Fixing Carbon: Building a Better Rubisco

On Not Getting with the Adaptationist Program

As its complete name indicates, ribulose 1,5- bisphosphate carboxylase– oxygenase (Rubisco) catalyzes not only the carboxylation but also the oxygenation of ribulose 1,5-bisphosphate [Fixing Carbon: the Rubisco Reaction]. The two reactions are competitive—CO₂ and O₂ compete for the same active sites on the Rubisco molecule [Fixing Carbon: the Structure of Rubisco]. The oxygenation reaction produces one molecule of 3-phosphoglycerate and one molecule of 2-phosphoglycolate.

Oxygenation consumes significant amounts of ribulose 1,5- bisphosphate in vivo. Under normal growth conditions, the rate of carboxylation is only about three to four times the rate of the oxygenation reaction. The oxidative pathway consumes NADH and ATP because the products have to be converted back into ribulose 1,5- bisphosphate in order to continue carbon fixation. The light-dependent uptake of O₂ catalyzed by Rubisco, followed by the release of CO₂ during the subsequent metabolism of 2-phosphoglycolate, is called photorespiration.

The appreciable release of fixed CO₂ and the consumption of energy—with no apparent benefit to the plants—arise because of the lack of absolute substrate specificity of Rubisco. This side reaction can greatly limit crop yields. It looks very much as though Rubisco is just an inefficient enzyme that's incapable of distinguishing between two very similar substrates, CO₂ and O₂. It appears to be an example of a badly "designed" enzyme^*, not unlike many others that have significant error rates.

The inefficiency of Rubisco, both in terms or its low reaction rate and its propensity for errors, is why massive amounts of the enzyme are needed in plants. The result is that Rubisco is probably the most abundant enzyme on Earth.

But if nature has done such a bad job of design, can scientists do better? That's the goal of many research labs since improving the efficiency of Rubisco can greatly enhance crop yields, and, incidentally, makes lots of money for the inventors of the genetically modified crops.

Several labs are attempting to genetically modify plants to enhance the carboxylation reaction and suppress the oxygenation reaction. The “perfect” enzyme would have very low oxygenase activity and very efficient carboxylase activity. The kinetic parameters of the carboxylase activity of Rubisco enzymes from several species are listed in the table below (Andrews and Whitney, 2003).


The low catalytic proficiency of the enzyme is indicated by the k_cat/K_M values. These values should be compared to those of typical enzymes that have values from ten to one thousand times greater. It seems likely that the carboxylase efficiency can be improved 1000-fold by modifying the amino acid side chains in the active site.

The difficult part of the genetic modification is choosing the appropriate amino acid changes. The choice is made easier by a detailed knowledge of the structures of several Rubisco enzymes from different species and by examination of the contacts between amino acid side chains and substrate molecules. Models of the presumed transition states are also important. Additional key residues can be identified by comparing the conservation of amino acid sequences in enzymes from a wide variety of species.

The underlying strategy assumes that evolution has not yet selected for the most well–designed enzyme. This assumption seems reasonable since there are many examples of ongoing evolution in biochemistry. Nevertheless, progress has been slow in spite of the enormous financial rewards.

In addition to intelligently-directed genetic engineering to improve on nature, some groups have relied on a form of artificial evolution to do the job. Here's the abstract of a recent paper (Parikh et al. 2006).

The Calvin Cycle is the primary conduit for the fixation of carbon dioxide into the biosphere; ribulose 1,5-bisphosphate carboxylase/oxygenase (RuBisCO) catalyzes the rate-limiting fixation step. Our goal is to direct the evolution of RuBisCO variants with improved kinetic and biophysical properties. The Calvin Cycle was partially reconstructed in Escherichia coli; the engineered strain requires the Synechococcus PCC6301 RuBisCO for growth in minimal media supplemented with a pentose. We randomly mutated the gene encoding the large subunit of RuBisCO (rbcL), co-expressed the resulting library with the small subunit (rbcS) and the Synechococcus PCC7492 phosphoribulokinase (prkA), and selected hypermorphic variants. The RuBisCO variants that evolved during three rounds of random mutagenesis and selection were over-expressed, and exhibited 5-fold improvement in specific activity relative to the wild-type enzyme. These results demonstrate a new strategy for the artificial selection of RuBisCO and other non-native metabolic enzymes.

©Laurence A. Moran and Pearson Prentice Hall 2007

^*As you might imagine from our discussion of the adaptationist program, there are many biochemists who are very uncomfortable with the notion of a function that has no adaptive explanation. Textbooks are full of adaptive just-so stories that try to justify the oxygenation reaction. None of them hold up to close scrutiny. The Voet and Voet textbook (Biochemisty) avoids the worst just-so stories by saying, "Although photorespiration has no known metabolic function, the RuBisCOs from a great variety of photosynthetic organisms so far tested all exhibit oxygenase activity. Yet, over the eons, the forces of evolution must have optimized the function of this important enzyme." They then go on to describe two unlikely adaptive explanations of the oxygenation reaction. Note that Don and Judy Voet assume that the very existence of the oxygenation reaction demands an optimization assumption and, consequently, an adaptationist explanation. Accident is not a possibility in their minds.

