How Does Something Get into a Textbook?

A recent paper in Molecular Cell involved the study of nucleosome assembly in vitro (Torigoe et al. 2011). The authors were looking for intermediate stages in the assembly of nucleosome after DNA replication. Here's the abstract of their paper ...

Chromatin assembly involves the combined action of histone chaperones and ATP-dependent motor proteins. Here, we investigate the mechanism of nucleosome assembly with a purified chromatin assembly system containing the histone chaperone NAP1 and the ATP-dependent motor protein ACF. These studies revealed the rapid formation of a stable nonnucleosomal histone-DNA intermediate that is converted into canonical nucleosomes by ACF. The histone-DNA intermediate does not supercoil DNA like a canonical nucleosome, but has a nucleosome-like appearance by atomic force microscopy. This intermediate contains all four core histones, lacks NAP1, and is formed by the initial deposition of histones H3-H4. Conversion of the intermediate into histone H1-containing chromatin results in increased resistance to micrococcal nuclease digestion. These findings suggest that the histone-DNA intermediate corresponds to nascent nucleosome-like structures, such as those observed at DNA replication forks. Related complexes might be formed during other chromatin-directed processes such as transcription, DNA repair, and histone exchange.

Interesting but hardly Earth-shattering. More work needs to be done to confirm this result and see if it's significant in vivo. At least that's what you would think if you just looked at the paper.

You get a very different perspective if you read the press release from the University of California at San Diego: Biologists' Discovery May Force Revision of Biology Textbooks: Novel Chromatin Particle Halfway Between DNA and a Nucleosome.¹

Basic biology textbooks may need a bit of revising now that biologists at UC San Diego have discovered a never-before-noticed component of our basic genetic material.

According to the textbooks, chromatin, the natural state of DNA in the cell, is made up of nucleosomes. And nucleosomes are the basic repeating unit of chromatin.

That's correct. All the textbooks have a diagram similar to the one shown here from my textbook. It shows the organization of nucleosome core particles and the completed nucleosome on DNA.

What the new result shows is that there's an intermediate stage where the core particle is bound to DNA but the DNA isn't wrapped around the core particle. That's not a big surprise and it's not going to make it into most textbooks, even if it's true.

"This novel particle was found as a precursor to a nucleosome," said James Kadonaga, a professor of biology at UC San Diego who headed the research team and calls the particle a "pre-nucleosome." "These findings suggest that it is necessary to reconsider what chromatin is. The pre-nucleosome is likely to be an important player in how our genetic material is duplicated and used."

The biologists say that while the pre-nucleosome may look something like a nucleosome under the microscope, biochemical tests have shown that it is in reality halfway between DNA and a nucleosome.

These pre-nucleosomes, the researchers say, are converted into nucleosomes by a motor protein that uses the energy molecule ATP.

"The discovery of pre-nucleosomes suggests that much of chromatin, which has been generally presumed to consist only of nucleosomes, may be a mixture of nucleosomes and pre-nucleosomes," said Kadonaga. "So, this discovery may be the beginning of a revolution in our understanding of what chromatin is."

This is mostly hype and none of this speculation is found in the actual paper. Unfortunately, this sort of press release has become the norm and that's got to stop.

This work isn't even close to making into the textbooks for a number of reasons. The most obvious is that it needs to be confirmed. Textbook writers do not immediately put new findings into their books because we've been burned too many times. But there's another reason why this ain't gonna make it—it's not important enough.

Textbooks are not encyclopedias. They will only contain information that undergraduates need to know in order to understand the basic concepts and principles in the field. I know that every scientist thinks his or her most recent discovery is Nobel Prize work and I'm sure they would like every biochemistry undergraduate to know about it. At some point a textbook author has to decide what's really important and, unfortunately, those choices mean that 99.99% of everything that's published in a given year doesn't make the cut.

It can't be any other way.

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1. It even seemed important enough for Richard Dawkins.net: Biologists' Discovery May Force Revision of Biology Textbooks: Novel Chromatin Particle Halfway Between DNA and a Nucleosome.

How to Convince an Atheist to Become an IDiot

You all remember GilDodgen, right? He's one of the IDiots who post regularly on Uncommon Descent. Nothing that he says about Intelligent Design Creationism is unusual but he does have one characteristic that appeasr to set him apart. Here's how he describes himself [ID and Prager University].

As many UD readers know, I was once a Richard Dawkins-style atheist. I was not just an ordinary, garden-variety atheist, but a really obnoxious, nasty, self-aggrandizing, pathetically prideful atheist like Dawkins. I prided myself in using my intellectual capacities in an attempt to destroy any belief that materialism cannot explain everything.

Can you believe it? He used to be just like Richard Dawkins: obnoxious, nasty, self-aggrandizing, and prideful. (GilDodgen is still all of those things but now he's an IDiot.)

What an amazing transformation! I bet you're wondering, just like me, how the other IDiots managed to convert him.

Well wait no longer 'cause GilDodgen lets us in on the secret.

What a fool I was. The story of my conversion is available, but the most salient point concerning ID is that my interest and expertise in basic science, engineering, and especially highly sophisticated computational algorithms, led me to recognize the inherent design in living systems and the transparent desperation of ID opponents to explain away the obvious.

A major influence in my journey over the years has been Dennis Prager. I first started listening to him on the radio more than 20 years ago. His intelligence, eloquence, and articulation about ultimate issues had a profound effect on me.

Prager is a Jew, not a mindless evangelical Christian.

For those who are interested, check out Prager University, especially here and here.

Did you resist clicking on the links to Prager University? No, neither did I. There was just too much potential for a good laugh.

Let's look at the first of these major influences on the life of an atheist. We'll save the other one for later [Chitty Chitty Bang Bang Bang Bang].

The first thing you notice about the video is the title: The Most Important Verse in the Bible. That's exactly the sort of thing a nasty, materialist, atheist might be watching, right? Of course it is. That's exactly why we're all going to watch it!

The second thing you notice is the cation under the video.

No one, not even the most devoted atheist, denies that the Bible is the most influential book ever written. So, what is the most important verse in this most important book?

