Showing posts sorted by date for query central dogma. Sort by relevance Show all posts
Showing posts sorted by date for query central dogma. Sort by relevance Show all posts
Thursday, July 17, 2025
Predatory journals are helping to spread misinformation in the scientific literature
Thursday, May 22, 2025
Is AI really "intelligent"? Here are 13 biology questions to test the latest AI algorithms.
Here's the problem. I can only access the cheap versions of AI such as ChatGPT and Scite Assistant but I can also see the results of Google's Generative AI whenever I do a Google search. Chris has access to more sophisticated versions so that's what he might be referring to when he says they operate at the Ph.D. level of intelligence.
Wednesday, February 05, 2025
Why Trust Science?
In this essay, we address the question of why we can trust science—and how we can identify which scientific claims we can trust. We begin by explaining how scientists work together, as part of a larger scientific community, to generate knowledge that is reliable. We describe how the scientific process builds a consensus, and how new evidence can change the ways that scientists—and, ultimately, the rest of us—see the world. Last, but not least, we explain how, as informed citizens, we can all become “competent outsiders” who are equipped to evaluate scientific claims and are able to separate science facts from science fiction.
Most of the essay describes an idealized version of how science works with an emphasis on collaboration and rigorous oversight. They claim that the work of scientists can usually be trusted because it is self-correcting.
Friday, December 06, 2024
William Haseltine misrepresents molecular biology and calls for a paradigm shift
A New Dogma Of Molecular Biology: A Paradigm Shift by William A. Haseltine
Wednesday, October 23, 2024
Santi Garcia-Vallvé reviews my book
Santi Garcia-Vallvé has reviewed my book in the journal Mètode. It's written in Catalan but Santi was kind enough to send me a translation.
OUR GENOME HAS NOT YET SPOKEN ITS LAST WORDWhat's in Your Genome? 90% of Your Genome Is Junk. Laurence A. Moran. Aevo University of Toronto Press (UTP). May 2023. 392 pages.
What's in Your Genome? exposes a variety of topics and concepts in molecular biology, genetics, and evolution that have been misunderstood by scientists and the general public. Many of these concepts are widely accepted, despite ongoing debate about them. Although the author, Larry Moran, has exhaustively discussed most of these issues on his blog "Sandwalk: Strolling with a sceptical biochemist", discussing them in a book allows for a more in-depth investigation.
One of these recurring themes is Francis Crick 's 1957 proposal of the Central Dogma of Molecular Biology. In his book Molecular Biology of the gene, James Watson adapted this concept by summarizing in a figure the flow of genetic information from DNA to RNA and then to proteins. This version was widely adopted, and many scientists now assume that it was the original definition. However, Crick claimed that once the information had been transferred to the proteins, it could not be returned to nucleic acids. Other controversial topics discussed in the book include the number of genes encoded in the human genome, the concept of Junk DNA and the prevalence of alternative splicing in the transcription of the human genome. Larry takes a certain viewpoint on all these problems, as evidenced by the title of the book, but he also presents arguments from all sides. Throughout the book, he argues that scientists must present evidence in support of and against their findings, as well as contextualise their discoveries in light of the knowledge of the subject. Thus, the first chapters of the book describe in depth the basic ideas of genetics, genetics and evolution that are required to understand the arguments that he will present later, showing also when and how they were discovered.
This is a highly recommendable book that pushed us to think about how research findings are explained and the importance of placing them in their proper context. The media frequently looks for stunning headlines and there is growing demand to assess the social impact of a project, article or scientific project. However, if we exaggerate our findings, we risk exacerbating further diminishing the general lack of interest in scientific news. Everyone is responsible that this does not happen.
Santi Garcia-Vallvé is an associate professor in the Department of Biochemistry and Biotechnology at Rovira i Virgili University (URV) in Tarragona, Spain, and a member of the Chemoinformatics and Nutrition research group."
Philip Ball doesn't understand sloppy genomes
... anything found to be true of E.coli must also be true of Elephants.
Jacques Monod (1961)
The diversity of types remained even so, and there was no getting around the fact that a great many macroscopic structural patterns, radically unlike one another, coexist in the biosphere. A blue alga, an infusorium, an octopus, and a human being—what had they in common? With the discovery of the cell and the advent of cellular theory a new unity could be seen under this diversity. But it was some time before advances in biochemistry, mainly during the second quarter of this century, revealed the profound and strict oneness, on the microscopic level, of the whole of the living world. Today we know that from a bacterium to man the chemical machinery is essentially the same, in both its structure and its functioning.
Monod was making a case for life as a chemical process and he reflected the view of the 'phage group who were studying bacteria and bacteriophage. He argued that all living things would consist of the same basic chemicals such as lipids, nucleic acids, proteins, and carbohydrates. He also assumed that all living things would have similar networks of metabolic enzymes and contain similar pathways. These enzymes would be regulated by similar mechanisms, such as allosteric regulation, and they would be composed of the same 20 amino acids. He expected all living cells would have similar mechanisms for capturing energy and they would obey the fundamental laws of thermodynamics.
He assumed that the genetic code would be universal and that the process of protein synthesis would be essentially the same in all species. He assumed that the fundamentals of transcription and DNA replication would be the same in all species. He imagined that the basic principles of gene regulation that were worked out in bacteria would apply to eukaryotes. This included the action of transcription factors and more unusual regulatory molecules such as the regulatory RNAs discovered in 'phage and bacteria. He expected that genes, regulatory sequences, origins of replication, and other important genetic elements would be found in the DNA molecules of the genome.
I'm sure that Monod was not upset to learn that some genes had introns or that eukarotic chromatin is more complicated than the DNA-protein complexes found in bacteria. He would not have been shocked to learn that many eukaryotes have more functional RNAs than E. coli or bacteriophage λ. Junk DNA was not a problem for someone who understood evolution.
I think Monod reflected the dominant view of most knowledgeable biochemists and molecular biologists of the 1960s and 1970s.
Over the next 50 years we learned a lot more about complex eukaryotes and the dominant theme at the molecular level is that they contain lots of junk DNA and lots of overly complex structures that only make sense in light of evolution. There's a lot of sloppiness in eukaryotes, including genomes full of transposon fossils, aberrant transcription, pseudogenes, inefficient splicing, and promiscuous enzymes. A lot of this sloppiness was apparent in the 1970s, including the fact that junk DNA must contain thousands of ineffective transcription factor binding sites. We learned in the 1980s that some structures, such as the spliceosome, could only have arisen by evolution since no designer in their right mind would have built such a thing.
