98.8 percent being categorized as noncoding, useless junk. Analyses of this presumed junk DNA in diverse species are now revealing its role in the creation of genes.

Why do science writers continue to spread misinformation about junk DNA when there's so much correct information out there? All you have to do is look [More misconceptions about junk DNA - what are we doing wrong?].


Thursday, August 09, 2012

Still Digging: Part I

Believe it or not, the IDiots are still trying to weasel out of the mistakes they've made in attacking junk DNA.

Here's the problem. Jonathan Wells wrote an entire book on The Myth of Junk DNA. Wells says that back in the early 1970s a substantial number of scientists—he calls them Darwinists—said that all noncoding DNA was junk.

Friday, December 16, 2022

Can the AI program ChatGPT pass my exam?

There's a lot of talk about ChatGPT and how it can prepare lectures and get good grades on undergraduate exams. However, ChatGPT is only as good as the information that's popular on the internet and that's not always enough to get a good grade on my exam.

ChatGPT is an artificial intelligence (AI) program that's designed to answer questions using a style and language that's very much like the responses you would get from a real person. It was developed by OpenAI, a tech company in San Francisco. You can create an account and log in to ask any question you want.

Several professors have challenged it with exam questions and they report that ChatGPT would easily pass their exams. I was skeptical, especially when it came to answering questions on controversial topics where there was no clear answer. I also suspected that ChatGPT would get it's answers from the internet and this means that popular, but incorrect, views would likely be part of ChatGPT's response.

Here are my questions and the AI program's answers. It did quite well in some cases but not so well in others. My main concern is that programs like this might be judged to be reliable sources of information despite the fact that the real source is suspect.

Thursday, February 16, 2023

Birds of a feather: epigenetics and opposition to junk DNA

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

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

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

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

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

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

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

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


Wednesday, July 31, 2013

The Dark Matter Rises

John Mattick is a Professor and research scientist at the Garvan Institute of Medical Research at the University of New South Wales (Australia).

John Mattick publishes lots of papers. Most of them are directed toward proving that almost all of the human genome is functional. I want to remind you of some of the things that John Mattick has said in the past so you'll be prepared to appreciate my next post [The Junk DNA Controversy: John Mattick Defends Design].

Mattick believes that the Central Dogma means DNA makes RNA makes protein. He believes that scientists in the past took this very literally and discounted the importance of RNA. According to Mattick, scientists in the past believed that genes were the only functional part of the genome and that all genes encoded proteins.

If that sounds familiar it's because there are many IDiots who make the same false claim. Like Mattick, they don't understand the Central Dogma of Molecular Biology and they don't understand the history that they are distorting.

Mattick believes that there is a correlation between the amount of noncoding DNA in a genome and the complexity of the organism. He thinks that the noncoding DNA is responsible for making tons of regulatory RNAs and for regulating expression of the genes. This belief led him to publish a famous figure (left) in Scientific American.

Mattick has many followers. So many, in fact, that the Human Genome Organization (HUGO) recently gave him an award for his contributions to the study of the human genome. Here's the citation.
Theme
Genomes
& Junk DNA
The Award Reviewing Committee commented that Professor Mattick’s “work on long non-coding RNA has dramatically changed our concept of 95% of our genome”, and that he has been a “true visionary in his field; he has demonstrated an extraordinary degree of perseverance and ingenuity in gradually proving his hypothesis over the course of 18 years.”
Let's see what this "true visionary" is saying this year. The first paper is "The dark matter rises: the expanding world of regulatory RNAs" (Clark et al., 2013). Here's the abstract ...
The ability to sequence genomes and characterize their products has begun to reveal the central role for regulatory RNAs in biology, especially in complex organisms. It is now evident that the human genome contains not only protein-coding genes, but also tens of thousands of non–protein coding genes that express small and long ncRNAs (non-coding RNAs). Rapid progress in characterizing these ncRNAs has identified a diverse range of subclasses, which vary widely in size, sequence and mechanism-of-action, but share a common functional theme of regulating gene expression. ncRNAs play a crucial role in many cellular pathways, including the differentiation and development of cells and organs and, when mis-regulated, in a number of diseases. Increasing evidence suggests that these RNAs are a major area of evolutionary innovation and play an important role in determining phenotypic diversity in animals.
This is his main theme. Mattick believes that a large percentage of the human genome is devoted to making regulatory RNAs that control development. He believes that the evolution of this complex regulatory network is responsible for the creation of complex organisms like humans, which, incidentally, are the pinnicle of evolution according to the figure shown above.