Now correct me if I'm wrong, but aren't there five billion non-Christians on this planet? Is it true that they can't think of a more influential book among all those that have ever been written?

Really? I didn't know that.

Before you watch the video, see if you can think of the most important verse in the Bible—assuming you have read it. Now watch the video and see how convincing it would be for a typical atheist.

WARNING: This video contain powerful theistic messages. Watching it might be hazardous to the rationality of atheists. Viewer discretion is advised.¹

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1. For the benefit of all non-Americans I should explain that this phrase is prominently displayed before every segment of a TV show (or movie) where you might catch a glimpse of an uncovered female breast or hear the word "shit." It's got to be one of the stupidest, meaningless, sentences every written.

Protein Folding, Chaperones, and IDiots

We know a lot about protein synthesis and structure. Proteins are made by the translation machinery (ribosomes + factors) as they copy the information in messenger RNA. When they are first synthesized, proteins can be visualized as random coils or even linear molecules consisting of a long string of amino acids joined end-to-end.

Eventually these newly synthesized molecules have to fold into a specific three-dimensional shape that's different for every protein. The diagram on the right illustrates this process for some hypothetical folding pathways.

To a first approximation, the final three-dimensional shape is determined by the amino acid sequence of the protein. The final shape represents the lowest free energy state of the folded protein and this can be represented as a free energy well. Left to their own devices, almost all proteins will eventually reach the bottom of the deepest well that represents the functional state of the protein. (There are exceptions to every rule in biology but this is a very good generality.)

There are many dips and troughs in the free energy landscape and sometimes proteins get trapped in a local minimum as shown by path B in the diagram on the left. If you wait long enough, the incorrectly folded protein will eventually get out of the local dip and fold into the correct shape. (This depends on an energy of activation.)

For the majority of proteins, this spontaneous folding is quite rapid. They reach the proper three-dimensional structure in seconds or minutes. For some proteins it may take much longer, especially if the free energy landscape is rugged and has many deep pits. When a spontaneous biochemical reaction is too slow to be useful it usually means that an enzyme is required to speed up the reaction. Recall that the role of enzymes is to accelerate reactions that occur spontaneoulsy—they do not create new reactions.

The "enzymes" that speed up protein folding are called molecular chaperones and they are among the most highly conserved enzymes in all of biology. As you might expect, these ancient enzymes are present in all species. There are several different kinds of chaperones but one of the most common is called HSP70 (heat shock protein of 70kDa). [Heat Shock and Molecular Chaperones] [The Evolution of the HSP70 Gene Family] [Gene HSPA5 Encodes BiP-a Molecular Chaperone].

HSP70 binds to hydrophobic regions of the folding protein preventing it from aggregating with other partially folded proteins and steering it toward the final three-dimensional structure. This greatly speeds up the folding pathway for those proteins that are otherwise slow to fold. Obviously there has been selection for rapidly folding proteins and/or selection for those that can be effectively assisted by chaperones. The genes for other proteins have not survived so what we see today are proteins that can fold rapidly with, or without, the assistance of chaperones.

Ulrich Hartl has just published a nice review of chaperones in Nature (Hartl et al. 2011). It didn't take long for the IDiots to comment. I spotted a posting on Uncommon Descent:Nature Review Article Yields Unpleasant Data For Darwinism, but that's just a link to another blog posting by a British IDiot named Antony Latham: New research on protein folding demonstrates intelligent design. Here's what Antony Latham has to say about chaperones.

The review in the journal Nature does not discuss the origins of these systems but we need to ask a question: how does all this fit with current evolutionary theory? One might think that such complex systems are confined to mammals or at least the higher orders of animals. This would be a mistake however, because chaperones and chaperonins are in bacteria and archaea also. Indeed it would seem that for any cell to function there needs to be not just proteins but, at the same time, these chaperone systems, which are absolutely essential for proper folding and maintenance of proteins. Without such systems, in place already, the cell will not function.

Now, as explained, these chaperone systems are themselves made of proteins which also require the assistance of chaperones to correctly fold and to maintain integrity once folded. Chaperones for chaperones in fact. The very simplest of cells that we know of have these systems in place.

Darwinian evolution requires step by step changes in molecular systems, with one step leading to another in a manner that is statistically reasonable to expect from selection of mutant strains. There is no Darwinian explanation however for the evolution of proteins which already have chaperone systems in place to ensure proper function.

This points very strongly to an intelligent origin of these ‘ingenious’ systems found in all of life.

All of the common chaperones fold spontaneously without the assistance of any other chaperones. The reason why they are called "heat shock" proteins is because their synthesis is induced when cells encounter high temperature or other conditions that may cause proteins to unfold or become unstable. These rescue chaperones are made in huge quantities under these conditions to help prevent the destruction of normal cellular proteins. If you understand this then you will understand that the chaperones themselves are capable of rapid spontaneous folding. Even if you didn't know the facts this would seem obvious.

In the beginning, you didn't need chaperones because every protein folded rapidly on its own. Some of these primitive proteins might have been a bit slow to fold so the evolution of the first chaperones was advantageous because it enhanced the rate of folding for these proteins. The chaperones weren't absolutely necessary for survival but they conferred a selective advantage on those cells that had them.

Once chaperones were present, new proteins could evolve that would otherwise have been too slow to fold in the absence of chaperones. Over time, cells accumulated more and more of these slowly folding proteins so that today no cell can survive without chaperones.

What we can't explain is why the IDiots keep putting their foots in their mouths.

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Hartl, F.U., Bracher, A., and Hayer-Hartl, M. (2011) Molecular chaperones in protein folding and proteostasis. Nature 475: 324–332. [Nature]

Ron Paul doesn't believe the theory, but what about the fact?

Here's a video where Ron Paul proclaims that he doesn't believe the Theory of Evolution. Unfortunately there's no followup question to find out whether he believes the facts of evolution. Why can Ron Paul make such a nonsensical statement and still be considered as someone who might be the "Leader of the Free World" (sic)? It's because of decades of brainwashing by creationists who blatantly ignore the science behind evolutionary biology and the distinction between fact and scientific theory.