I would be quite proud to have served on the committee that designed the E. coli genome. There is, however, no way that I would admit to serving on a committee that designed the human genome. Not even a university committee could botch something that badly. David Penny
I got this quote from Dan Graur who credits it to David Penny as a personal communication. Graur used it in his scathing criticism of ENCODE researchers after they declared the death of junk DNA (Graur et al., 2013). The meaning is clear. The E. coli genome is compact and carries all the information needed to ensure the survival and evolution of the bacterium. It has one copy of most protein-coding genes, two copies of ribosomal RNA genes, and a minimal number of tRNA genes. The regulatory sequences are just big enough for efficient transcription under the appropriate conditions. Many genes are clustered in operons to save space. There's only one origin of replication and one terminator sequence. There's only one chromosome and it is efficiently segregated to each daughter cell after DNA replication and cell division. There are only a small number of regulatory RNA genes in E. coli.
This is why David Penny would not be proud to have served on the committee that designed the human genome. Neither would I, and that's why I spent so much time explaining sloppy genomes in my book. The idea of a sloppy genome is a difficult concept to grasp so I devoted the final chapter (Chapter 11) to the art of coping with this issue.
Now let's look at how Philip Ball handles this information on pages 116-117 of his book How Life Works.
These differences in the relative proportions of coding and non-coding DNA for simpler and more complex organisms reflect fundamental distinctions in how these organisms work. The problem has been delightfully, if inadvertently, stated by theoretical biologist David Penny. "I would be quite proud to have served on the committee that designed the E. coli genome" he has said. "There is, however, no way that I would admit to serving on a committee that designed the human genome. Not even a university committee could botch something that badly."I'd suggest that can be rephrased: "I can understand how the E. coli genome works. I cannot make any sense of how the human genome works." So the corollary of Penny's comment is rather profound: how E. coli works is not how humans work. But his quip betrays an understandable frustration that the workings of the human genome are inscrutable to us. And I fear that the remark carries the same bias as that which leads us to insist that a foreign language we find difficult to learn is unnecessarily perverse and even absurd.
This shift in perspective challenges a famous statement by Jacques Monod: "What is true for E. coli is true for the elephant." In fairness, Monod had in mind here the notion of how DNA encodes proteins—for indeed it does so in (roughly) the same way in bacteria as in pachyderms, insofar as it uses the same genetic code. But the implication in Monod's comment is that this is what really matters in the same spirit as Crick's Central Dogma. We can now see that Monod's quote is misleading in an important sense, because what matters for E. coli is not the same as what matters for an elephant. The bacterium has a genome dedicated mostly to making proteins. The elephant has a genome dedicated mostly to making noncoding RNAs with regulatory functions. To truly understand how the elephant—and the human—works, we need to untangle the mechanisms governing this regulation.
As Morris and Mattick say,
It appears that we may have fundamentally misunderstood the nature of the genetic programming in complex organisms because of the assumption that most genetic information is transacted by proteins. This may be largely true in simpler organisms, but is turning out not to be the case in more complex organisms, whose genomes appear to be progressively dominated by regulatory RNAs that orchestrate the epigenetic trajectories of differentiation and development.Or as biochemist Danny Licatalosi and neuroscientist Robert Darnell put it, biological complexity "has RNA at its core."
I think this is an excellent illustration of the differing viewpoints of Philip Ball and many biochemists and molecular biologists. David Penny and the rest of us don't disparage the human genome because we don't understand it. Quite the contrary. We think we DO understand evolution and the basic principles of molecular biology and that's why we recognize a sloppy genome when we see it. Philip Ball just can't get his head around the fact that we aren't ignorant of functional non-coding RNAs ... we just don't believe Mattick and ENCODE when they claim, without evidence, that the human genome is full of non-coding genes modulating some sophisticated regulation of the protein-coding genes.
Not only does such a model lack support but it doesn't make any sense. Why would all the 10,000 or so housekeeping genes require such regulation in humans and not in yeast? Why would evolution have selected for regulatory RNAs acting on the genes for the glycolytic enzymes? What kind of selective advantage would there have to be in order to evolve a regulatory RNA gene that could tweek expression by a few percent?
"Ball is one of the most meticulous, precise science writers out there. He is the antithesis of hypey, "dumb-it-down" reporting. He is MUCH more credible than you are, Laurence."
John Horgan July, 2024Philip Ball even wants to twist the Monod quote to fit his agenda on the importance of proteins. That's not what Monod meant. But let's think about this for a minute. The biochemists of the last century discovered a complex network of metabolic pathways with reactions that were catalyzed almost exclusively by protein enzymes. That hasn't changed. It's true of E. coli and it's true of elephants.
They also discovered that the expression of genes, especially at the level of transcription, was mostly controlled and regulated by proteins; namely, RNA polymerase and transcription factors. That hasn't changed. The expression of elephant and human genes is also regulated by transcription factors and RNA polymerase. Hundreds of studies of particular mammalian genes have demonstrated beyond a doubt that we can explain most regulation by such a model.
That doesn't mean that proteins are the only players in regulation. Over the past several decades we've discovered a variety of regulatory RNAs and we now know that there are more of these non-coding genes in humans than in bacteria. We don't know how many but so far the number of well-characterized examples amounts to fewer than 2000 genes and probably less than 1000. Note that I said "well-characterized" examples and that means that the individual RNA molecule has been studied and its biologically relevant function has been confirmed. That's not the same as a genomics study that simply identifies candidate transcripts that may or may not have a function.
Proteins still play the most important functional roles in metabolism and gene expression but they are not the only players. We've known that for 50 years. The only thing that's changed is that there may be as many as two thousand non-coding genes in humans and only a dozen or so in E. coli and the human genome may be a lot more sloppy than bacterial genomes. That's not a paradigm shift.
