Gene Genie #10

 
Gene Genie #10 was posted Ryan Gregory on Genomicron [Gene Genie #10 -- The Canada Day Ultraspectacular Edition].

Visible Mutations and Evolution by Natural Selection

A recent posting [Darwin Still Rules, but Some Biologists Dream of a Paradigm Shift] raised the issue of adaptationism. The controversy is over the main mechanism of genetic change in evolving populations. Adaptationists tend to attribute as much as possible to natural selection while pluralists emphasize the important role of other mechanisms of evolution, like random genetic drift.

There seems to be little doubt that most of the fixed alleles at the molecular level are probably neutral in their effect. Thus, they have been fixed by random genetic drift. This includes many amino acid substitutions in proteins. Even though these substitutions change the structure of a protein by a small amount, it does not seem reasonable to assume that they have all been selected.

Most adaptationists are content to concede this point (although there are holdouts). However, they draw the line at more "visible" mutations. According to this group, the vast majority of "visible" mutations are subject to natural selection and therefore most fixed alleles with a "visible" phenotype are adaptations. The argument seems to be that once a mutation produces a "visible" phenotype then it is not appropriate to suggest that it might be neutral with respect to natural selection. The line seems to be drawn somewhere above differences in the amino acid composition of proteins but it's not clear exactly where.

p-ter is one of those who are very reluctant to admit that a visible character could have been fixed by accident. He has posted a short article on Gene Expression [Do phenotypes evolve neutrally?]. I recommend that you read the comments to see examples of the extreme version of adaptationism. Most of these adaptationists will even argue that human blood types are adaptive. The idea that most native North Americans have type O blood is due to some undefined selective advantage and not to accident.

This argument has been going on for several decades. As usual, it's not about the existence of natural selection or random genetic drift. It's about their relative importance in evolution. To reiterate, the adaptationists believe that almost all mutations with a visible phenotype have been fixed by natural selection. The pluralists think that many of them are neutral and have been fixed by accident. The adaptationists make a distinction between what happens at the molecular level and what happens at the "visible" level while the pluralists think the same mechanims are operating at both levels.

Richard Lewontin uses the example of the Indian and African rhinoceros to focus the debate. The African rhinoceros has two horns while the Indian rhinoceros has only one. The question is whether this difference is due to natural selection—is two horns better than one in Africa? Or, is it just an accident of evolution that one species has two horns while the other has only one?



I don't understand why the adaptationist camp is so reluctant to admit that some visible characters can be fixed by random genetic drift. The idea that every feature of an organism has to be an adaptation seems so out of touch with our modern understanding of evolution that I'm really puzzled by the vehemence with which adaptationists defend their orthodoxy. It seems as though admitting that visible phenotypes might be non-adaptive is a major threat to their worldview.

Monday's Molecule #33

 
Today's molecule is complex. The short common name of this molecule is sufficient but you're more than welcome to supply the IUPAC name if you know it. There's a direct connection between this Monday's Molecule and Wednesday's Nobel Laureate. (Hint: this molecule is not mentioned in the description of the award but the class of molecules to which it belongs is mentioned.)

The reward (free lunch) goes to the person who correctly identifies the molecule and the Nobel Laureate(s). Previous free lunch winners are ineligible for one month from the time they first collected the prize. There's only one (Marc) ineligible candidates for this Wednesday's reward since many recent winners haven't collected their prize. The prize is a free lunch at the Faculty Club.

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UPDATE: The molecule is ergosterol, a plant sterol that is a precursor to vitamin D. Ultraviolet irradiation converts ergosterol to vitamin D₂.

Happy Canada Day

 


HAPPY

CANADA

DAY

Canada's official birthday was yesterday, July 1, but everyone gets a holiday today to celebrate.

Nobel Laureate: Albert von Szent-Györgyi Nagyrapolt

 
The Nobel Prize in Physiology or Medicine 1937.