The second paper I want to highlight focuses on a slightly different theme. It's title is "Understanding the regulatory and transcriptional complexity of the genome through structure." (Mercer and Mattick, 2013). In this paper he emphasizes the role of noncoding DNA in creating a complicated three-dimensional chromatin structure within the nucleus. This structure is important in regulating gene expression in complex organisms. Here's the abstract ...
An expansive functionality and complexity has been ascribed to the majority of the human genome that was unanticipated at the outset of the draft sequence and assembly a decade ago. We are now faced with the challenge of integrating and interpreting this complexity in order to achieve a coherent view of genome biology. We argue that the linear representation of the genome exacerbates this complexity and an understanding of its three-dimensional structure is central to interpreting the regulatory and transcriptional architecture of the genome. Chromatin conformation capture techniques and high-resolution microscopy have afforded an emergent global view of genome structure within the nucleus. Chromosomes fold into complex, territorialized three-dimensional domains in concert with specialized subnuclear bodies that harbor concentrations of transcription and splicing machinery. The signature of these folds is retained within the layered regulatory landscapes annotated by chromatin immunoprecipitation, and we propose that genome contacts are reflected in the organization and expression of interweaved networks of overlapping coding and noncoding transcripts. This pervasive impact of genome structure favors a preeminent role for the nucleoskeleton and RNA in regulating gene expression by organizing these folds and contacts. Accordingly, we propose that the local and global three-dimensional structure of the genome provides a consistent, integrated, and intuitive framework for interpreting and understanding the regulatory and transcriptional complexity of the human genome.
Other posts about John Mattick.

How Not to Do Science
John Mattick on the Importance of Non-coding RNA
John Mattick Wins Chen Award for Distinguished Academic Achievement in Human Genetic and Genomic Research
International team cracks mammalian gene control code
Greg Laden Gets Suckered by John Mattick
How Much Junk in the Human Genome?
Genome Size, Complexity, and the C-Value Paradox


Clark, M.B., Choudhary, A., Smith, M.A., Taft, R.J. and Mattick, J.S. (2013) The dark matter rises: the expanding world of regulatory RNAs. Essays in Biochemistry 54:1-16. [doi:10.1042/bse0540001]

Mercer, T.R. and Mattick, J.S. (2013) Understanding the regulatory and transcriptional complexity of the genome through structure. Genome research 23:1081-1088 [doi: 10.1101/gr.156612.113]

Sunday, November 18, 2018

Revisiting the deflated ego problem

Humans are just another animal. All animals share a core set of several thousand genes and all mammals have about the same number of homologous genes (~25,000). The differences between species such as gorillas, bats and whales are due almost exclusively to differences in the timing of expression of these common genes.

This concept is not new. It was the major theme of Stephen Jay Gould's book, Ontogeny and Phylogeny, back in 1977 [Learning About EVO-Devo]. Over the next twenty years or so, the concept was confirmed repeatedly by the work of hundreds of developmental biology labs working mostly with model organisms such as Drosophila (fruit flies). The field is evolutionary developmental biology or "evo-devo" and that work has been nicely summarized in several popular books appearing in the 21st century.

Wednesday, March 11, 2015

A physicist tries to understand junk DNA: Part II

Yesterday I posted some comments on a blog post by physicist Rob Sheldon [A physicist tries to understand junk DNA ]. My comments were based on what I had seen on Uncommon Descent but it turns out that was only a summary of a longer post that appeared on Evolution News & Views (sic): More on Junk DNA and the "Onion Test".

The longer post doesn't add very much to the argument but it does have something interesting at the bottom. Here's what Rob Sheldon says about the Onion Test and junk DNA.

Sunday, January 04, 2015

A physiologist thinks about evolution

Denis Noble is a physiologist at Oxford University (now Professor Emeritus). He is famous for his work on the physiology of the heartbeat and he is touted as one of the founders of systems biology.