Note: Philip Ball was an editor at Nature and that's ironic because it's the failure of Nature editors to do their job in 2012 that got us into the mess we're in today. The editors not only allowed ENCODE researchers to make exaggerated claims about junk DNA but they actively supported and participated in the publicity campaign that sold those false claims to the general public. Nature editors have never apologized for their behavior in 2012; in fact, one of them, Magdalena Skipper, has been promoted to editor-in-chief. [The 10th anniversary of the ENCODE publicity campaign fiasco]
Friedman, H.C. (2004) From Butyribacterium to E. coli: An Essay on Unity in Biochemistry. Perspectives in Biology and Medicine 47:47-66. doi: 10.1353/pbm.2004.0007
Graur, D., Zheng, Y., Price, N., Azevedo, R.B., Zufall, R.A. and Elhaik, E. (2013) On the immortality of television sets:“function” in the human genome according to the evolution-free gospel of ENCODE. Genome Biology and Evolution 5:578-590. doi: doi: 10.1093/gbe/evt028
Monday, October 21, 2024
Philip Ball strikes back
In order to build the case for revolution, he tries to demonstrate a paradigm shift in our view of molecular biology by showing a huge gap between the understanding of previous generations of molecular biologists and the post-genomic view. I believe he is wrong about this for two reasons: first, he misrepresents the views of older molecular biologists and, second he misrepresents the discoveries of the past twenty years. I tried to explain why he was wrong about these two claims in a previous post where I discussed an article he published in Scientific American in May 2024: Philip Ball says RNA may rule our genome.
Philip Ball responded to my criticism in a comment under that article.
Older molecular biologists were really stupid
I said ...
Ball begins with the same old myth that writers like him have been repeating for many years. He claims that before ENCODE most molecular biologists were really stupid. According to Philip Ball, most of us thought that coding DNA was the only functional part of the genome and most of the rest was junk DNA.
In the comment section of my earlier post, Philip Ball says,
I’m sorry to say that Larry’s commentary here is dismayingly inaccurate.
Let’s get this one out of the way first:
“He claims that before ENCODE most molecular biologists were really stupid.”
I have never made this claim and never would – it is a pure fabrication on Larry’s part. I guess this is what John Horgan meant in his comment to Larry: credible writers don’t just make up stuff.
I admit that Philip Ball never said those exact words. I'll leave it to the readers to decide whether my characterization of his position is accurate.
I stand by the statements I made although I admit to a bit of hyperbole. Ball has said repeatedly that the molecular biologists of my generation were wedded to the idea that coding regions were the only important part of the genome and he often connects that to the Central Dogma of Molecular Biology. He also claims that the experts in molecular biology dismissed all non-coding DNA as junk. Here's how he puts it in another article that he published recently in Aeon: We are not machines.
Only around 1-2 per cent of the entire human genome actually consists of protein-coding genes. The remainder was long thought to be mostly junk: meaningless sequences accumulated over the course of evolution. But at least some of that non-coding genome is now known to be involved in regulating genes: altering, activating or suppressing their transcription in RNA and translation into proteins.
I interpret that to mean that older molecular biologists, like me, didn't know about functional non-coding DNAs such as centromeres, telomeres, origins of replication, non-coding genes, SARs, and regulatory sequences in spite of the fact that thousands of papers on these sequences were published in the 30 years that preceded the publication of the first draft of the human genome sequence. This is not true, we did know about those things. I don't think it's too much of an exaggeration to say that Philip Ball thinks we were really stupid.
Here's what he says in his book, "How Life Works" (p. 85) when he's talking about the beginning of the human genome project.
Even at its outset, it faced the somewhat troubling issue that just 2 percent or so of our genome actually accounts for protein-coding genes. The conventional narrative was that our biology was all about proteins, for each of which the genome held the template. ... But we had all this other DNA too! What was it for? The common view was that it was mostly just junk, like the stuff in our attics: meaningless material accumulated during evolution, which our cells had no motivation to clear out.
Again, his claim is that in 1990 at the beginning of the human genome project the experts in molecular biology thought that non-coding DNA was mostly junk (98% of the genome). I have repeatedly refuted this myth and challenged anyone to come up with a single scientific paper arguing that all non-coding DNA is junk. I challenge Philip Ball to find a single molecular biology textbook written before 1990 that fails to discuss regulation, non-coding genes, and other non-coding functional elements in the human genome.
The truth is that the molecular biology experts concluded in the 1970s that we had about 30,000 genes and that 90% of our genome is junk and 10% is functional. That 10% consisted of about 2% coding DNA (now thought to be only 1%) and 8% functional non-coding DNA. So the "conventional narrative" was that there was a lot more functional non-coding DNA than coding DNA.
The human genome is full of genes for regulatory RNAs.
"Ball is one of the most meticulous, precise science writers out there. He is the antithesis of hypey, "dumb-it-down" reporting. He is MUCH more credible than you are, Laurence."
John Horgan July, 2024The title of the article I was discussing is "Revolutionary Genetics Research Shows RNA May Rule Our Genome." In that article Ball says that ENCODE was basically right and there are many more non-coding genes than protein-coding genes. I pointed out that Ball mentions some criticism of this idea but only to dismiss it. I said that "[Ball] wants you to believe that almost of all of those transcripts are functional—that's the revolution that he's promoting." Philip Ball objects to this statement ...
This too is sheer fabrication. I don’t say this in my article, nor in my book. Instead, I say pretty much what Larry seems to want me to say, but for some reason he will not admit it – which is that there is controversy about how many of the transcripts are functional."
Ball states that "ENCODE was basically right" when they claimed that 75% of our genome was transcribed and he goes on to say that ...
Dozens of other research groups, scoping out activity along the human genome, also have found that much of our DNA is churning out 'noncoding' RNA.
He says that ENCODE has identified 37,000 noncoding genes but there may be as many as 96,000. After making these definitive statements, he mentions that there are "still doubters" but then discuss why these discoveries are revolutionary. Later on he quotes John Mattick suspecting that there may be more that 500,000 non-coding genes.
Toward the end of the article, after discussing all kinds of functional RNAs, he brings up the Ponting and Haerty review where they say that most lncRNAs are just noise. He also mentions that the low copy number of non-coding RNAs raises questions about whether they are functional but immediately counters with the standard excuses from his allies.
Ball closes the article with ...
Gingeras says he is perplexed by ongoing claims that ncRNAs are merely noise or junk, as evidence is mounting that they do many things. "It is puzzling why there is such an effort to persuade colleagues to move from a sense of interest and curiosity in the ncRNA field to a more dubious and critical one," he says.
Perhaps the arguments are so intense because they undercut the way we think our biology works. Ever since the epochal discovery about DNA's double helix and how it encodes information, the bedrock idea of molecular biology has been that there are precisely encoded instructions that program specific molecules for particular tasks. But ncRNAs seem to point to a fuzzier, more collective, logic to life. It is a logic that is harder to discern and harder to understand. ut if scientists can learn to live with the fuzziness, this view of life may turn out to be more complete.