---

Andrews, J. T. and Whitney, S. M. (2003) Manipulating ribulose bisphosphate carboxylase/oxygenase in the chloroplasts of higher plants. Arch. Biochem. Biophys. 414:159–169.

Parikh, M.R., Greene, D.N., Woods, K.K., Matsumura, I. (2006) Directed evolution of RuBisCO hypermorphs through genetic selection in engineered E.coli. Protein Eng Des Sel. 19(3):113-9.

Is There a Correct Way to Do Science?

 
I think there are incorrect ways of doing science and I think that much of today's scientific literature is an example of bad science. This isn't news. Back in 1963 Peter Medawar felt the same way and he expressed this viewpoint on a BBC radio show. The transcript, Is the scientific paper a fraud, is published in Medawar's collection of essays called "The Strange Case of the Spotted Mice" (Medawar, 1996). (The title of the book refers to a scientific fraud in immunology that Medawar uncovered in the early 1970's.)

Medawar says,

... the scientific paper may be a fraud because it misrepresents the processes of thought that accompanied or gave rise to the work that is described in the paper.

Janet Stemwedel discuses this paper on her blog Adventures in Ethics and Science [Why does Medawar hate the scientific paper?]. Janet uses the paper as a way of introducing some key concepts in epistemology—loosely defined as "the investigation of the origin, nature, methods, and limits of knowldege." (Burr and Goldinger, 1980). Read Janet's blog and the comments in order to see this perspective.

I want to take the discussion in another direction. Medawar's complaint is that the scientific paper distorts the real process of science by misrepresenting the steps that are actually followed in a scientific investigation. In particular, the typical paper suggests that induction is the main mechanism of scientific discovery. Here's how Medawar describes the naive scientific method,

What induction implies in its cruder form is roughly speaking this: scientific discovery, or the formulation of scientific theory, starts with the unvarnished and unembroidered evidence of the senses. It starts with simple observation—simple, unbiased, unprejudiced, naïve, or innocent observation—and out of this sensory evidence, embroidered in the form of simple propositions or declarations of fact, generalizations will grow up and take shape, almost as if some process of crystallization or condensation were taking place. Out of a disorderly array of facts, an orderly theory, an orderly general statement, will somehow emerge.

Now, nobody has ever accused Peter Medawar of being stupid so before you start to quibble about this sort of generalization, be aware that Medawar does not apply it to all of science and every scientific paper. He's talking about common, but not exclusive, practice.

One of the reasons why pure inductive reasoning is misleading is because we never start an investigation with a clean slate.

... the starting point of induction, naïve observation, innocent observation, is a mere philosophic fiction. There is no such thing as unprejudiced observation. Every act of observation we make is biased. What we see or otherwise sense is a function of what we have seen or sensed n the past.

This seems like something that's so obvious that it hardly deserves mentioning. But it does deserve mentioning. Medawar was right to have brought it out into the open and it's something we always need to keep in mind.

Now we get to a famous quotation from Medawar's talk. Janet Stemwedel discusses it in the context of Popper and falsification—conveniently ignoring Kuhn, who is far more relevant—but I want to use it to talk about adaptationism.

We wish to question a deeply engrained habit of thinking among students of evolution. We call it the adaptationist programme,
or the Panglossian paradigm.

Gould and Lewontin (1979)What is wrong with the traditional form of the scientific paper is simply this: that all scientific work of an experimental or exploratory character starts with some expectation about the outcome of the inquiry. This expectation one starts with, this hypothesis one formulates, provides the initiative and incentive for the inquiry and governs its actual form. It is in the light of this expectation that some observations are held relevant and others not; that some methods are chosen, others discarded; that some experiments are done rather than others. It is only in the light of this prior expectation that the activities the scientist reports in his scientific papers really have any meaning at all.

The debate between the adaptationists and the pluralists is often dismissed—usually by the adaptationists—as mere quibbling about scientific data. After all, they argue, all we need to do is collect data on each characteristic under discussion in order to resolve the question; is it an adaptation or an accident?

They are wrong. This is not a debate about facts at all. It's a debate about the the prior expectations that one has before any data is collected. Criticism of the adaptationist program focuses on the state of mind that researchers posses when they are designing experiments and formulating hypotheses to test. In other words, it's what Medawar refers to when he says that scientists start with "some expectation of the outcome of the enquiry." It's their bias or prejudice that's being questioned and not just whether the horns of an Indian rhinoceros are adaptations or not [Visible Mutations and Evolution by Natural Selection].