"for his discoveries in connection with the biological combustion processes, with special reference to vitamin C and the catalysis of fumaric acid"

Albert von Szent-Györgyi Nagyrapolt (1893 - 1986 ) received the Nobel Prize in Physiology or Medicine for his work on the biochemistry of combustion, or respiration as we now know it. In most cases when we read the presentation speeches for past Nobel Prizes we recognize the seminal insights that have led to a better understanding of science. This recognition is usually even more obvious when we review the Nobel Lecture of the prize winner [Szent-Gyorgyi Lecture].

In this case the presentation speech seems hopelessly confusing and it's difficult to see any connection between our current understanding of metabolism and the view presented in 1937. Szent-Gyorgi worked on the metabolism of vitamin C and on the role of fumarate in basic metabolism. (Fumarate was Monday's Molecule #32.) Szent-Gyorgi thought that vitamin C was an essential cofoactor in metabolism but we now know that it plays only a minor role [Scurvy and Vitamin C]. He also though that fumarate was a cofactor bound to the surface of an enzyme—it is not. Furthermore he thought that fumarate was part of a reductive pathway where hydrogen atoms were taken up from the food and passed from oxaloacetate to malate to fumarate to succinate and then to a cytochrome complex where they were eventually combined with water. We now know that this pathway part of a large pathway (the Krebs cycle [Nobel Laureates: Hans Krebs]) that operates in the opposite direction. We also know that it is electrons, not protons, that carry the energy of metabolism.

Read the presentation speech below to see the state of knowledge in 1937. Keep in mind that at the time there were other scientists, notably Hans Krebs, who were on the right track.

Your Majesty, Your Royal Highnesses, Ladies and Gentlemen.

The Staff of Professors of the Caroline Institute, pursuant to the task devolving upon them by the terms of the will of Alfred Nobel, have awarded the Prize for Physiology or Medicine for the year 1937 to Professor Albert von Szent-Györgyi, in recognition of his discoveries concerning the biological combustion processes with especial reference to vitamin C and to the fumaric acid catalyst. The wording of the above sentence indicates that the mechanism of biological oxidation has been investigated beyond the great discoveries in this field made by Otto Warburg, Heinrich Wieland, and their successors. Their systems of catalysts for oxidation have been shown to be dependent on Szent-Györgyi's new catalysts.

It was generally known before that combustion liberates energy in living cells which can be employed there without loss - directly for the building up of new substances - for storage or for the building of functioning cell structures. The building up of living organisms then is dependent in essential respects on combustion, which is guided by catalyst systems. Thus catalyst systems are conditional for the building up of living organisms. Consequently in the unknown period during which organic life originated, the formation of these and other catalyst systems must have preceded the completion of the living animal organisms.

Preferably I should wish to confine my remarks to the new conquistador from Szeged. The survey is however of higher importance on this occasion, and moreover the course of the events is dramatically concentrated. Each one of the three has conquered new ground by intuitive daring and skill. Szent-Györgyi's greatest achievement has intimately linked up the accomplishments of the two others and of their successors, giving us for the first time a picture of a coherent oxidation process - of the interplay of three catalyst systems and the oxidation thereby in metabolism.

Warburg, who always stood alone with some few faithful co-workers, is the foremost pioneer, and he had to overcome the greatest difficulties. At this day there is none who can any longer throw doubt on his discoveries, but that was not so, when in 1931 underestimated by the majority, he was awarded the Nobel Prize by the Caroline Institute. He has shown that the inert oxygen, with which the red blood corpuscles are fully loaded, is taken up from them by a catalyst system to which many red pigments belong (for brevity's sake called «the red system»). These are related to the red blood pigment. They contain as active groups (for the most part) iron and specific proteins. In this system the oxygen combines with the iron during varying periods of time. In the case of the most rapid catalysts, it combines with the iron, is converted into a lively, reactively disposed form and is delivered - all at a speed that gives a flowing stream of active oxygen from the catalyst system. One thought that this active oxygen oxidized directly. That is not the way however. On the contrary, the active oxygen meets hydrogen - but that is another story, belonging to Szent-Györgyi's great discovery. The manner in which the life-giving active oxygen's dramatic encounter in the darkness of the cells ensues, had been unknown ever since the morning of time until, in 1933, Szent-Györgyi carried out some experiments which proved to be the prelude to the revelation of the secret.