Denis Noble wrote a book on evolutionary theory called The Music of Life. It's featured on The Third Way, a website created by James Shapiro to promote his version of a paradigm shift in thinking about evolution. All the usual suspects are represented on that site.1

Here's how the book is described on that website ....
What is Life? Decades of research have resulted in the full mapping of the human genome - three billion pairs of code whose functions are only now being understood. The gene’s eye view of life, advocated by evolutionary biology, sees living bodies as mere vehicles for the replication of the genetic codes.

But for a physiologist, working with the living organism, the view is a very different one. Denis Noble is a world renowned physiologist, and sets out an alternative view to the question - one that becomes deeply significant in terms of the living, breathing organism. The genome is not life itself. Noble argues that far from genes building organisms, they should be seen as prisoners of the organism.

The view of life presented in this little, modern, post-genome project reflection on the nature of life, is that of the systems biologist: to understand what life is, we must view it at a variety of different levels, all interacting with each other in a complex web. It is that emergent web, full of feedback between levels, from the gene to the wider environment, that is life. It is a kind of music.

Including stories from Noble’s own research experience, his work on the heartbeat, musical metaphors, and elements of linguistics and Chinese culture, this very personal and at times deeply lyrical book sets out the systems biology view of life.
I haven't read this book and I don't intend to read it. Having listened to a lecture by Denis Noble (below) I don't think I'm going to learn anything more by buying the book.

I urge you to watch the lecture. It's the plenary lecture at the International Conference of Physiological Sciences in November, 2012. Denis Noble is the President of the International Union of Physiological Sciences. The lecture is only 30 minutes long but it gives you a good introduction to the way many scientists from outside the field of evolutionary biology are thinking about evolution (and the Central Dogma of Molecular Biology). It's not a very pretty picture.


If you want a brief summary of what's wrong with this lecture see Jerry Coyne's blog website post: Famous physiologist embarrasses himself by claiming that the modern theory of evolution is in tatters.


1. For more on James Shapiro see: The Third Fourth? Way
Evolution: a View from the 21st century
Reply to Laurence A Moran’s review of Evolution: A View from the 21st Century
James Shapiro Responds to My Review of His Book
James Shapiro Never Learns
James Shapiro Claims Credit for Predicting That Junk DNA Is Actually Part of a "highly sophisticated information storage organelle"
Revisiting the Central Dogma in the 21st Century.

Tuesday, March 22, 2016

How do you characterize these scientists?

We've been having a discussion on another thread about ID proponents. Are some of them acting in good faith or are they all lying and deceiving their followers?

I have similar problems about many scientists. I've been reading up on pervasive transcription and the potential number of genes for noncoding, functional, RNAs in the human genome. As far as I can tell, there are only a few hundred examples that have any supporting evidence. There are good scientific reasons to believe that most of the detected transcripts are junk RNA produced as the result of accidental, spurious, transcription.

There are about 20,000 protein-coding genes in the human genome. I think it's unlikely that there are more than a few thousand genes for functional RNAs for a total of less than 25,000 genes.

Here's one of the papers I found.
Guil, S. and Esteller, M. (2015) RNA–RNA interactions in gene regulation: the coding and noncoding players. Trends in Biochemical Sciences 40:248-256. [doi: 10.1016/j.tibs.2015.03.001]
Trends in Biochemical Sciences is a good journal and this is a review of the field by supposed experts. The authors are from the Department of Physiological Sciences II at the University of Barcelona School of Medicine in Barcelona, Catalonia, Spain. The senior author, Manel Esteller, has a Wikipedia entry [Manel Esteller].

Here's the first paragraph of the introduction.
There are more genes encoding regulatory RNAs than encoding proteins. This evidence, obtained in recent years from the sum of numerous post-genomic deep-sequencing studies, give a good clue of the gigantic step we have taken from the years of the central dogma: one gene gives rise to one RNA to produce one protein.
The first sentence is not true by any stretch of the imagination. The best that could be said is that there "may" be more genes for regulatory RNAs (> 20,000) but there's no strong consensus yet. Since the first sentence is an untruth, it follows that it is incorrect to say that the evidence supports such a claim.