I'm trying to understand the behavior of the creationists. It seems to me that there are only two possibilities; either they are completely stupid and ignorant or they are lying. There doesn't seem to be any other explanation. In the case of the most prominent creationists, I'm inclined to believe they are lying because I know for a fact they've read up on Evolution Is a Fact and a Theory.

This doesn't apply to Ron Paul, by the way. I don't think he's lying.

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[Hat Tip: Pharyngula: Ron Paul gets no respect. I think this is a video from 2008.

Nobel Prize in ... 2060

This is my granddaughter, Zoë, standing outside the Stockholm City Hall where they hold the Nobel Prize banquet every year on December 10th.

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Evolution of a New Enzyme

The evolution of new genes and their new enzymes often takes place after a gene duplication event followed by the adaptation of one or both of the duplicated enzymes to a particular substrate.

Most people think of enzymes as being highly specific for a particular substrate so they see this adaptation as an all-or-none affair involving a fairly drastic change in substrate binding. Creationists, in particular, are prone to this mistaken view of biochemistry so they see the evolution of a new enzyme activity as a difficult process. Sometimes they note that several amino acid substitutions are required to change substrates and they declare that this is beyond the reach of gradual evolution.

I'm going to tell you about the evolution of a new enzyme that has been caught in progress. This example will help you realize that enzymes don't have to be highly specific for a single substrate and it will help you appreciate how easy it is to evolve new substrate specificities from sloppy precursors. That's the way it probably happens in most cases.

The top diagram shows the pathways of biosynthesis of three amino acids that have branched side chains: isoleucine, valine, and leucine. Bear with me for a minute while I explain the chemistry—it will be worth it in the end.

In order to make isoleucine you need to combine two simple molecules, pyruvate and α-ketobutyrate, to make a molecule with seven carbon atoms. This molecule then undergoes three reaction to produce the six-carbon molecule α-keto-β-methylvalerate (with the loss of CO₂). Now look at the pathway for the synthesis of valine and leucine (on the right). The first step combines a molecule of pyruvate with another molecule of pyruvate to produce a six-carbon compound that is subsequently converted to the five-carbon compound α-ketoisovalerate.

The neat thing about these two pathways is that the first four steps are catalyzed by the same four enzymes! Each of these enzymes is capable of recognizing two different substrates.

For example, the first enzyme is acetohydroxy acid synthase. It can combine a pyruvate molecule with another pyruvate molecule or with α-ketobutyrate. Both reactions are catalyzed at high efficiency. The normal enzyme has a preference for α-ketobutyrate as the acceptor molecule because the concentration of α-ketobutyrate inside cells is much lower than the concentration of the donor molecule, pyruvate. This preference ensures that the rate of synthesis of isoleucine is comparable to synthesis of valine and leucine.

There are two similar genes for acetohydroxy acid synthase in some bacteria. They clearly arise from a recent gene duplication event. One of the genes encodes an enzyme with the standard preference for α-ketobutyrate but the other encodes an enzyme that prefers to combine two molecules of pyruvate. Both enzymes (AHAS I and AHAS II) catalyze both reactions but they differ in their preference for the acceptor substrate (Epelbaum et al. 1998, Steinmetz et al. 2010).

Under normal growth conditions (glucose as a carbon source) in Salmonella typhimurium, the typical enzyme that prefers α-ketobutyrate as acceptor (ASAS II) is all that's required. (You can knock out the other gene and growth isn't affected.) However, the other isozyme (ASAS I) is essential when the cells are grown on acetate as the sole carbon source. This is because in the presence of acetate the internal concentration of pyruvate is low so you need an enzyme that binds both acceptor molecules equally well.

What we have here is an example that helps us understand how homologous enzymes may have evolved in the ancient past. The ancestral enzyme was capable of catalyzing several similar reactions. Following a gene duplication event, the two separate genes evolved independently to specialize in just one of the reactions that the original enzyme could catalyze. Neither of them had to evolve an entirely new substrate binding site, they only had to hone an already existing site.

The important observation is that not all enzymes are highly specific. Even modern enzymes that catalyze common reactions can be shown to catalyze similar reactions at a low level. The important conceptual point is that ancient enzymes were certainly very sloppy and frequently catalyzed a wide range of similar reactions. This is what you expect during early evolution. You don't expect highly efficient, highly specific, enzymes to just pop into existence out of the blue.

The take-home lesson is that the evolution of two homologous enzymes that catalyze different, but similar, reactions did not arise by switching from one activity to another. Instead, they arose from a common ancestor that could catalyze both reactions.

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[The pathways are from Moran et al. (2012) Principles of Biochemsitry and the enzyme is acetohydroxy acid synthase from yeast (PDB=1T9C)]

Epelbaum, S., LaRossa, R.A., VanDyk, T.K., Elkayam, T., Chipman, D.M., and Barak, Z. (1998) Branched-chain amino acid biosynthesis in Salmonella typhimurium: a quantitative analysis. J. Bacteriol. 180:4056-4067. [PubMed Central]

Steinmetz, A., Vyazmensky, M., Meyer, D., Barak, Z.E., Golbik, R., Chipman, D.M., and Tittmann, K. (2010) Valine 375 and phenylalanine 109 confer affinity and specificity for pyruvate as donor substrate in acetohydroxy acid synthase isozyme II from Escherichia coli. Biochemistry 49:5188-5199. [PubMed]

Reading Books

Now that I've finished writing my book, I'm back into reading. I have a pile of books that I have to get through before classes start. It's going to be difficult 'cause I'm off to Brussels next week to visit my granddaughter Zoë.

I mostly read non-fiction with an emphasis on science, philosophy, history, theology, and creationism. When I'm finished with a book it's usually full of highlighted text and margin notes and many of the pages have sticky tags for quick reference. Every single one of my books becomes part of my reference library and I almost always consult them again after reading.

I can't imagine how anyone like me could ever make use of an electronic reader. I've got exactly three books on my iPad (Pride and Prejudice, Treasure Island, and Aesop's Fables) and that's only because they came with the kindle app. I will never read them.