For the moment I will leave oxygen, and direct the attention to the first, apparently unimportant, experiments carried out by Wieland. These led him to the conception of an idea, which was destined to carry him on to the disclosure of an extensive part of the mechanism of oxidation. A large number of investigators were soon attracted by Wieland's opinion. This seemed to be at variance with the oxygen activation - at any rate that was the view of a majority. This apparent inconsistency was never considered by Szent-Györgyi, nor by Warburg.

Wieland had observed that palladium is capable of absorbing hydrogen from certain organic compounds, which means their partial combustion or oxidation. Through the cooperation of many investigators the presence was revealed of extensive metal-free catalyst systems, the effect of which was shown to consist in the removal of hydrogen from metabolic substances, in agreement with Wieland's concept. These catalysts were given a name in common: dehydrogenases (hydrogen-removers, hydrogen-absorbers, or hydrogen-transporters) and the idea was held pretty generally that the hydrogen activated by this system would be capable of reacting directly with the inert oxygen molecules. Hydrogen superoxide was supposed to form an intermediate product. That is not the highway of oxidation however. On the contrary, the hydrogen first meets Szent-Györgyi's catalyst system from a different side to the one where the activated oxygen flows into it from the «red system». That again is another story, which also belongs to Szent-Györgyi's great discovery. From 1925 onwards he had been investigating a number of hydrogen-absorbers. Previously to anyone else he formed the view of these as members of a catalyst system in the service of oxidation (in other quarters loosely conceived of as being auxiliary catalysts of some kind for fermentation). He was also occupied with experiments on a yellow substance, termed flave by him, while his investigation regarding vitamin C was being completed, and conducted on to the isolation of that substance, enabling him later to insert it in the catalyst system of certain hydrogen-removers. Vitamin C and another substance, containing sulphur as a hydrogen-removing group and defined by Sir Frederick Gowland Hopkins and others, were however until 1934 the only substances belonging to the hydrogen-transporters in the oxidation-chain that had been isolated. The rank that they possess as catalysts is dependent on the velocity of the hydrogen-transportation and the degree of the activation of the hydrogen - problems that still await a satisfactory solution. On the other hand, Hugo Theorell succeeded in 1934 in isolating, in Warburg's laboratory, the first really rapid hydrogen-transporter, called «the yellow enzyme». He could also show that it was a phosphoric-acid ester of vitamin B2, linked to a specific protein. Warburg and Christian, in 1935, defined the nature of the active group in two other dehydrogenases, colourless and metal-free (co-ferment and co-zymase), which had long frustrated the attempts of other investigators. One of them was the catalyst that Szent-Györgyi had placed in this section of the oxidation-chain.

The magnificent series of Szent-Györgyi's discoveries commenced in 1933. They were carried out and pursued at Szeged with extraordinary rapidity and precision. His clear vision for essentials induced him, in spite of his isolation of ascorbic acid and of his identification of it with the so-termed vitamin C - a feat that was justly hailed with enthusiasm - to hand over to others for the time being the tempting pursuit of the further development of that discovery, and to devote the whole of his energy to the problem of combustion, notwithstanding the difficulties it presented. Many investigators had been working at the so-called plant acids in the muscular system, and had observed their capacity for intensifying oxidation in that tissue. The readiest explanation however of how that came about, viz. that they are easily combusted themselves, simply did not fit in with Szent-Györgyi's intuitive perception. By elaborating reliable methods of analysis for the substances in question, and by means of consistent experiments, he and his co-workers proved that the plant acids were not consumed by combustion, were not ordinary nutrient substances, but were on the contrary themselves active groups of catalysts which served to maintain the combustion without themselves suffering any diminution thereby. The process involves a peregrination of hydrogen more intricate than the adventurous journeys of Odysseus, though more rapid. Hydrogen is released out of the metabolic substances, probably through cooperation between Szent-Györgyi's and Warburg's co-ferment and Theorell's yellow enzyme, and encounters the plant acids, entering in that way Szent-Györgyi's's system. These acids transfer the system into the order: oxalacetic acid, malic acid, fumaric acid, and succinic acid, then, in the form of active hydrogen, to encounter the active oxygen from «the red system» and form water and free energy - a series of providentially subdued explosions which I alluded to before as a dramatic encounter. The plant acids act as catalysts by cooperation with specific proteins, and the effect of the yellow enzyme probably extends some way into this Szent-Györgyi's intermediate system.