What's remarkable about the quote from a leading ENCODE worker (Gingeras) is that he is "puzzled" by scientists who are dubious and critical about claims in the ncRNA field. Isn't that what good scientists are supposed to do? Isn't that exactly what we did when we successfully challenged the dubious claims about junk DNA made in 2012?
There is no doubt in my mind that Philip Ball has fallen hook-line-and-sinker for the ENCODE claims that our genome is buzzing with non-coding genes. He only brings up the counter-arguments to dismiss them and pretend that he is being fair. Nobody who was truly skeptical about the function of transcripts would write an article with the title, "Revolutionary Genetics Research Shows RNA May Rule Our Genome."
However, as Ball points out in other comments, he does have a sentence in his book where he mentions that perhaps only 30% of the genome is functional. He says in the comment that what he believes is that the amount of functional DNA lies somewhere between 10% and 30%. That's not something that he mentions in the Scientific American article but, if he's being honest, it does mean that I was unfair when I said he believes that "almost of all of those transcripts are functional" but I only know that from what he now says, not from the published article.
If I were to take Philip Ball at his word—as expressed in the comment—then he must believe that most of the ENCODE transcripts are junk RNA. That's not a belief that you get from reading his published work.2 Furthermore, if I were to take him at his word, then he must believe that there are some reasonable criteria that must be applied to a transcript in order to decide whether it has a biologically relevant function. So, when he says that ENCODE identified 37,600 non-coding genes he must have these criteria in mind but he doesn't express any serious skepticism about that number. We all know that there's no solid evidence that such a large number of transcripts are functional but that doesn't bother Philip Ball. He thinks we are in the middle of an RNA revolution.
1. In commenting to my previous post, Ball says he believes that somewhere between 70% and 90% of our genome is junk but he doesn't say this in the Scientific American article. Instead, he says that scientists were surprised to learn that 75% of the human genome is transcribed implying that there's a lot of function. He goes on the say that "ENCODE was basically right." But what the ENCODE publicity campaign actually said was that junk DNA is dead and there's practically no junk DNA. If Ball really believes that up to 90% of the genome is junk then to me this means that ENCODE was spectacularly wrong not "basically right."
2. Ball says that 75% of the genome is transcribed. If Ball believes that as little as 10% may be functional then he must believe that less than 10% is transcribed to produce functional RNAs since he has to allow for regulatory sequences and other functional DNA elements. Let's say that 8% is a reasonable number. Ball seems to be willing to admit that 67% of the genome might be transcribed to produce junk RNA.
Thursday, March 21, 2024
Science misinformation is being spread in the lecture halls of top universities
Should universities remove online courses that contain incorrect or misleading information?
There are lots of scientific controversies where different scientists have conflicting views. Eventually these controversies will be solved by normal scientific means involving evidence and logic but for the time being there isn't enough data to settle a genuine scientific controversy. Many of us are interested in these controversies and some of us have chosen to invest time and effort into defending one side or the other.
But there's a dark side of science that infects these debates—false or misleading information used to support one side of a legitimate controversy. To give just one example, I'm frustrated at the constant reference to junk DNA being defined as non-coding DNA. Many scientists believe that this was the way junk DNA was defined by its earliest proponents and then they go on to say that the recent discovery of functional non-coding DNA refutes junk.
I don't know where this idea came from because there's nothing in the scientific literature from 50 years ago to support such a ridiculous claim. It must be coming from somewhere since the idea is so widespread.
Where does misinformation come from and how is it spread?
Wednesday, February 07, 2024
Philip Ball's new book: "How Life Works"
Monday, November 20, 2023
Two Heidelberg graduate students reject junk DNA
Science in School is a magazine for European science teachers. Two graduate students1 have just published an article in the November issue: Not junk after all: the importance of non-coding RNAs.
Note: The article has been edited to remove some of the references to junk DNA and the editor has added the following disclaimer to the end of the article: Editor’s note: Some parts of the introduction and conclusion were rephrased to avoid any misunderstanding concerning the nature of ‘junk DNA’, which is not the focus of this article. Here's a link to the revised article: Not junk after all: the importance of non-coding RNAs. More changes are expected.
Not junk after all: the importance of non-coding RNAs
Originally assumed to be useless ‘junk DNA’, sections of the genome that don’t encode proteins have been revealed as a source of many important non-coding RNA structures.
The central dogma of molecular biology is that DNA is used as a template to create messenger RNA (mRNA), which in turn is translated into proteins that build the tissues in our bodies and carry out the main functions of our cells and organs. In other words, DNA → mRNA → proteins. Interestingly, though, only 2% of the DNA in our whole genome codes for proteins! So, what does the other 98% of the human genome do? In the mid-1900s, it was widely believed that a great part of our genome was useless, repetitive ‘junk DNA’. However, this belief goes against the evolution theory, which suggests that useless sequences would be eliminated from the genome since their maintenance requires energy. In the late 20th century and the early 21st century, this junk DNA has been shown to not only contain important regulatory elements for transcription, but also sequences that encode various non-coding RNAs that have functions in many cellular mechanisms.
I just finshed a podcast interview with Kat Arney and one of the questions she asked was what is the most important thing I'd like scientists to know about this topic. I picked evolution—I'd like modern researchers to understand that there's more to evolution than natural selection. You can see the problem in this example where two students who are working toward a Ph.D. at a top lab in Europe think that junk DNA "goes against the evolution theory."
That's sad. It's also sad that these two students think that 98% of our genome might be devoted to regulation and non-coding genes.
We need to focus on educating the next generation of scientists and that starts with educating science teachers. This is not the way to do it.
Here's the contact information for Science in School. I've written the editor at editor@scienceinschool.org. Please send a message if you are as concerned about the spread of scientific misinformation as I am.
Zuzana Koskova at the European Molecular Biology Laboratory in Heidelberg (Germany) and Miguel Hernandez at the University Hospital, Heidelberg. I tried sending an email message to Zuzana Koskova but got no reply. I was unable to find contact information for Miguel Hernandez.
Monday, September 04, 2023
John Mattick's paradigm shaft
Paradigm shifts are rare but paradigm shafts are common. A paradigm shaft is when a scientist describes a false paradigm that supposedly ruled in the past then shows how their own work overthrows that old (false) paradigm.1 In many cases, the data that presumably revolutionizes the field is somewhat exaggerated.