A couple of days ago I discovered another thing you can do with a real book (paperback) that you can't do with a kindle or other reader—especially an expensive iPad. It was a horrible book that I had just finished and it felt really, really, good to throw it across the room into the waste basket. I retrieved it later on for future reference but the gesture was immensely satisfying.

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[Photo credit: My daughter flew in from Brussels a few days ago on her way to Newark. She had to take care of some business in Toronto so she stayed the night in her old room. I discovered this little scene on her bed after she had left.]

Here Be Dragons

I first met Stefaan Blancke (left) and Maarten Boudry (right) when they came to Toronto for a conference in November, 2009. A few months later I visited Maarten at the University of Gent in Belgium (Stefaan wasn't there on the day I visited) [Good News from Gent].

These young philosophers presented a paper on Methodological Naturalism that impressed me enormously. The paper was eventually published in June 2010 [Methodological Naturalism - How Not to Attack Intelligent Design Creationism].

The essence of their paper is that science is not intrinsically limited to methodological naturalism in spite of what many people—especially accommodationists—might say. (And in spite of what was said in court in Dover, Pennsylvania.) Boudry and Blanke (and Johan Braeckman) claim that science is perfectly capable of investigating supernatural claims. However, whenever scientists have done this they have discovered that the claims are either false or unsupported by evidence. Hence, science is characterized by "provisory" methodological naturalism based on empirical evidence. This is very different from "intrinsic" methodological naturalism.

Maarten Boudry has written lots more about pseudoscience in general and Intelligent Design Creationism in particular. It's all published in his thesis: Here Be Dragons. I suggest you read the whole thing!

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[Image Credit: rbh.Smaug.jpg. Smaug is from The Hobbit. It's also the favorite dragon of my colleague Craig Smibert who discovered the Smaug (Smg) gene/protein in Drosophila melanogaster.]

Physicists and Biologists

I've just finished reading evolution: a view from the 21st century by James A. Shapiro. I'll write up a full review later on but right now I just want to quote a passage from near the end of the book. He begins the paragraph with a description of those physicists who entered biology in the 1940s and 50s (e.g. Max Delbrück).

Currently another wave of physical scientists is entering the life sciences. They bring with them a much-needed and fruitful sophistication in observation at the micro level, in mathematical formulation of results, and in computational methods of data analysis. Physicists-turned-biologists have an additional advantage of lacking a formal education in the life sciences; consequently, they have not been taught to exclude from their thinking notions previously concluded to be "impossible." We can only hope that their less prejudiced backgrounds will make it easier for them to develop novel conceptual frameworks to complement the analytical and experimental techniques they are introducing.

This insightful observation has great potential beyond solving the major problems in the biological sciences and I wonder if Shapiro fully appreciates the implications.

I have no formal training in physics. I haven't the foggiest idea what quantum chromodynamics (QCD) is all about, beyond what I can read on Wikipedia. I don't have a firm grasp of general relativity and my math skills are very weak.

However, I understand that physics is grappling with unified field theory and that string theory is going nowhere. I've heard rumors that physicists can't find the Higgs boson, although I can't imagine where they might have put it. I have plenty of experience helping Ms. Sandwalk find her car keys and credit card so I've come up with a brilliant idea.

Why don't I move to physics and solve their problems? I've got all the proper qualifications, "lacking a formal education," "less prejudicial background," and I haven't been taught to exclude impossible things. I bet I could convince half a dozen of my biologist colleagues to abandon the difficult problems of biology in order to help the physicists. It shouldn't take more than a few years.

We need a name for this discovery, let's call it The Shapiro Conjecture.¹

Meanwhile, I welcome all those physicists who know nothing about evolution, protein structure, genetics, physiology, metabolism, and ecology. That's just what we need in the biological sciences to go along with all the contributions made by equally ignorant creationists.

AFTERTHOUGHT: Biologists have been using computers to analyze complex data sets for over fifty years and we're pretty sophisticated at making observations at the micro level. Why do we need physicists to show us these techniques?

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1. See The Salem Conjecture.

Magical Mirrors

Sometimes it's fun to set aside trivial questions like evolution vs. creationism and address the really important questions in life. The last time we did this was when we discussed the proper way to hang toilet paper [Gil Dodgen Explains the Salem Conjecture].

Chad Orzel of Uncertain Principles has posted a link to Rhett Allain at DOT.PHYSICS who asks one of those big questions that we've all pondered obsessively ...

Why do mirrors reverse left and right, but they don’t reverse up and down?.

Please proceed with caution because Rhett comes about as close as one can to answering the question—thus removing it from the top ten list of mysteries. If you want to preserve your childhood fantasies about the magical properties of mirrors then I advise you to ignore this posting.

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The IDiots Respond

I didn't think it would take very long for the Intelligent Design Creationists to respond to my posting on Evolution Is a Fact and a Theory. After all, it's not something they can be very happy about since it reveals how clueless they've been when discussing evolution.

David Klinghoffer, Senior Fellow at the Discovery Institute, gets the ball rolling with: Evolution in Fact and Theory, Revisited. Let's see how he does ...

Around the 30th anniversary of the publication of Stephen Jay Gould's essay with a similar name, Larry Moran has reposted his essay "Evolution Is a Fact and a Theory." His article begins by blithely accepting the confused terminological protocol that uses the same word, "evolution," to describe very different things: a) the observation that life forms have changed over vast stretches of time, and b) a set of proposed observations regarding how, by what mechanisms, the forms of life have changed.

You don't have to be a philosopher to sense that using the same word to designate different things, in a contentious context like this, is bound to result in confusion if not abuse. It surprises me that folks in biology don't establish a more precise vocabulary, unless the confusion serves a purpose they'd rather not admit even to themselves.

Hmmm ... imagine using a word to describe a field of study while using the same word when you refer to the theory behind it. Gravity, economics, Intelligent Design Creationism, history, epistemology, black holes, plate tectonics, the Bible, music, atoms, cells, politics, ethics, chemical bonds, the weather, .....