Thus, the oxygen-activation in the red iron system and hydrogen-transfer from nutrients by the yellow metal-free system along with co-agents have been united by Szent-Györgyi through the discovery of this intermediate system. The interplay of «the red system»'s cytochrome-group and the yellow enzyme might probably also, according to Theorell, proceed directly. The flaws are numerous, but not of a character to constitute any essential breach in the highway of the oxidation-chain. Numerous ramifications of the latter however already begin to be discernible.

It is of especially great importance that at least two vitamins - C and B2, and possibly B1, and P - are in cooperation in the oxidation chain and are catalysts, illustrating the way in which these vitamins act in the organism. It may be that development in the near future will reveal the importance for our organism of copper concerning oxidation and of vitamin C with certain followers in plants, viz. oxidating enzyme, and oxidizable and reducible substances (Szent-Györgyi's flavonoles, termed vitamin P), which are capable of forming a sensitively attuned system with the vitamin, hydrogen-superoxide and proteins, or parts of them, with active and activating sulphur in the molecule. The sulphur of the alchemists of old, out of which everything was to radiate, is destined to experience a renaissance.



Professor Albert von Szent-Györgyi. As a representative for the Caroline Institute on this occasion, I am commissioned to give expression to our high estimation of your researches.

You never swerved from your unyielding purpose to study the primary and fundamental processes of biological oxidation. Entering upon this difficult field of biochemical research you soon became a pioneer by interpreting the position and real function of co-ferment as an important link in the chain of dehydrogenating catalysts. Not even your important discoveries regarding vitamin C could deter you from following a certain strain of thought. I am deducing now from a close observation of your work that you were drawing distinctions in your mind at this occasion between your interesting discovery of ascorbic acid and the bare possibility of some other audacious plans of yours coming true. At this early stage they must have involved the investigation of the fundamental mechanism of connecting hydrogen activation with that of oxygen activation. Your intuitive mind decided in favour of the possibility of success, and you won through. In the year 1933 the first signs became visible for outsiders, and from then on the pace set by you and your co-workers at Szeged was astonishing, and your results were fundamentally new and highly important. In the midst of fervent research work with most promising aspects you are the discoverer and idealist to the mind of Alfred Nobel.

I ask you, Professor Szent-Györgyi, to receive the prize from the hands of His Majesty, our gracious King.

Darwin Still Rules, but Some Biologists Dream of a Paradigm Shift

 
That's the title of an article in today's New York times. It's written by Douglas H. Erwin, "a senior scientist at the National Museum of Natural History at the Smithsonian Institution and a research professor at the Santa Fe Institute." You can read the entire article here.

Erwin says some rather silly things about "paradigm shifts" but I'll leave that to people like John Wilkins who know what Thomas Kuhn really meant. Suffice to say, the term is very much abused these days.

Putting that aside, Erwin makes some good points about the controversies in modern evolutionary theory. He points out that most of the old "paradigm" about evolution by natural selection is being challenged in one way or another. For example,

In the past few years every element of this paradigm has been attacked. Concerns about the sources of evolutionary innovation and discoveries about how DNA evolves have led some to propose that mutations, not selection, drive much of evolution, or at least the main episodes of innovation, like the origin of major animal groups, including vertebrates.

This is correct. There's a resurgence of "mutationism" that puts more emphasis on the role of mutation in evolution. This re-emphasis is not popular among evolutionary biologists but it's gaining ground.