One of the main arguments of the Intelligent Design Creationists is that modern scientists adopt a naturalist assumption whenever they do science. This rules out creationism by definition. Some scientists attempt to deny that scientists have any pre-conceived notions at all. They promote the myth of pure inductive reasoning driven only by facts and evidence. It would be wise to drop this form of argument since it is obviously false. Scientists do have prejudices and biases. We need to recognize them and try to deal with them. The essence of skepticism is to always question your assumptions and discard them if they cease to become useful. That's what distinguishes the scientist from the preacher.

---

Burr, John, R. and Goldinger, Milton (1980) Philosophy and Contemporary Issues Macmillan Publishing Co., New York

Gould, S.J. and Lewontin, R.C. (1979) The Spandrels of San Marco and the Panglossian paradigm: a critique of the adaptationist programme. Proc. R. Soc. Lond. B 205:581-598.

P. B. Medawar (1996) "Is the Scientific Paper Fradulent?" in THE STRANGE CASE OF THE SPOTTED MICE, Oxford University Press, Oxford.

Nobel Laureate: Melvin Calvin

 
The Nobel Prize in Chemistry 1961.

"for his research on the carbon dioxide assimilation in plants"


Melvin Calvin (1911-1997) won the Nobel Prize in 1961 for his discovery of the Calvin Cycle—the pathway of carbon fixation in photosynthetic organisms, especially plants.

Calvin did most of his work with Chlorella, a green algae. The complex pathway was worked out using ¹⁴C labelled compounds to trace the various reactions inside the cell.

The presentation speech was delivered by Professor K. Myrbäck, member of the Nobel Committee for Chemistry of the Royal Swedish Academy of Sciences.

Your Majesties, Your Royal Highnesses, Ladies and Gentlemen.

In order to grow and to perform its various activities, every living organism needs a supply of energy in some suitable form. In this respect the organisms existing on this planet can be divided into two fundamentally different groups. All animals, including man, and also some lower organisms, require a supply of energy-rich organic material, food-stuffs that "contain calories", to use a popular expression. The energy contained in the food-stuffs is made available by a biological oxidation ("combustion") of carbohydrates, fats, etc. Obviously, these types of organisms, the so-called heterotrophic organisms, are absolutely dependent on supplies of organic material, occurring outside themselves.

As opposed to the heterotrophic organisms, the organisms belonging to the second group, the so-called autotrophic organisms, i.e. the green plants and certain bacteria, do not require organic material supplied from without. They synthesize organic compounds, primarily carbohydrates, from simple substances, carbon dioxide and water, substances that, in themselves, do not contain any calories. The energy needed for the synthesis is supplied by light which is absorbed by the organisms and subsequently converted by them from light energy into chemical energy. The sequence of reactions by which carbon dioxide and water are converted to carbohydrate is called carbon dioxide assimilation or, taking into account the role of light energy, photosynthesis.

It becomes obvious that photosynthesis not only provides an explanation for the existence of the autotrophic organisms but also furnishes food for man and animals. In other words, photosynthesis is the absolute prerequisite for all life on earth and the most fundamental of all biochemical reactions. It has been estimated that plants and microorganisms on earth transform about 6,000 tons of carbon from carbon dioxide to carbohydrate per second, with at least four-fifths of this amount contributed by organisms in the oceans.

It is understandable that a reaction of such importance and such dimensions should attract the interest of science at an early stage. For more than a century, however, progress in the understanding of the chemistry of photosynthesis was very slow, partly for want of suitable experimental methods.

More than fifty years ago it was recognized that photosynthesis comprised two distinct phases, light reactions and dark reactions. The Nobel Laureate today, Dr. Melvin Calvin, has spent many years of research work on the chemistry of both phases of photosynthesis and, in the case of the second phase, that is to say the reactions leading from carbon dioxide to the assimilation products - to quote Calvin, "the path of carbon in photosynthesis" his work has resulted in the complete clarification of an extremely intricate problem.

Success was achieved as a result of sharp-witted, skilful and persistent work, to some degree facilitated by the availability of certain modern experimental methods that allow investigations which, in older times, were simply impossible. Two such methods may be mentioned: the method of the isotopic labeling of molecules, introduced by de Hevesy, and the chromatographic methods, developed by Martin and Synge, which permit the separation of minute quantities of compounds in complicated mixtures. By an ingenious combination of these and many other methods, Calvin succeeded in tracking the path of the carbon atom from carbon dioxide, taken up by the plant, to the finished assimilation products. The radioactive carbon isotope, 14C well-known also in other connections, has played a particularly important role in Calvin's work.