In any event, regarding the assertion contained in Moran's title, Casey's formulation has a lot to recommend it:

When evolution is defined as mere change over time within species, no one disputes that such evolution is a fact. But neo-Darwinian evolution -- the great claim that unguided natural selection acting upon random mutations is the driving force that produced the complexity of life -- has many scientific problems because such random and unguided processes do not build new complex biological features. Neo-Darwinian evolution is a theory that has been falsified by the evidence.

The proper definition of evolution is [What Is Evolution?] ...

Evolution is a process that results in heritable changes in a population spread over many generations.

Is it too much to ask that the IDiots get the definition of evolution correct? (It's a rhetorical question.) Evolution is not just change. It has to be heritable change and it has to occur in a population, not an individual. And there can be many populations within a species. You'd think that after several decades the IDiots would at least try and understand the subject they're attacking!

As for "neo-Darwinian" evolution, that's part of evolutionary theory. Evolution by natural selection is a fact. We know that it doesn't explain everything about evolution because there are other mechanisms of evolution that are known to have played a role in the history of life. Can some combination of these mechanisms result in the evolution of complex biological features? Yes, of course they can. It's wishful thinking on the part of the IDiots to claim that evolution can never do that. The theory of evolution by natural selection has not been falsified. Neither has evolution by random genetic drift. There are many viable theories of speciation. Punctuated equilibria seem to be the best explanation for some, but not all lineages in the fossil record. There are lots of theories about mass extinctions. Mutationism seems like a reasonable possibility. Molecular drive is probably restricted to very particular cases. Lamarckian inheritance hasn't been totally ruled out but it's not very likely.

Evolutionary theory is a lot more complicated that the IDiots think. I've spent the better part of 25 years tying to educate them about evolution (fact and theory). How come, after decades of supposedly trying, they still think that "Darwinism" or "neo-Darwinism" is all there is to modern evolutionary theory?

Is it because they're IDiots? (That's a rhetorical question.)

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Either tomato plants have a brain or nature is designed

You really can't make this stuff up! No matter how stupid you think the IDiots are, they can always surprise you. Yesterday it was Denyse O'Leary who provided us with some comic relief on Uncommom Descent: Either tomato plants have a brain or nature is designed.

I'm beginning to think that Uncommon Descent is a spoof site designed make Intelligent Design Creationists look silly.

It's working.

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Evolution Is a Fact and a Theory

This year is the 30th anniversary of the publication of Stephen Jay Gould's famous essay, Evolution as Fact and Theory in Discover magazine (May 1981).¹

Back in 1993, I wrote a essay for talk.origins promoting the basic concepts that Gould, and others, advocated [Evolution is a Fact and a Theory (1993)]. This essay has been modified and updated several times since then—the latest version was on my website [Evolution Is a Fact and a Theory (2007)].

You would think that the simple concept described in all those articles would be widely understood by creationists but that's not the case. Even today, there are creationists who struggle to understand the difference between fact and theory. That's why I'm posting the 2011 version of my essay.

Evolution Is a Fact and a Theory
When non-biologists talk about biological evolution they often get confused over several different meanings of the word "evolution." On the one hand, there's the question of whether or not modern organisms have evolved from older ancestral organisms or whether modern species are continuing to change over time. On the other hand, there are questions about the mechanism of the observed changes... how did evolution occur? Biologists consider the existence of biological evolution to be a fact. It can be demonstrated today and the historical evidence for its occurrence in the past is overwhelming. However, biologists readily admit that they are less certain of the exact mechanism of evolution; there are several theories of the mechanisms of evolution. Stephen J. Gould has put this as well as anyone else:

In the American vernacular, "theory" often means "imperfect fact"--part of a hierarchy of confidence running downhill from fact to theory to hypothesis to guess. Thus the power of the creationist argument: evolution is "only" a theory and intense debate now rages about many aspects of the theory. If evolution is worse than a fact, and scientists can't even make up their minds about the theory, then what confidence can we have in it? Indeed, President Reagan echoed this argument before an evangelical group in Dallas when he said (in what I devoutly hope was campaign rhetoric): "Well, it is a theory. It is a scientific theory only, and it has in recent years been challenged in the world of science—that is, not believed in the scientific community to be as infallible as it once was."

Well evolution is a theory. It is also a fact. And facts and theories are different things, not rungs in a hierarchy of increasing certainty. Facts are the world's data. Theories are structures of ideas that explain and interpret facts. Facts don't go away when scientists debate rival theories to explain them. Einstein's theory of gravitation replaced Newton's in this century, but apples didn't suspend themselves in midair, pending the outcome. And humans evolved from ape-like ancestors whether they did so by Darwin's proposed mechanism or by some other yet to be discovered.

Moreover, "fact" doesn't mean "absolute certainty"; there ain't no such animal in an exciting and complex world. The final proofs of logic and mathematics flow deductively from stated premises and achieve certainty only because they are not about the empirical world. Evolutionists make no claim for perpetual truth, though creationists often do (and then attack us falsely for a style of argument that they themselves favor). In science "fact" can only mean "confirmed to such a degree that it would be perverse to withhold provisional consent." I suppose that apples might start to rise tomorrow, but the possibility does not merit equal time in physics classrooms.

Evolutionists have been very clear about this distinction of fact and theory from the very beginning, if only because we have always acknowledged how far we are from completely understanding the mechanisms (theory) by which evolution (fact) occurred. Darwin continually emphasized the difference between his two great and separate accomplishments: establishing the fact of evolution, and proposing a theory—natural selection—to explain the mechanism of evolution.

Stephen J. Gould, "Evolution as Fact and Theory"; Discover, May 1981

Gould is stating the prevailing view of the scientific community. In other words, the experts on evolution consider it to be a fact. This is not an idea that originated with Gould. The same point was made by Theodosius Dobzhansky eight years earlier—and by others before him.

Let me try to make crystal clear what is established beyond reasonable doubt, and what needs further study, about evolution. Evolution as a process that has always gone on in the history of the earth can be doubted only by those who are ignorant of the evidence or are resistant to evidence, owing to emotional blocks or to plain bigotry. By contrast, the mechanisms that bring evolution about certainly need study and clarification. There are no alternatives to evolution as history that can withstand critical examination. Yet we are constantly learning new and important facts about evolutionary mechanisms.