Comparative studies of development have illuminated how genes operate, and evolve, and this places less emphasis on the gradual accumulation of small genetic changes emphasized by the modern synthesis. Work in ecology has emphasized the role organisms play in building their own environments, and studies of the fossil record raise questions about the role of competition. The last major challenge to the modern synthesis came in the 1970s and 1980s as my paleontological colleagues, including the late Stephen Jay Gould, argued for a hierarchical view of evolution, with selection occurring at many levels, including between species.

Again, these new ideas are all in play in modern evolutionary theory. The first refers to "evo-devo" and there's no question that some evolutionary biologists are rethinking evolution in light of the discoveries in developmental biology. (I think they're wrong, but that's not the point here.)

The last item refers to punctuated equilibria and hierarchical theory. There's little doubt that Gould's ideas have shaken up the old "paradigms."

I was disappointed that Erwin omitted the biggest threat to the old view of evolution, namely random genetic drift. While we've known about drift for decades the full scale of it's role in evolution is only now beginning to be appreciated. Most people still don't realize that random genetic drift is by far the most common mechanism of evolution.

[Hat Tip: Greg Laden]

Monday's Molecule #32

 
Today's molecule is very simple. We don't need a long complicated name this time; the short common name will do. (But you're welcome to supply the IUPAC name if you know it.) The trick here is to recognize why this molecular is important and then connect it to Wednesday's Nobel Laureate(s).

Here's a hint; with hindsight, this is probably one of the most undeserving Nobel Prizes in the biological sciences.

The reward (free lunch) goes to the person who correctly identifies the molecule and the Nobel Laureate(s). Previous free lunch winners are ineligible for one month from the time they first collected the prize. There's only one (Marc) ineligible candidates for this Wednesday's reward since many recent winners haven't collected their prize. The prize is a free lunch at the Faculty Club. I've been eating there a lot recently because we've had many meeting concerning an upcoming big event at the Faculty Club on this Friday evening. (My daughter, Jane, is getting married.)

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Is antibiotic resistance evidence for Darwinian evolution?

 
Here's a short video where the IDiots discuss antibiotic resistance in bacteria. This is part of the new attack on evolution. It's the main point of Michael Behe's new book, The Edge of Evolution. The idea is that random mutation and natural selection can only break things but they can't make new structures.

I suspect that very few people can scientifically refute the arguments in this video. It can be done, but it's going to take a bit of effort.

An Interview with Michael Behe

 
I'm reading The Edge of Evolution, the new book by Michael Behe. I'm not finished but I can tell you it's going to be a challenge to refute Behe's main claims. That's not because he's correct—far from it—but because he has done a clever job of picking out scientific data to support his case. The idea is that random mutation and natural selection are simply not capable of doing the things they have to do in order for large scale changes to accumulate. His probability arguments are more sophisticated than those of the average IDiot and I think we owe it to Behe to address them rather than just dismiss them out-of-hand because we don't like the conclusion. I'm looking forward to the challenge.

Here's a short interview with Behe (#5) where he explains his views. Behe says that antibiotic resistance is an example of breaking things rather than creating new things. As you listen to him make this claim, think about the evolution of β-lactamase activity from a transpeptidase enzyme [Penicillin Resistance in Bacteria: Before 1960].


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Denyse O'Leary Asks a Question about Evolutionary Psychology

 
It never ceases to amaze me that the IDiots know so very little about the science they criticize. They have this myopic view of "Darwinism" and they refuse to adjust it no matter how many time they're told that it isn't true.

So when one of them shows the beginning of understanding, it's time to sit up and take notice. Denyse O'Leary has recently shown just a tiny glimmer on Uncommon Descent [Okay: So evolutionary biologist Larry Moran does NOT believe in evolutionary psychology].

Responding to something I wrote at the Post-Darwinist about the popularity of evlutionary psychology among atheists, Moran (a textbook co-author you may well have suffered though in school), responds:

Just for the record, Denyse, I’m one of those evil atheists that you like to rant about but I’m totally opposed to evolutionary psychology.

But you already knew that many evolutionary biologist were against evolutionary psychology, didn’t you?