Most of Calvin's experiments have been performed using a microscopic green alga, Chlorella pyrerloidosa, but parallel experiments with higher plants have shown that the mechanism of carbon dioxide assimilation is the same in all plants.

A question that had occupied scientists for more than a century, was: "What is the primary product of the assimilation; what first happens to the carbon dioxide taken up by the plant?" Calvin demonstrated that the primary reaction is not, as had been assumed previously, a reduction of carbon dioxide as such, but a fixation of carbon dioxide to a substance, the carbon dioxide acceptor, occurring in the plant. Calvin was able to show that the product formed in this fixation reaction is an organic compound known as phosphoglyceric acid.

This discovery was of fundamental importance for the development that followed. The primary product of assimilation was recognized as being a compound, well-known from earlier work as an intermediary product of the biological degradation of carbohydrates, and not some previously unknown compound; phosphoglyceric acid had been identified as a breakdown product of sugar as early as 1929 by Ragnar Nilsson here in Stockholm. Calvin's identification of the primary assimilation product with phosphoglyceric acid led to the very important conclusion that there is an intimate connection between photosynthesis and carbohydrate metabolism as a whole.

Calvin's subsequent investigations mapped out the path between the primary product and the end products of assimilation, the various carbohydrates.What had formerly been assumed to be a reduction of carbon dioxide was shown to be a reduction of phosphoglyceric acid. For a reduction of phosphoglyceric acid to the carbohydrate level, the plant has to supply both a reducing agent and a so-called energy-rich phosphate. It is for the production of these co-factors that plants utilize light energy. This means that light energy is not directly involved in the reactions of assimilation; light energy is used for regeneration of co-factors which are consumed in the assimilation reactions.

As mentioned above, the primary reaction in the assimilation is a fixation of carbon dioxide to an acceptor, the chemical nature of which has been established by Calvin. Rather unexpectedly, this acceptor was found to be a derivative of a sugar, ribulose, to which nobody had paid much attention previously. When carbon dioxide is fixed to the ribulose derivative, phosphoglyceric acid is formed.

As the acceptor is consumed during the fixation reaction it must obviously be regenerated from the assimilation products. Calvin has elucidated the very complicated mechanism of this regeneration. Between the primary product and the acceptor there are no less than ten intermediary products and the reactions between these products are catalyzed by eleven different enzymes.



Professor Melvin Calvin. Your investigations on plant photosynthesis have shed light on a field of biochemistry which was, until recently, veiled in obscurity. You have tracked the various steps of the path of carbon in photosynthesis and created a clear picture of this complicated sequence of reactions, reactions of immense importance for life on our planet.

On behalf of the Royal Academy of Sciences, I extend to you our warm congratulations, and I ask you to receive this year's Nobel Prize for Chemistry from the hands of His Majesty the King.

Difficult Science Question

 


I think you can figure out the question. Does this make a perpetual motion machine?

[Hat Tip: LolCat Builder via Monado]

Summer Skeptics Bash July 12 & 13th

 
Come to the Center for Inquiry, 216 Beverley Street at College, just south of the University of Toronto, in the heart of downtown.

In honour of Barry Beyerstein (1947-2007), author, Professor of Psychology at Simon Frasier University, Chair of the Society of B.C. Skeptics and Fellow of the CFI Committee for Skeptical Inquiry (formerly CSICOP).

1. FLYING SPAGHETTI MONSTER DINNER $5 (FREE for Friends of the Centre) Thurs, July 12, 7pm
   
   Featuring screening & debunking of the paranormal-plugging What the Bleep do We Know? with physics PhD candidate Edward Ackad.
   
   
2. SUPERSTITION BASH, Friday, July 13
   
   Featuring a full day of activities, including a presentation by world famous skeptical investigator Joe Nickell at 6pm and a haunted walk at 8:30pm
   
   $5 (Joe Nickell talk), $15 (Full Day, with haunted walk) - $10 full day for Friends of the Centre.

FLYING SPAGHETTI MONSTER DINNER–Thurs, July 12

Come have all the spaghetti and salad you can eat in honor of his noodly goodness. Afterwards we will be showing some great films and documentaries that will be bound to spark a great conversation.

Film: What the Bleep do we Know??

SUMMARY (from what the bleep.com):WHAT THE BLEEP DO WE KNOW?! is a new type of film. It is part documentary, part story, and part elaborate and inspiring visual effects and animations. The protagonist, Amanda, played by Marlee Matlin, finds herself in a fantastic Alice in Wonderland experience when her daily, uninspired life literally begins to unravel, revealing the uncertain world of the quantum field hidden behind what we consider to be our normal, waking reality…The chorus members act as hosts who live outside of the story, and from this Olympian view, comment on the actions of the characters below. They are also there to introduce the Great Questions framed by both science and religion, which divides the film into a series of acts. Through the course of the film, the distinction between science and religion becomes increasingly blurred, since we realize that, in essence, both science and religion describe the same phenomena.