John Mattick's view of eukaryotic RNAs is a classic example of a paradigm shaft. At various times in the past he has declared that molecular biology used to be dominated by the Central Dogma, which, according to him, supported the concept that the only function of DNA was to produce proteins (Mattick, 2003; Morris and Mattick, 2014). More recently, he has backed off this claim a little bit by conceding that Crick allowed for functional RNAs but that proteins were the only molecules that could be involved in regulation. The essence of Mattick's argument is that past researchers were constrained by adherance to the paradigm that the only important functional molecules were proteins and RNA served only an intermediate role in protein synsthesis.
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].
Monday, May 15, 2023
Chapter 8: Noncoding Genes and Junk RNA
I think there are no more than 5,000 noncoding genes but many scientists claim that there are tens of thousands of newly discovered noncoding genes. I describe the known noncoding genes (less than 1000) and explain why many of the transcripts detected are just junk RNA produced by spurious transcription. The presence of abundant noncoding genes will not solve the Deflated Ego Problem.
This chapter covers the misconceptions about the Central Dogma and how they are incorrectly used to try and discredit junk DNA. The views of John Mattick are explained and refuted. I end the chapter with a plea to adopt a worldview that can accommodate messy biochemistry and a sloppy genome that's full of junk DNA.
Click on this link to see more.
Chapter 8: NoncodingGenes and Junk RNASaturday, March 25, 2023
ChatGPT lies about junk DNA
I asked ChatGPT some questions about junk DNA and it made up a Francis Crick quotation and misrepresented the view of Susumu Ohno.
We have finally restored the Junk DNA article on Wikipedia. (It was deleted about ten years ago when Wikipedians decided that junk DNA doesn't exist.) One of the issues on Wikipedia is how to deal with misconceptions and misunderstandings while staying within the boundaries of Wikipedia culture. Wikipedians have an aversion to anything that looks like editorializing so you can't just say something like, "Nobody ever said that all non-coding DNA was junk." Instead, you have to find a credible reference to someone else who said that.
I've been trying to figure out how far the misunderstandings of junk DNA have spread so I asked ChatGPt (from OpenAI) again.
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?
Saturday, January 28, 2023
ChatGPT won't pass my exams!
Here are a few questions for ChatGPT and its answers. The AI program takes the most common information on the web and spews it back at you. It cannot tell which information is correct or which information is more accurate.
It's easy to recognize that these answers were written by something that's not very good at critical thinking. I agree with other professors that they mimic typical undergraduate answers but I disagree that these answers would get them a passing grade.
ChatGPT shares one very important feature that's common in undergraduate answers to essay questions: it gives you lots of unecessary information that's not directly relevant to the question.
It's important to note that (lol) these ChatGPT answers share another important feature with many of the answers on my exams: they look very much like BS!
Sunday, December 18, 2022
Protein concentrations in E. coli are mostly controlled at the level of transcription initiation
The most important step in the regulation of protein-coding genes in E. coli is the rate of binding of RNA polymerase to the promoter region.
A group of scientists at the University of California at San Diego and their European collaborators looked at the concentrations of proteins and mRNAs of about 2000 genes in E. coli. They catalogued these concentrations under several different growth conditions in order to determine whether the level of protein being expressed from each of these genes correlated with transcription rate, translation rate, mRNA stability or other levels of gene expression.
The paper is very difficult to understand because the authors are primarily interested in developing mathematical formulae to describe their results. They expect you to understand equations like,
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, October 13, 2022
Macroevolution
(This is a copy of an essay that I published in 2006. I made some minor revisions to remove outdated context.)
Overheard at breakfast on the final day of a recent scientific meeting: "Do you believe in macroevolution?" Came the rely: "Well, it depends on how you define it."
Roger Lewin (1980)There is no difference between micro- and macroevolution except that genes between species usually diverge, while genes within species usually combine. The same processes that cause within-species evolution are responsible for above-species evolution.
John Wilkins
The minimalist definition of evolution is a change in the hereditary characteristics of a population over the course of many generations. This is a definition that helps us distinguish between changes that are not evolution and changes that meet the minimum criteria. The definition comes from the field of population genetics developed in the early part of the last century. The modern theory of evolution owes much to population genetics and our understanding of how genes work. But is that all there is to evolution?
The central question of the Chicago conference was whether the mechanisms underlying microevolution can be extrapolated to explain the phenomena of macroevolution. At the risk of doing violence to the positions of some of the people at the meeting, the answer can be given as a clear, No.Roger Lewin (1980)
No. There's also common descent—the idea that all life has evolved from primitive species over billions of years. Common descent is about the history of life. In this essay I'll describe the main features of how life evolved but keep in mind that this history is a unique event that is accidental, contingent, quirky, and unpredictable. I'll try and point out the most important controversies about common descent.
The complete modern theory of evolution encompasses much more than changes in the genetics of a population. It includes ideas about the causes of speciation, long-term trends, and mass extinctions. This is the domain of macroevolution—loosely defined as evolution above the species level. The kind of evolution that focuses on genes in a population is usually called microevolution.
As a biochemist and a molecular biologist, I tend to view evolution from a molecular perspective. My main interest is molecular evolution and the analysis of sequences of proteins and nucleic acids. One of the goals in writing this essay is to explain this aspect of evolution to the best of my limited ability. However, another important goal is to show how molecular evolution integrates into the bigger picture of evolution as described by all other evolutionary biologists, including paleontologists. When dealing with macroevolution this is very much a learning experience for me since I'm not an expert. Please bear with me while we explore these ideas.
It's difficult to define macroevolution because it's a field of study and not a process. Mark Ridley has one of the best definitions I've seen ...
Macroevolution means evolution on the grand scale, and it is mainly studied in the fossil record. It is contrasted with microevolution, the study of evolution over short time periods., such as that of a human lifetime or less. Microevolution therefore refers to changes in gene frequency within a population .... Macroevolutionary events are more likely to take millions, probably tens of millions of years. Macroevolution refers to things like the trends in horse evolution described by Simpson, and occurring over tens of millions of years, or the origin of major groups, or mass extinctions, or the Cambrian explosion described by Conway Morris. Speciation is the traditional dividing line between micro- and macroevolution.