Theodosius Dobzhansky "Nothing in Biology Makes Sense Except in the Light of Evolution" American Biology Teacher vol. 35 (March 1973) reprinted in Evolution versus Creationism, J. Peter Zetterberg ed., ORYX Press, Phoenix AZ 1983

Dobzhansky's point is that evolution is occurring and has occurred in the
past. These facts are not questioned by anyone who is familiar with the evidence for evolution. He and Gould both knew that there are people who do have doubts about evolution. The scientists' goal is not so much to convince the doubters but to stop them from claiming that evolution is "only" a theory.

It is absolutely safe to say that if you meet somebody who claims not to believe in evolution, that person is ignorant, stupid or insane (or wicked, but I’d rather not consider that).

Richard Dawkins
This concept isn't so hard to understand when you are talking about gravity. Gravity is a fact but scientists still have a theory of gravity to explain how gravity works. The anti-evolutionists will not concede that the same distinction applies to the facts of evolution and evolutionary theory. They continue to proclaim that evolution (the fact) is "only a theory." Dobzhansky suggests that these anti-evolutionists are either ignorant of the evidence or resistant to the evidence. I think he should have entertained the possibility that some of the knowledgeable anti-evolutionists are well aware of the distinction but choose to lie to their audience.

Note that I used the term "evolutionary theory" rather than "the theory of evolution." That's because there's no such thing as "the theory of evolution" and it's time we stopped using that phrase. In its place we talk about evolutionary theory that encompasses a wide variety of ideas ranging from the theories of population genetics to models of how speciation occurs.

What are some of the facts that demonstrate evolution? Lewontin explains,

It is time for students of the evolutionary process, especially those who have been misquoted and used by the creationists, to state clearly that evolution is a fact, not theory, and that what is at issue within biology are questions of details of the process and the relative importance of different mechanisms of evolution. It is a fact that the earth with liquid water, is more than 3.6 billion years old. It is a fact that cellular life has been around for at least half of that period and that organized multicellular life is at least 800 million years old. It is a fact that major life forms now on earth were not at all represented in the past. There were no birds or mammals 250 million years ago. It is a fact that major life forms of the past are no longer living. There used to be dinosaurs and Pithecanthropus, and there are none now. It is a fact that all living forms come from previous living forms. Therefore, all present forms of life arose from ancestral forms that were different. Birds arose from nonbirds and humans from nonhumans. No person who pretends to any understanding of the natural world can deny these facts any more than she or he can deny that the earth is round, rotates on its axis, and revolves around the sun.

The controversies about evolution lie in the realm of the relative importance of various forces in molding evolution.

R. C. Lewontin "Evolution/Creation Debate: A Time for Truth"
Bioscience 31, 559 (1981) reprinted in Evolution
versus Creationism, op cit.

The sad thing about the Gould, Dobzhansky, and Lewontin articles is that they were written so long ago but they continue to be relevant today. An entire generation has grown up since Dobzhansky's 1973 essay was published in American Biology Teacher yet we still have political leaders who question the scientific fact of evolution.

This ignorance can't be due to the lack of education since the fact/theory concept has been explained in introductory biology books that are used in colleges and universities (and in some of the better high schools). For example, in some of the best such textbooks from twenty years ago, we found:

Today, nearly all biologists acknowledge that evolution is a fact. The term theory is no longer appropriate except when referring to the various models that attempt to explain how life evolves... it is important to understand that the current questions about how life evolves in no way implies any disagreement over the fact of evolution.

Neil A. Campbell, Biology 2nd ed., 1990, Benjamin/Cummings, p. 434

Also:

Since Darwin's time, massive additional evidence has accumulated supporting the fact of evolution--that all living organisms present on earth today have arisen from earlier forms in the course of earth's long history. Indeed, all of modern biology is an affirmation of this relatedness of the many species of living things and of their gradual divergence from one another over the course of time. Since the publication of The Origin of Species, the important question, scientifically speaking, about evolution has not been whether it has taken place. That is no longer an issue among the vast majority of modern biologists. Today, the central and still fascinating questions for biologists concern the mechanisms by which evolution occurs.

Helena Curtis and N. Sue Barnes, Biology 5th ed. 1989,
Worth Publishers, p. 972

One of the best introductory books on evolution (as opposed to introductory biology) is that by Douglas J. Futuyma. In the 2nd edition back in 1986 he makes the following comment:

A few words need to be said about the "theory of evolution," which most people take to mean the proposition that organisms have evolved from common ancestors. In everyday speech, "theory" often means a hypothesis or even a mere speculation. But in science, "theory" means "a statement of what are held to be the general laws, principles, or causes of something known or observed." as the Oxford English Dictionary defines it. The theory of evolution is a body of interconnected statements about natural selection and the other processes that are thought to cause evolution, just as the atomic theory of chemistry and the Newtonian theory of mechanics are bodies of statements that describe causes of chemical and physical phenomena. In contrast, the statement that organisms have descended with modifications from common ancestors--the historical reality of evolution--is not a theory. It is a fact, as fully as the fact of the earth's revolution about the sun. Like the heliocentric solar system, evolution began as a hypothesis, and achieved "facthood" as the evidence in its favor became so strong that no knowledgeable and unbiased person could deny its reality. No biologist today would think of submitting a paper entitled "New evidence for evolution;" it simply has not been an issue for a century.

Douglas J. Futuyma, Evolutionary Biology, 2nd ed., 1986, Sinauer Associates, p. 15

This is not an argument from authority. I'm simply pointing out that the distinction between evolutionary facts and evolutionary theory has been explained over and over for the past half century and there's no excuse for not knowing what scientists think about evolution.