- Featuring our "in house" physics Ph.D candidate Eddie Ackad to critically examine the documentary.

THE FRIDAY, JULY 13TH SUPERSTITION BASH

A day long event, featuring 3 components

1. The morning (9:00am - 12:30pm), with a Superstition obstacle course and related activities designed for children aged 7-9.
2. The afternoon (2:00pm - 5:00pm), with similar interactive activities designed for an older audience.
3. The evening (5:00pm - 9:30pm), with presentations and a haunted walk!

1. The morning (9:00am - 12:30pm)

• 9:00am: Introductions
• 9:15 – 10:15: Superstition Obstacle Course - 13 stations with interactive activities and educational information
• 10:15am – 10:45am: Jeopardy-style trivia game
• 10:45 – 11:00 minutes “Failed prediction listing” and snack
• 11:00 – 11:30: Fake séance (sceptics)
• 11:30 – 12:00: "Magic for sceptics", with Jennie Fiddes (see info below on this program)
• 12:00: Concluding Mirror smash, featuring Joe Nickell

2. The Afternoon (2:00pm - 5:00pm)
Similar activities as above, but with the following additional activities:

1. "Misfortune" telling
2. Homeopathic beer chugging contest
3. Voodoo Doll activity
4. Open mike setting for people to tell their own superstitions and ghost stories and for debunking opportunities
5. Evening Presentations and Events (5:00pm - 9:30pm)
• 5:00pm - 6:00pm: "Superstitions: A Critical Look" - presentation by Justin Trottier
• 6:00pm - 7:30pm: "Investigating Paranormal Claims" with Joe Nickell (see info below)
• 8:30pm: University of Toronto haunted walk, with Muddy York Walking Tours, the longest running haunted walk group in Toronto

Cost
The cost for participating in the July 13 Superstition Bash, which includes all activities, is $15. The cost for Dr. Nickell's talk only is $5. Friends of the Centre get in to all activities for $10

SPECIAL OFFER: Join now as a CFI Friend of the Centre and get into all two day Summer Skeptics Bash activities entirely free of charge!

Contact Information: Email: justin.trottier@gmail.com Phone: 416-971-5676

"Magic for Skeptics", with Jennie Fiddes

Jennie Fiddes is a recent graduate of U of T, earning a BA in Anthropology and Archaeology. She is currently employed as a field archaeologist in the GTA and is an amateur close-up magician. She recently completed an undergraduate thesis project on magic and magician culture in Toronto and is interested in all things magic related.

Jennie will be discussing why magic appeals to people and how this can be both entertaining and dangerous. By demonstrating a few tricks, she will take you through different styles of magic and show the effects they can have on the average thinker and how people can be readily fooled and the impact this can have on their emotions.

"Investigating Paranormal Claims", with Joe Nickell

As a highlight of the event, we are proud to present the world famous Dr. Joe Nickell. Joe Nickell, Ph.D., is Senior Research Fellow of the Committee for Skeptical Inquiry and investigative columnist for Skeptical Inquirer magazine. A former professional stage magician and private investigator for a world-famous detective agency, Dr. Nickell utilizes his varied background as an investigator of myths and mysteries, frauds, forgeries, and hoaxes. He has been called "the modern Sherlock Holmes," "the original ghost buster," and "the real-life Scully”. He has investigated scores of haunted-house cases, including the Amityville Horror and the Mackenzie House in Toronto, Canada.

Dr. Nickell will be discussing his long history of skeptical inquiry including investigating superstitious claims, alien encounters, haunting, and the like. Dr. Nickell stories always entertain.

The Obstacle Course

Thirteen interactive superstition stations will be setup for your enjoyment and educational enrichment:

• Station 1: The Ladder
• Station 2: Lucky Charms
• Station 3: Mirrors
• Station 4: Horseshoes
• Station 5: Black Cats
• Station 6: Cracks
• Station 7: Touch Wood
• Station 8: Four-Leaf Clover
• Station 9: Split Milk
• Station 10: The Salt Bowl
• Station 11: Pennies
• Station 12: Umbrellas
• Station 13: Hats

Fixing Carbon: the Structure of Rubisco

Rubisco (ribulose 1,5-bisphosphate carboxylase–oxygenase) is the key enzyme of the Calvin cycle. It catalyzes the fixation of atmospheric CO₂ into carbon compounds. This reaction involves the carboxylation of the five-carbon sugar ribulose 1,5 -bisphosphate by CO₂ with the eventual release of two three-carbon molecules of 3-phosphoglycerate. The reaction mechanism of Rubisco is shown in [Fixing Carbon: the Rubisco Reaction].