Mark Ridley (1997) p. 227
When we talk about macroevolution we're talking about studies of the history of life on Earth. This takes in all the events that affect the actual historical lineages leading up to today's species. Jeffrey S. Levinton makes this point in his description of the field of macroevolution and it's worth quoting what he says in his book Genetics, Paleontology, and Macroevolution.
Macroevolution must be a field that embraces the ecological theater, including the range of time scales of the ecologist, to the sweeping historical changes available only to paleontological study. It must include the peculiarities of history, which must have had singular effects on the directions that the composition of the world's biota took (e.g., the splitting of continents, the establishment of land and oceanic isthmuses). It must take the entire network of phylogenetic relationships and impose a framework of genetic relationships and appearances of character changes. Then the nature of evolutionary directions and the qualitative transformation of ancestor to descendant over major taxonomic distances must be explained.
Jeffrey S. Levinton (2001) p.6
Levinton then goes on to draw a parallel between microevolution and macroevolution on the one hand, and physics and astronomy on the other. He points out that the structure and history of the known universe has to be consistent with modern physics, but that's not sufficient. He gives the big bang as an example of a cosmological hypothesis that doesn't derive directly from fundamental physics. I think this analogy is insightful. Astronomers study the life and death of stars and the interactions of galaxies. Some of them are interested in the formation of planetary systems, especially the unique origin of our own solar system. Explanations of these "macro" phenomena depend on the correctness of the underlying "micro" physics phenomena (e.g., gravity, relativity) but there's more to the field of astronomy than that.
Levinton continues ....
In conclusion, then, macroevolutionary processes are underlain by microevolutionary phenomena and are compatible with microevolutionary theories, but macroevolutionary studies require the formulation of autonomous hypotheses and models (which must be tested using macroevolutionary evidence). In this (epistemologically) very important sense, macroevolution is decoupled from microevolution: macroevolution is an autonomous field of evolutionary study.Does the evolutionary biologist differ very much from this scheme of inference? A set of organisms exists today in a partially measurable state of spatial, morphological, and chemical relationships. We have a set of physical and biological laws that might be used to construct predictions about the outcome of the evolutionary process. But, as we all know, we are not very successful, except at solving problems at small scales. We have plausible explanations for the reason why moths living in industrialized areas are rich in dark pigment, but we don't know whether or why life arose more than once or why some groups became extinct (e.g., the dinosaurs) whereas others managed to survive (e.g., horseshoe crabs). Either our laws are inadequate and we have not described the available evidence properly or no such laws can be devised to predict uniquely what should have happened in the history of life. For better or worse, macroevolutionary biology is as much historical as is astronomy, perhaps with looser laws and more diverse objectives....
Indeed, the most profound problem in the study of evolution is to understand how poorly repeatable historical events (e.g., the trapping of an endemic radiation in a lake that dries up) can be distinguished from lawlike repeatable processes. A law that states 'an endemic radiation will become extinct if its structural habitat disappears' has no force because it maps to the singularity of a historical event.
Jeffrey S. Levinton (2001) p.6-7
Francisco J. Ayala (1983)
I think it's important to appreciate what macroevolutionary biologists are saying. Most of these scientists are paleontologists and they think of their area of study as an interdisciplinary field that combines geology and biology. According to them, there's an important difference between evolutionary theory and the real history of life. The actual history has to be consistent with modern evolutionary theory (it is) but the unique sequence of historical events doesn't follow directly from application of evolutionary theory. Biological mechanisms such as natural selection and random genetic drift are part of a much larger picture that includes moving continents, asteroid impacts, ice ages, contingency, etc. The field of macroevolution addresses these big picture issues.
Clearly, there are some evolutionary biologists who are only interested in macroevolution. They don't care about microevolution. This is perfectly understandable since they are usually looking at events that take place on a scale of millions of years. They want to understand why some species survive while others perish and why there are some long-term trends in the history of life. (Examples of such trends are the loss of toes during the evolution of horses, the development of elaborate flowers during the evolution of vascular plants, and the tendency of diverse species, such as the marsupial Tasmanian wolf and the common placental wolf, to converge on a similar body plan.)
Nobody denies that macroevolutionary processes involve the fundamental mechanisms of natural selection and random genetic drift, but these microevolutionary processes are not sufficient, by themselves, to explain the history of life. That's why, in the domain of macroevolution, we encounter theories about species sorting and tracking, species selection, and punctuated equilibria.
Micro- and macroevolution are thus different levels of analysis of the same phenomenon: evolution. Macroevolution cannot solely be reduced to microevolution because it encompasses so many other phenomena: adaptive radiation, for example, cannot be reduced only to natural selection, though natural selection helps bring it about.Eugenie C. Scott (2004)
As I mentioned earlier, most of macroevolutionary theory is intimately connected with the observed fossil record and, in this sense, it is much more historical than population genetics and evolution within a species. Macroevolution, as a field of study, is the turf of paleontologists and much of the debate about a higher level of evolution (above species and populations) is motivated by the desire of paleontologists to be accepted at the high table of evolutionary theory. It's worth recalling that during the last part of the twentieth century evolutionary theorizing was dominated by population geneticists. Their perspective was described by John Maynard Smith, "... the attitude of population geneticists to any paleontologist rash enough to offer a contribution to evolutionary theory has been to tell him to go away and find another fossil, and not to bother the grownups." (Maynard Smith, 1984)
The distinction between microevolution and macroevolution is often exaggerated, especially by the anti-science crowd. Creationists have gleefully exploited the distinction in order to legitimate their position in the light of clear and obvious examples of evolution that they can't ignore. They claim they can accept microevolution, but they reject macroevolution.
In the real world—the one inhabited by rational human beings—the difference between macroevolution and microevolution is basically a difference in emphasis and level. Some evolutionary biologists are interested in species, trends, and the big picture of evolution, while others are more interested in the mechanics of the underlying mechanisms.
Speciation is critical to conserving the results of both natural selection and genetic drift. Speciation is obviously central to the fate of genetic variation, and a major shaper of patterns of evolutionary change through evolutionary time. It is as if Darwinians—neo- and ulra- most certainly included—care only for the process generating change, and not about its ultimate fate in geological time.Niles Eldredge (1995)
The Creationists would have us believe there is some magical barrier separating selection and drift within a species from the evolution of new species and new characteristics. Not only is this imagined barrier invisible to most scientists but, in addition, there is abundant evidence that no such barrier exists. We have numerous examples that show how diverse species are connected by a long series of genetic changes. This is why many scientists claim that macroevoluton is just lots of microevolution over a long period of time.