Evolutionary Theory

There are several possible mechanisms of evolution.There are many people who reject evolution for religious reasons. In general these readers oppose both the fact of evolution and evolutionary theory, although some anti-evolutionists have come to realize that there is a difference between the two concepts. That is why we see some leading anti-evolutionists admitting to the fact of "microevolution"—they know that evolution can be demonstrated. These people will not be convinced of the "facthood" of (macro)evolution by any logical argument and it is a waste of time to make the attempt. The best that we can hope for is that they understand the argument that they oppose. Even this simple hope is rarely fulfilled.

There are some people who are not anti-science but still claim that evolution is "only" a theory that can't be proven. This group needs to distinguish between the fact that evolution occurs and evolutionary theories about the mechanisms of evolution. But there's an additional point that needs to be emphasized. Some of the proposed mechanisms of evolution, such as natural selection and random genetic drift, are facts, not speculations. We know for a fact that both these mechanisms occur in living populations. These are not "theoretical models" of evolution, they actually occur. They are part of evolutionary theory because, in many cases, we don't know for sure which one predominates in a particular case—or even if there might be another mechanism such as Lamarckian inheritance, molecular drive, or mutationism.

Fact of Evolution

Chimps and humans share a common ancestor.Similarly, there are degrees of facthood. Some facts that are easy to demonstrate and others are more circumstantial. Examples of evolution that are readily apparent include the fact that modern populations are evolving and the fact that two closely related species share a common ancestor. The evidence that Homo sapiens and chimpanzees share a recent common ancestor falls into this category. There is so much evidence in support of this aspect of primate evolution that it qualifies as a fact by any common definition of the word "fact."

This is an important point. It is not, by any stretch of the imagination, a "theory" that humans and chimps share a common ancestor. We know enough about the history of life to state that this is a scientific fact.

In other cases, the available evidence is less strong. For example, the relationships of some of the major phyla are still being worked out. Also, the statement that all organisms have descended from a single common ancestor is strongly supported by the available evidence, and there is no opposing evidence. However, it is not yet appropriate to call this a "fact" since it's possible that there were several independent life forms that exchanged genes early on in evolution. This would mean that modern species have descended from more than one common ancestor. Most of us don't think this is very likely but the possibility exists. Common descent may not be a hard fact but it's not part of evolutionary theory either. Evolutionary theory is silent about most aspects of the unique history of life on this planet just as gravitational theory is silent about the unique formation of an eight-planet solar system around an average star at the edge of the Milky Way galaxy. The history of life and the formation of our solar system have to be consistent with what we know about evolution and gravity but neither evolutionary theory nor gravitational theory predict what that history should be.

Finally, there is an epistemological argument against evolution as fact. Some philosophers point out that nothing in science can ever be "proven" and this includes evolution. According to this argument, the probability that evolution is the correct explanation of the origin of chimps and humans may approach 99.9999...9% but it will never be 100%. Thus, the common ancestry of chimps and humans can never be a fact. This kind of argument might be appropriate in a philosophy class (it is essentially correct) but it won't do in the real world. A "fact," as Stephen J. Gould pointed out (see above), means something that is so highly probable that it would be silly not to accept it. This point has also been made by others who contest the nit-picking epistemologists.

The honest scientist, like the philosopher, will tell you that nothing whatever can be or has been proved with fully 100% certainty, not even that you or I exist, since we might be dreaming the whole thing. Thus there is no sharp line between speculation, hypothesis, theory, principle, and fact, but only a difference along a sliding scale, in the degree of probability of the idea. When we say a thing is a fact, then, we only mean that the probability of it being true is high—so high that we are not bothered by doubt about it and are ready to act accordingly. By this use of the term "fact"—the only proper definition—evolution is a fact. For the evidence in favor of it is as voluminous, diverse, and convincing as in the case of any other well established fact of science concerning the existence of things that cannot be directly seen, such as atoms, neutrons, or solar gravitation ....

So enormous, ramifying, and consistent has the evidence for evolution become that if anyone could now disprove it, I should have my conception of the orderliness of the universe so shaken as to lead me to doubt even my own existence. If you like, then, I will grant you that in an absolute sense evolution is not a fact, or rather, that it is no more a fact than that you are hearing or reading these words.

H. J. Muller, "One Hundred Years Without Darwin Are Enough"
School Science and Mathematics 59, 304-305. (1959)
reprinted in Evolution versus Creationism op cit.

In any meaningful sense evolution is a fact, but there are various theories concerning the mechanism of evolution.

Creationists will never accept that evolution is a fact and they will continue to lump the history of life into "the theory of evolution." They will never accept that evolutionary theory includes many models and many proven mechanisms. They insist that it's all "Darwinism." I don't expect to change their minds—I'm not that naive—but I do expect them to learn the truth about what scientists are saying, even if it's only to criticize the science. Surely that's not too much to ask?

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1. Republished in Hen's Teeth and Horse's Toes, New York: W. W. Norton & Company, 1983, pp. 253-262.

Dennis Markuze Arrested

According to Montreal police a suspect has been arrested in the "David Mabus" case. They don't say who it was but we all know it's Dennis Markuze [Montreal police make arrest in "Mabus" case on online death threats].

For a very detailed outline of this case see: Case Study: How a notorious spammer was brought down via Twitter.

There is a God! I have removed comment moderation on Sandwalk

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Pervasive Transcription

"Pervasive transcription" refers to the idea that a large percentage of the DNA in mammalian genomes is transcribed. The idea became popular with the publication of the ENCODE results back in 2007 (Birney et al. 2007). Their results indicated that at least 93% of the human genome was transcribed at one time or another or in one tissue or another.

The result suggests that most of the genome consists of functional DNA. This pleases those who are opposed to the concept of junk DNA and it delights those who think that non-coding RNAs are going to radically change our concept of biochemistry and molecular biology. The result also pleased the creationists who were quick to point out that junk DNA is a myth [Junk & Jonathan: Part 6—Chapter 3, Most DNA Is Transcribed into RNA].

THEME:
Transcription
The original ENCODE paper used several different technologies to arrive at their conclusion. Different experimental protocols gave different results and there wasn't always complete overlap when it came to identifying transcribed regions of the genome. Nevertheless, the combination of results from three technologies gave the maximum value for the amount of DNA that was transcribed (93%). That's pervasive transcription.