Rubisco makes up about 50% of the soluble protein in plant leaves making it one of the most abundant enzymes on Earth. Interestingly, its status as an abundant enzyme is due partly to the fact that it is not very efficient—the low turnover number of ~3 s^-1 (three reactions per second) means that large amounts of the enzyme are required to support CO₂ fixation!

The Rubisco of plants, algae, and cyanobacteria is composed of eight large (L) subunits and eight small (S) subunits as shown above in top (a) and side (b) views of the enzyme from spinach (Spinacia oleracea). The large subunits are shown as alternately yellow and blue and the small subunits are purple.

There are eight active sites located in the eight large subunits. Four additional small subunits are located at each end of the core formed by the large subunits. The Rubisco molecules in other photosynthetic bacteria have only the large subunits containing the active sites. For example, in the purple bacterium Rhodospirillum rubrum, Rubisco consists of a simple dimer of large subunits.

The purple bacterium version of Rubisco has a much lower affinity for than the more complex multisubunit enzymes in other species but it catalyzes the same reaction. In a spectacular demonstration of this functional similarity, tobacco plants were genetically engineered by replacing the normal plant gene with the one from the purple bacterium Rhodospirillum rubrum. The modified plants contained only the dimeric bacterial form of the enzyme. The plants grew normally and reproduced as long as they were kept in an atmosphere of high CO₂ concentration.

©Laurence A. Moran and Pearson Prentice Hall 2007

Fixing Carbon: the Rubisco Reaction

Life as we know it is based on carbon. All organisms need to have a source of carbon in order to grow and multiply. Animals, such as humans, get their carbon from eating other living things but there are many other species that can assimilate carbon directly from inorganic sources. This process is known as carbon fixation.

In most cases, carbon is derived from carbon dioxide in the atmosphere or dissolved in water. There are dozens of different chemical reactions in which carbon dioxide is taken up and attached to another organic molecule. Humans can do this to limited extent but not enough to support all of our carbon needs. Bacteria, protists, plants and fungi are much better at efficiently incorporating carbon from carbon dioxide.

The reactions of carbon fixation are often expensive because they require an input of energy to drive the assimilation of the newly-fixed carbon into metabolic pathways that are operating inside the cell. Photosynthetic organisms often have an abundant supply of energy so they can take up large amounts of carbon to make organic molecules. In fact, the association between carbon fixation and photosynthesis is so obvious that it's often assumed that the processes are directly coupled.

They aren't. There are many non-photosynthetic species that can efficiently fix carbon from carbon dioxide and there are many organisms that can carry out photosynthesis but they don't fix huge amounts of carbon using the standard pathways.

Nevertheless, there is one major carbon-fixing pathway that is present in most photosynthesizing bacteria, protists, fungi, and especially plants. It's called the Calvin Cycle after its discoverer Melvin Calvin (see photo) [Nobel Laureate 1961]. In modern biochemistry courses we discuss this pathway in the photosynthesis chapter but it's no longer considered to be part of photosynthesis. Photosynthesis ends with the light-driven synthesis of the energy molecules ATP and NADPH.

The first step in this pathway is the most important; it's the step where a carbon dioxide molecule is attached to a five carbon compound and the resulting 6-carbon intermediate is split into two 3-carbon molecules. The 3-carbon molecules then enter various metabolic pathways, including a pathway that recreates the 5-carbon precursor—hence the name "cycle."

The initial reaction is shown in the schematic below where each ball represents a carbon atom. The substrate for the reaction is the 5-carbon compound with the green balls and the blue ball represents the carbon atom in carbon dioxide (CO₂). As you can see, the reaction takes place in two steps. The first step is the actual fixation reaction; it creates a 6-carbon molecule with the incorporated carbon atom from CO₂. In the second step this 6-carbon molecule is cleaved producing two 3-carbon molecules.


The 5-carbon substrate is called ribulose 1,5-bisphosphate [Monday's Molecule #34]. It's related to the ribose in ribonucleic acid (RNA) except that it's the keto form of ribose and it has two phosphate groups attached to the 1 and 5 positions. The final products are called 3-phosphoglycerate. They are common intermediates in many metabolic pathways.

Here's the complete reaction. The enzyme that catalyzes this reaction is the most abundant enzyme on the entire planet. It's called ribulose 1,5-bisphosphate carboxylase-oxygenase, or Rubisco for short.