No, I didn’t, Larry, and if that’s true, it’s high time more of them voiced their objections. The only sustained critiques I have seen are Hilary and Steven Rose’s unjustly neglected Alas, Poor Darwin and David Buller’s also unjustly neglected Adapting Minds. Steven Rose is a neurobiologist, but Hilary Rose is a social scientist, and David J. Buller a philosopher.

No doubt, there are many critiques out there that I haven’t seen, but I wonder what proportion comes from evolutionary biologists, as opposed to social scientists who know the difference between research and speculation.

I'm not allowed to post on Uncommon Descent—apparently they don't want to learn about evolution. I imagine that many Sandwalk readers have also been banned so here's your chance to educate Denyse.

The most prominent opponents of evolutionary psychology are Richard Lewinton, Steven Rose, and the late Stephen J. Gould. I find it hard to believe that the IDiots have never heard of Gould and aren't aware of the debate in the New York Review of Books back in the mid-90's.

Denyse, here are some recent comments about evolutionary psychology [The Central Failure of Evolutionary Psychology]. I've listed some references below.

I don't know what proportion of evolutionary biologists are opposed to evolutionary psychology but I imagine it's significant. Opposition to evolutionary psychology comes from the same people who call themselves pluralists and who don't like to be called Darwinists. (You do recall, don't you, that many evolutionary biologists have moved well beyond Darwinism? You've been told more than once.)

---

Gould, S.J. (1997) Darwinian Fundamentalism The New York Review of Books Volume 44, Number 10 · June 12, 1997

Gould, S.J. (1997) Evolution: The Pleasures of Pluralism The New York Review of Books Volume 44, Number 11 · June 26, 1997

Rose, S., Lewontin, R.C. and Kamin, L.J. (1984) Not in Our Genes. Penguin Books, New York.

John Dennehy's Citation Classic for this Week

 
Check out The Evilutionary Biologist for This Week's Citation Classic. This paper is one of the most important papers in molecular biology. For most people it was the proof that DNA is the genetic material.

Hershey, A.D. and Chase, M. (1952) Independent functions of viral protein and nucleic acid in growth of bacteriophage. J. Gen. Physiol. 36:39-56.

Sandwalk Rating

 

Toronto City Council Approves Yellow Ribbons.

 
Yesterday's report of the deaths of three Canadian soldiers in Afghanistan stampeded Toronto City Council into approving the yellow ribbon decals on fire trucks and ambulances [What Does the "Support Our Troops" Ribbon mean to You?].

The press release from City Council says it all [Statement by the City of Toronto “Support Our Troops” ribbons to remain on Fire, EMS vehicles]. There's talk on the radio that the decals will also be placed on police cars. That's insane—I hope it's a false rumour.

Toronto City Council today voted unanimously to continue the ribbon campaign on Toronto Fire and EMS vehicles for an indefinite period of time as a show of support for the Canadian Forces Personnel Support Agency.

In recommending that City Council unanimously endorse the continuation of the ribbon campaign, Mayor David Miller said that all of Canada’s men and women serving in the military have the unwavering support of all Torontonians.

Toronto’s emergency services train and work closely with the Canadian Armed Forces. They share the common thread of personal sacrifice, dedication and professionalism with Canadian forces and the two services will continue to support and work with Canada’s military.

Circular University of Toronto

 
The main front campus of the University of Toronto is a popular place these days as parades of graduating students walk across it on their way to Convocation Hall.

This photograph was taken by Sam Javanrouh at daily dose of imagery [King's College Circle]. My building (Medical Sciences Building) is at 1 o'clock. The science library is at 10 o'clock and Convocation Hall is at 3 o'clock.

Evolution Ad Wins Award

 
No, unfortunately it's not that kind of evolution. This famous commercial produced by Ogilvy & Mather of Toronto, won the Grand Prix for viral marketing at Cannes as reported in today's Toronto Star [Dove's `Evolution' ad wins at Cannes]. It may not be biological evolution but the commercial sends a powerful message anyway.