But wait a minute. I just said that many scientists think of macroevolution as simply a scaled-up version of microevolution, but a few paragraphs ago I said there's more to the theory of evolution than just changes in the frequency of alleles within a population. Don't these statements conflict? Yes, they do ... and therein lies a problem.
When the principle tenets of the Modern Synthesis were being worked out in the 1940's, one of the fundamental conclusions was that macroevolution could be explained by changes in the frequency of alleles within a population due, mostly, to natural selection. This gave rise to the commonly accepted notion that macroevolution is just a lot of microevolution. Let's refer to this as the sufficiency of microevolution argument.
At the time of the synthesis, there were several other explanations that attempted to decouple macroevolution from microevolution. One of these was saltation, or the idea that macroevolution was driven by large-scale mutations (macromutations) leading to the formation of new species. This is the famous "hopeful monster" theory of Goldschmidt. Another decoupling hypothesis was called orthogenesis, or the idea that there is some intrinsic driving force that directs evolution along certain pathways. Some macroevolutionary trends, such as the increase in the size of horses, were thought to be the result of this intrinsic force.
Both of these ideas about macroevolutionary change (saltation and orthogensis) had support from a number of evolutionary biologists. Both were strongly opposed by the group of scientists that produced the Modern Synthesis. One of the key players was the paleontologist George Gaylord Simpson whose books Tempo and Mode in Evolution (1944) and The Major Features of Evolution (1953) attempted to combine paleontology and population genetics. "Tempo" is often praised by evolutionary biologists and many of our classic examples of evolution, such as the bushiness of the horse tree, come from that book. It's influence on paleontologists was profound because it upset the traditional view that macroevolution and the newfangled genetics had nothing in common.
Just as mutation and drift introduce a strong random component into the process of adaptation, mass extinctions introduce chance into the process of diversification. This is because mass extinctions are a sampling process analogous to genetic drift. Instead of sampling allele frequencies, mass extinctions samples species and lineages. ... The punchline? Chance plays a large role in the processes responsible for adaptation and diversity.Freeman and Herron (1998)
We see, in context, that the blurring of the distinction between macroevolution and microevolution was part of a counter-attack on the now discredited ideas of saltation and orthogenesis. As usual, when pressing the attack against objectionable ideas, there's a tendency to overrun the objective and inflict collateral damage. In this case, the attack on orthogenesis and the old version of saltation was justified since neither of these ideas offer viable alternatives to natural selection and drift as mechanisms of evolution. Unfortunately, Simpson's attack was so successful that a generation of scientists grew up thinking that macroevolution could be entirely explained by microevolutionary processes. That's why we still see this position being advocated today and that's why many biology textbooks promote the sufficiency of microevolution argument. Gould argues—successfully, in my opinion—that the sufficiency of microevolution became dogma during the hardening of the synthesis in the 1950-'s and 1960's. It was part of an emphasis on the individual as the only real unit of selection.
However, from the beginning of the Modern Synthesis there were other evolutionary biologists who wanted to decouple macroevolution and microevolution—not because they believed in the false doctrines of saltation and orthogenesis, but because they knew of higher level processes that went beyond microevolution. One of these was Ernst Mayr. In his essay "Does Microevolution Explain Macroevolution," Mayr says ...
Among all the claims made during the evolutionary synthesis, perhaps the one that found least acceptance was the assertion that all phenomena of macroevolution can be ‘reduced to,' that is, explained by, microevolutionary genetic processes. Not surprisingly, this claim was usually supported by geneticists but was widely rejected by the very biologists who dealt with macroevolution, the morphologists and paleontologists. Many of them insisted that there is more or less complete discontinuity between the processes at the two levels—that what happens at the species level is entirely different from what happens at the level of the higher categories. Now, 50 years later the controversy remains undecided.
Ernst Mayr (1988) p.402
Mayr goes on to make several points about the difference between macroevolution and microevolution. In particular, he emphasizes that macroevolution is concerned with phenotypes and not genotypes, "In this respect, indeed, macroevolution as a field of study is completely decoupled from microevolution." (ibid p. 403). This statement reiterates an important point, namely that macroevolution is a "field of study" and, as such, its focus differs from that of other fields of study such as molecular evolution.
If you think of macroevolution as a field of study rather than a process, then it doesn't make much sense to say that macroevolution can be explained by the process of changing alleles within a population. This would be like saying the entire field of paleontology can be explained by microevolution. This is the point about the meaning of the term "macroevolution" that is so often missed by those who dismiss it as just a bunch of microevolution.
The orthodox believers in the hardened synthesis feel threatened by macroevolution since it implies a kind of evolution that goes beyond the natural selection of individuals within a population. The extreme version of this view is called adaptationism and the believers are called Ultra-Darwinians by their critics. This isn't the place to debate adaptationism: for now, let's just assume that the sufficiency of microevolution argument is related to the pluralist-adaptationist controversy and see how our concept of macroevolution as a field of study relates to the issue. Niles Eldredge describes it like this ...
The very term macroevolution is enough to make an ultra-Darwinian snarl. Macroevolution is counterpoised with microevolution—generation by generation selection- mediated change in gene frequencies within populations. The debate is over the question, Are conventional Darwinian microevolutionary processes sufficient to explain the entire history of life? To ultra-Darwinians, the very term macroevolution suggests that the answer is automatically no. To them, macroevolution implies the action of processes—even genetic processes—that are as yet unknown but must be imagined to yield a satisfactory explanation of the history of life.
But macroevolution need not carry such heavy conceptual baggage. In its most basic usage, it simply means evolution on a large-scale. In particular, to some biologists, it suggests the origin of major groups - such as the origin and radiation of mammals, or the derivation of whales and bats from terrestrial mammalian ancestors. Such sorts of events may or may not demand additional theory for their explanation. Traditional Darwinian explanation, of course, insists not.
Niles Eldredge (1995) p. 126-127
Eldredge sees macroevolution as a field of study that's mostly concerned with evolution on a large scale. Since he's a paleontologist, it's likely that, for him, macroevolution is the study of evolution based on the fossil record. Eldredge is quite comfortable with the idea that one of the underlying causes of evolution can be natural selection—this includes many changes seen over the course of millions of years. In other words, there is no conflict between microevolution and macroevolution in the sense that microevolution stops and is replaced by macroevolution above the level of species. But there is a conflict in the sense that Eldredge, and many other evolutionary biologists, do not buy the sufficiency of microevolution argument. They believe there are additional theories, and mechanisms, needed to explain macroevolution. Gould says it best ....