Mechanism of Rubisco-catalyzed carboxylation of ribulose 1,5-bisphosphate to form two molecules of 3-phosphoglycerate. A proton is abstracted from C-3 of ribulose 1,5 -bisphosphate to create a 2,3 -enediolate intermediate. The nucleophilic enediolate attacks producing 2-carboxy-3-ketoarabinitol 1,5 -bisphosphate, which is hydrated to an unstable gem diol intermediate. The C-2-C-3 bond of the intermediate is immediately cleaved, generating a carbanion and one molecule of 3-phosphoglycerate. Stereospecific protonation of the carbanion yields a second molecule of 3-phosphoglycerate. This step completes the carbon fixation stage of the Calvin cycle—two molecules of 3-phosphoglycerate are formed from CO₂ and the five-carbon sugar ribulose 1,5-bisphosphate.

©Laurence A. Moran and Pearson Prentice Hall 2007

Are IDiots Creationists?

 
I have complained about misuse of the term "Darwinism" by the Intelligent Design Creationists. They seem to be unable to grasp the fact that not all evolutionary biologists are Darwinists.

Having complained about that, it's only fair to consider their complaint that not all Intelligent Design advocates are Creationists. Casey Luskin raises the issue today on the Discovery Institute website [Another Way to Defeat the ID = Creationism MemeM].

Darwinian logic often contends that because a given proportion of ID proponents are creationists, ID must therefore be creationism. It's a twist on the genetic fallacy, one I like to call the Darwinist "Genesis Genetic Argument." As noted, it implies that each any and every argument made by a creationist must be equivalent to arguing for full-blooded creationism. This fallacious argument is easy to defeat on logical grounds by pointing out that some ID proponents are not creationists, and in fact have been persuaded to support ID in the absence of religion. Thus something other than creationism or religion must be fundamental to the set of views underlying ID (big hint: it's the scientific data indicating real design in nature)!

First off, it's ridiculous to pretend that some IDiots view the intelligent designer as anyone other than God. While I've no doubt that they might dig someone like this out of the woodwork, the fact remains that 99.999% of all intelligent design advocates see God as the designer. The term "creationist" refers to someone who postulates a role for a Creator (i.e., God) in creating life. Any IDiot who says they were persuaded to support intelligent design in the absence of belief in a Creator is, well, an idiot. But I repeat myself.

Second, there is no scientific data to indicate real design in nature. In fact, there's plenty of evidence to suggest a lack of "design" in much of nature (e.g., junk DNA). (Admittedly, many evolutionists are reluctant to accept this evidence.) The entire Intelligent Design Creationist movement is dedicated to disproving evolution. That's the extent of their "data." You don't become an Intelligent Design Creationist just because you've been brainwashed into rejecting evolution. You become an Intelligent Design Creationist because you've been brainwashed to believe in a Creator God and that, in turn, leads to the rejection of the other alternative, evolution.

There are many different kinds of creationist. They include Young Earth Creationists, Old Earth Creationists, and Theistic Evolutionists. The Theistic Evolutionists restrict the role of the Creator to setting up natural laws and then operating mostly within these natural laws to guide evolution. The Intelligent Design Creationists are a special group of creationists who argue against evolution and who claim (falsely) to have discovered evidence for supernatural creation (i.e., intelligent design). It is quite legitimate to refer to them as Intelligent Design Creationists because it distinguishes their form of creationism from the other forms of creationism.

Robert Pennock discusses this in his anthology Intelligent Design Creationism and Its Critics.

Dembski chides me for never using the term "intelligent design" without conjoining it to "creationism." He implies (though never explicitly asserts) that he and others in his movement are not creationists and that it is incorrect to discuss them in such terms, suggesting that doing so is merely a rhetorical ploy to "rally the troops." Am I (and the many others who see Dembski's movement in the same way) misrepresenting their position? The basic notion of creationism is the rejection of biological evolution in favor of special creation, where the latter is understood to be supernatural. Beyond this there is considerable variability. Some creationists think the world is young while a fewer number accept that it is ancient.

Pennock then goes on to show that Dembski is a creationist and so are most (all?) of his followers.

In spite of Luskin's whining (and Dembski's) it is quite appropriate to refer to Intelligent Design Creationism since the advocates of this superstitious nonsense are creationists by definition.

Welcome to Springfield

 
The population of Springfield has just increased by one. Meet Sandwalk. Do you see a resemblance? I don't.

Correcting the Bible

 
Read The Atheist Bible. I have a small correction to Book Two, Chapter Two which reads,

The variations in the biological organisms on Earth, described as the changes in a genetic population over time, is best explained in terms of natural selection.

The correct version should be,

The variations in the biological organisms on Earth, described as the changes in the genetics of a population over time, is best explained in terms of evolution.

Don't be shocked. This is, after all, a Bible and Bibles are notoriously inaccurate.

UPDATE: It's a miracle!!!! The atheist Bible has spontaneously mutated to a correct version of evolution. Praise the Lord.

[Hat Tip: Hemant Mehta at FriendlyAtheist.com]

Wellcome Trust Images

 
The Wellcome Trust's extensive library of images in now available through Creative Commons Licence [wellcome images].