The implication was that most of our genome is functional because it is transcribed.¹ The conclusion was immediately challenged on theoretical grounds. According to our understanding of transcription, it is expected that RNA polymerase will bind accidentally at thousands of sites in the gnome and the probability of initiating the occasional transcript is significant [How RNA Polymerase Binds to DNA]. Genes make up about 30% of our genome and we expect that this fraction will be frequently transcribed. The remainder is transcribed at a very low rate that's easily detectable using modern technology. That could easily be junk RNA [How to Frame a Null Hypothesis] [How to Evaluate Genome Level Transcription Papers].

There were also challenges on technical grounds; notably a widely-discussed paper by van Bakel et al, 2010) from the labs of Ben Blencowe and Tim Hughes here in Toronto. That paper claimed that some of the experiments performed by the ENCODE group were prone to false positives [see Junk RNA or Imaginary RNA?]. They concluded,

We conclude that, while there are bona fide new intergenic transcripts, their number and abundance is generally low in comparison to known genes, and the genome is not as pervasively transcribed as previously reported.

The technical details of this dispute are beyond the level of this blog and, quite frankly, beyond me as well since I don't have any direct experience with these technologies. But let's not forget that aside from the dispute over the validity of the results, there is also a dispute over the interpretation.

As you might imagine, the pro-RNA, anti-junk, proponents fought back hard led by their chief, John Mattick, and Mark Gerstein (Clark et al., 2011). The focus of the counter-attack is on the validity of the results published by the Toronto group. Here's what Clark et al. (2011) conclude after their re-evaluation of the ENCODE results.

A close examination of the issues and conclusions raised by van Bakel et al. reveals the need for several corrections. First, their results are atypical and generate PR curves that are not observed with other reported tiling array data sets. Second, characterization of the transcriptomes of specific cell/tissue types using limited sampling approaches results in a limited and skewed view of the complexity of the transcriptome. Third, any estimate of the pervasiveness of transcription requires inclusion of all data sources, and less than exhaustive analyses can only provide lower bounds for transcriptional complexity. Although van Bakel et al. did not venture an estimate of the proportion of the genome expressed as primary transcripts, we agree with them that “given sufficient sequencing depth the whole genome may appear as transcripts” [2].

There is already a wide and rapidly expanding body of literature demonstrating intricate and dynamic transcript expression patterns, evolutionary conservation of promoters, transcript sequences and splice sites, and functional roles of “dark matter” transcripts [39]. In any case, the fact that their expression can be detected by independent techniques demonstrates their existence and the reality of the pervasive transcription of the genome.

The same issue of PLoS Biology contained a response from the Toronto group (van Bakel et al. 2011). They do not dispute the fact that much of the genome is transcribed since genes (exons + introns) make up a substantial portion and since cryptic (accidental) transcription is well-known. Instead, the Toronto group focuses on the abundance of transcripts from extra-genic regions and its significance.

We acknowledge that the phrase quoted by Clark et al. in our Author Summary should have read “stably transcribed”, or some equivalent, rather than simply “transcribed”. But this does not change the fact that we strongly disagree with the fundamental argument put forward by Clark et al., which is that the genomic area corresponding to transcripts is more important than their relative abundance. This viewpoint makes little sense to us. Given the various sources of extraneous sequence reads, both biological and laboratory-derived (see below), it is expected that with sufficient sequencing depth the entire genome would eventually be encompassed by reads. Our statement that “the genome is not as not as pervasively transcribed as previously reported” stems from the fact that our observations relate to the relative quantity of material detected.

Of course, some rare transcripts (and/or rare transcription) are functional, and low-level transcription may also provide a pool of material for evolutionary tinkering. But given that known mechanisms—in particular, imperfections in termination (see below)—can explain the presence of low-level random (and many non-random) transcripts, we believe the burden of proof is to show that such transcripts are indeed functional, rather than to disprove their putative functionality.

I'm with my colleagues on this one. It's not important that some part of the genome may be transcribed once every day or so. That's pretty much what you might expect from a sloppy mechanism—and let's be very clear about this, gene expression is sloppy.

You can't make grandiose claims about functionality based on such low levels of transcription. (Assuming the data turns out to be correct and there really is pervasive low-level transcription of the entire genome.)

This is a genuine scientific dispute waged on two levels: (1) are the experimental results correct? and (2) is the interpretation correct? I'm delighted to see these challenges to "dark matter" hyperbole and the ridiculous notion that most of our genome is functional. For the better part of a decade, Mattick and his ilk had free rein in the scientific literature [How Much Junk in the Human Genome?] [Greg Laden Gets Suckered by John Mattick].

We need to focus on re-educating the current generation of scientists so they will understand basic principles and concepts of biochemistry. The mere presence of an occasional transcript is not evidence of functionality and the papers that made that claim should never have gotten past reviewers.

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1. Not just an "implication" since in many papers that conclusion is explicitly stated.

Clark, M.B., Amaral, P.P., Schlesinger, F.J., Dinger, M.E., Taft, R.J., Rinn, J.L., Ponting, C.P., Stadler, P.F., Morris, K.V., Morillon, A., Rozowsky, J.S., Gerstein, M.B., Wahlestedt, C., Hayashizaki, Y., Carninci, P., Gingeras, T.R., and Mattick, J.S. (2011) The Reality of Pervasive Transcription. PLoS Biol 9(7): e1000625. [doi: 10.1371/journal.pbio.1000625].

Birney, E., Stamatoyannopoulos, J.A. et al. (2007) Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447:799-816. [doi:10.1038/nature05874]

van Bakel, H., Nislow, C., Blencowe, B. and Hughes, T. (2010) Most "Dark Matter" Transcripts Are Associated With Known Genes. PLoS Biology 8: e1000371 [doi:10.1371/journal.pbio.1000371]

van Bakel, H., Nislow, C., Blencowe, B.J., and Hughes, T.R.. (2011) Response to "the reality of pervasive transcription". PLoS Biol 9(7): e1001102. [doi:10.1371/journal.pbio.1001102]