We do not advance some special theory for long times and large transitions, fundamentally opposed to the processes of microevolution. Rather, we maintain that nature is organized hierarchically and that no smooth continuum leads across levels. We may attain a unified theory of process, but the processes work differently at different levels and we cannot extrapolate from one level to encompass all events at the next. I believe, in fact, that ... speciation by splitting guarantees that macroevolution must be studied at its own level. ... [S]election among species—not an extrapolation of changes in gene frequencies within populations—may be the motor of macroevolutionary trends. If macroevolution is, as I believe, mainly a story of the differential success of certain kinds of species and, if most species change little in the phyletic mode during the course of their existence, then microevolutionary change within populations is not the stuff (by extrapolation) of major transformations.
Stephen Jay Gould (1980b) p. 170
Naturalists such as Ernst Mayr and paleontologists such as Gould and Eldredge have all argued convincingly that speciation is an important part of evolution. Since speciation is not a direct consequence of changes in the frequencies of alleles in a population, it follows that microevolution is not sufficient to explain all of evolution. Gould and Eldredge (and others) go even further to argue that there are processes such as species sorting that can only take place above the species level. This means there are evolutionary theories that only apply in the domain of macroevolution.
The idea that there's much more to evolution than genes and population genetics was a favorite theme of Stephen Jay Gould. He advocated a pluralist, hierarchical approach to evolution and his last book The Structure of Evolutionary Theory emphasized macroevolutionary theory—although he often avoided using this term. The Structure of Evolutionary Theory is a huge book that has become required reading for anyone interested in evolution. Remarkably, there's hardly anything in the book about population genetics, molecular evolution, and microevolution as popularly defined. What better way of illustrating that macroevolution must be taken seriously!
Macroevolutionary theory tries to identify patterns and trends that help us understand the big picture. In some cases, the macroevolution biologists have recognized generalities (theories & hypotheses) that only apply to higher level processes. Punctuated equilibria and species sorting are examples of such higher level phenomena. The possible repeatedness of mass extinctions might be another.
Remember that macroevolution should not be contrasted with microevolution because macroevolution deals with history. Microevolution and macroevolution are not competing explanations of the history of life any more than astronomy and physics compete for the correct explanation of the history of the known universe. Both types of explanation are required.
I think species sorting is the easiest higher level phenomena to describe. It illustrates a mechanism that is clearly distinct from changes in the frequencies of alleles within a population. In this sense, it will help explain why microevolution isn't a sufficient explanation for the evolution of life. Of course, one needs to emphasize that macroevolution must be consistent with microevolution.
I have championed contingency, and will continue to do so, because its large realm and legitimate claims have been so poorly attended by evolutionary scientists who cannot discern the beat of this different drummer while their brains and ears remain tuned to only the sounds of general theory.Stephen Jay Gould (2002)
If we could track a single lineage through time, say from a single-cell protist to Homo sapiens, then we would see a long series of mutations and fixations as each ancestral population evolved. It might look as though the entire history could be accounted for by microevolutionary processes. This is an illusion because the track of the single lineage ignores all of the branching and all of the other species that lived and died along the way. That track would not explain why Neanderthals became extinct and Cro-Magnon survived. It would not explain why modern humans arose in Africa. It would not tell us why placental mammals became more successful than the dinosaurs. It would not explain why humans don't have wings and can't breathe underwater. It doesn't tell us whether replaying the tape of life will automatically lead to humans. All of those things are part of the domain of macroevolution and microevolution isn't sufficient to help us understand them.
Tuesday, June 14, 2022
Distrust simplicity (and turn off your irony meters)
I just stumbled upon an opinion piece published in EMBO Reports on May 22, 2022. The author is Frank Gannon who is identified as the former Director of the QIMR Berghofer Medical Research Institute in Brisbane, Australia and the title of the article is "Seek simplicity and distrust it."
I'm about to quote some excerpts from the article but before doing so I need to warn you to run off your irony meters—even if you have the latest version with the most recent software updates.
Gannon's main point is that scientists should seek simple explanations but they must be willing to abandon them when better data comes along. He gives us some examples.
However, it seems that there is a collective amnesia among scientists such that we forget to distrust the simplicity that we pursue on our path to insight. The central dogma of molecular biology—that information flows unidirectionally from DNA to RNA to protein—was overturned, at least in part, with the discovery that this linear cascade could be reversed by reverse transcription.
Really? The Central Dogma of Molecular Biology was overturned, "at least in part," by reverse transcriptase? (It wasn't.) If you are going to write about a topic like this then you'd better make sure you know what you're talking about.
The great quote from Jacques Monod “What is true for E. coli is true for the elephant”, held valid only until the discovery of introns in eukaryotes. As I was close to the earliest data that pointed to the existence of split genes, I am well aware of the incredulity of biologists when they realised that genetic material did not have the same simple design irrespective of the organism.
Monod's statement was never supposed to be taken as literally as that.1 He was referring to the unity of biochemistry (Friedman, 2004). This is clear from what he says in Chance and Necessity, "Today we know that from the bacterium to man the chemical machinery is essentially the same, in both its structure and functioning." He meant that all species have DNA, RNA, and protein and that these molecules carry out the same roles in humans as they do in bacteria. The essence of this simple observation is as true today as it was 50 years ago.
The death of “Junk DNA”—a term, coined in 1972 by Susumu Ohno for the non-coding parts of the genome—has been more gradual. The perception that exons are the only useful part of the genome has been proven wrong with the discoveries of noncoding RNA, the controlling roles of intra-genomic areas, the essential interactions between distant genomic regions and peptides encoded by short open frame regions.
Did you turn off your irony meter? Don't say I didn't warn you. Jacques Monod (and Susumu Ohno) would be surprised to learn that in 1972 they knew nothing about noncoding genes and regulatory sequences.
More seriously, how did we ever get to the stage where a prominent scientist who frequently publishes opinion pieces in EMBO Reports could be so ignorant of the junk DNA controversy after all that's been written about it in the past ten years?
1. Besides, introns exist in bacteria.
Friedman, H.C. (2004) From Butyribacterium to E. coli: An Essay on Unity in Biochemistry. Perspectives in Biology and Medicine 47:47-66. [doi: 10.1353/pbm.2004.0007]
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