It's also untrue to distort the real meaning of the Central Dogma of Molecular Biology, which never said that all genes have to encode proteins. The authors don't understand the history of their field in spite of the fact they are writing a review of that field.

Here's the problem. Are these scientists acting in good faith when they say such nonsense? Does acting in "good faith" require healthy criticism and critical thinking or is "honesty" the only criterion? The authors are clearly deluded about the controversy since they assume that it has been resolved in favor of their personal biases but they aren't lying. Can we distinguish between competent science and bad science based on such statements? Can we say that these scientists are incompetent or is that too harsh?

Furthermore, what ever happened to peer review? Isn't the system supposed to prevent such mistakes?


Saturday, December 15, 2007

What the Sickest Are Saying

Dr. Sharon Moalem is the lead author of a book called Survival of the Sickest. According to his website, Sharon Moalem got his Ph.D. "in the emerging fields of neurogenetics and evolutionary medicine from the University of Toronto." He now works at Mount Sinai School of Medicine in New York City (USA).

It looks like a fascinating book (not).
This revelatory book explains how, especially when you take the evolutionary long-view, many diseases are really complicated blessings, not simple curses. Survival of the Sickest answers the riddles behind many diseases that seem to be inexplicably wired into our genetic code, starting with the biggest riddle of them all: If natural selection is supposed to get rid of harmful genetic traits, why are hereditary diseases so common?

Through a fresh and engaging examination of our evolutionary history, Dr. Sharon Moalem reveals how many of the conditions that we think of as diseases today actually gave our ancestors a leg up in the survival sweepstakes. When the option is a long life with a disease or a short one without it, evolution opts for the long ball every time.

Survival of the Sickest explores earth, history, and the human genome to discover how environmental, cultural, and genetic differences shaped us through evolution and continue to play an active role in our health today.
Sharon Maolem has a blog and I was attracted to it today when he linked to my article on the Central Dogma of Molecular Biology. Here's what he says today about junk DNA [Please Take the Junk Out of DNA].
I still cringe whenever I see someone refer to parts of genome as junk or junk DNA. What they are talking about really is areas of DNA that we still don’t fully understand what their function might be. The idea of junk came out of the central dogma (this is not some Politburo manifesto) because some people erroneously believed that if DNA wasn’t used to make a functional protein than it must be like Grandma’s plastic covered couch, junk. Turns out that far from being junk, the really interesting part of our genome may be the part no one really thought to look at which is great for anyone interested in antiques since most of our DNA was previously relegated to the trash bin of evolution.
I've started to set him straight over on Dr. Sharon's Blog. In case it doesn't take the first time, some of you might like to continue his education in basic molecular biology. Looks like he'll need it for his second book.


Tuesday, October 16, 2018

John Mattick's latest attack on junk DNA

John Mattick is the most prominent defender of the idea that the human genome is full of functional sequences. In fact, he is just about the only scientist of any prominence who's on that side of the debate. His main "evidence" is the fact that genomes are pervasively transcribed and that most of the transcripts are functional. Let's look at his latest review paper to see how well this argument stands up to close scrutiny (Mattick, 2018).1

As you read this post, keep in mind that in 2012 John Mattick was awarded a prize by the Human Genome Organization for proving his hypothesis [John Mattick Wins Chen Award for Distinguished Academic Achievement in Human Genetic and Genomic Research].
The Award Reviewing Committee commented that Professor Mattick’s “work on long non-coding RNA has dramatically changed our concept of 95% of our genome”, and that he has been a “true visionary in his field; he has demonstrated an extraordinary degree of perseverance and ingenuity in gradually proving his hypothesis over the course of 18 years.”
Mattick follows his usual format by giving us his version of history. He has argued for the past 15 years that the scientific community has been reluctant to accept the evidence of massive amounts of regulatory RNA genes because it conflicts with the standard paradigm of the supremacy of proteins. In the past he has claimed that this paradigm is based on the Central Dogma which states, according to him, that the only real function of DNA is to make proteins [How Much Junk in the Human Genome?]. As we shall see, he hasn't abandoned that argument but at least he no longer refers to the Central Dogma for support