Over on Memoirs of a Skepchick we've been challenged to find the coolest image [Something to get geeked about]. Here's my entry ....

Evolutionary Psychologists in Action

 
Alan S. Miller and Satoshi Kanazawa are evolutionary psychologists. They have written an article for Psychology Today that goes a long way toward explaining why this discipline is in such bad shape [Ten Politically Incorrect Truths About Human Nature]. Miller is a professor of social psychology in the Department of Behavioral Science at Hokkaido University, Japan. Kanazawa is a Reader in Management and Research Methodology at the London School of Economics and Political Science.

Did you know that all men prefer women with large breasts? I didn't. If true there must be a lot of very frustrated men in Asia and a lot of small-breasted spinsters wandering around somewhere. Anyway, Miller and Kanazawa have figured out why young American teenagers men like women with large breasts.

Until very recently, it was a mystery to evolutionary psychology why men prefer women with large breasts, since the size of a woman's breasts has no relationship to her ability to lactate. But Harvard anthropologist Frank Marlowe contends that larger, and hence heavier, breasts sag more conspicuously with age than do smaller breasts. Thus they make it easier for men to judge a woman's age (and her reproductive value) by sight—suggesting why men find women with large breasts more attractive.

Boy, you learn something every day from these evolutionary psychologists, don't you?

Now here's a useful bit of information. Do you know why young Muslim men are more violent and prone to suicide missions? The evolutionary psychologists have the answer,

Suicide missions are not always religiously motivated, but according to Oxford University sociologist Diego Gambetta, editor of Making Sense of Suicide Missions, when religion is involved, the attackers are always Muslim. Why? The surprising answer is that Muslim suicide bombing has nothing to do with Islam or the Quran (except for two lines). It has a lot to do with sex, or, in this case, the absence of sex.

What distinguishes Islam from other major religions is that it tolerates polygyny. By allowing some men to monopolize all women and altogether excluding many men from reproductive opportunities, polygyny creates shortages of available women. If 50 percent of men have two wives each, then the other 50 percent don't get any wives at all.

So polygyny increases competitive pressure on men, especially young men of low status. It therefore increases the likelihood that young men resort to violent means to gain access to mates. By doing so, they have little to lose and much to gain compared with men who already have wives. Across all societies, polygyny makes men violent, increasing crimes such as murder and rape, even after controlling for such obvious factors as economic development, economic inequality, population density, the level of democracy, and political factors in the region.

This is useful information. It means that we can settle all of the problems in the Middle East by withdrawing our troops and simply banning polygyny. Did somebody tell Dick Cheney?

There's lots more where this came from. Did you know that rich people have more sons than daughters? Neither did I, but lets not allow facts to interfere with a good just-so story. Here's the evolutionary explanation,

It is commonly believed that whether parents conceive a boy or a girl is up to random chance. Close, but not quite; it is largely up to chance. The normal sex ratio at birth is 105 boys for every 100 girls. But the sex ratio varies slightly in different circumstances and for different families. There are factors that subtly influence the sex of an offspring.

One of the most celebrated principles in evolutionary biology, the Trivers-Willard hypothesis, states that wealthy parents of high status have more sons, while poor parents of low status have more daughters. This is because children generally inherit the wealth and social status of their parents. Throughout history, sons from wealthy families who would themselves become wealthy could expect to have a large number of wives, mistresses and concubines, and produce dozens or hundreds of children, whereas their equally wealthy sisters can have only so many children. So natural selection designs parents to have biased sex ratio at birth depending upon their economic circumstances—more boys if they are wealthy, more girls if they are poor. (The biological mechanism by which this occurs is not yet understood.)

This hypothesis has been documented around the globe. American presidents, vice presidents, and cabinet secretaries have more sons than daughters. Poor Mukogodo herders in East Africa have more daughters than sons. Church parish records from the 17th and 18th centuries show that wealthy landowners in Leezen, Germany, had more sons than daughters, while farm laborers and tradesmen without property had more daughters than sons. In a survey of respondents from 46 nations, wealthy individuals are more likely to indicate a preference for sons if they could only have one child, whereas less wealthy individuals are more likely to indicate a preference for daughters.

If you believe this garbage then please send me an email message expressing your confidence in evolutionary psychology (and adaptationism). I'd like to talk to you about some swampland that I own in Florida. It will make a terrific vacation property.

[Hat Tip: RichardDawkins.net]

What Is Darwinism?

Over on the thread Close, but no cigar we're having a little discussion about the meaning of the term "Darwinian." I explained it as "evolution by natural selection."

Pete Dunkelberg is one of those people who emphasize natural selection in their discussion of evolution and he didn't like my description of Darwinian evolution. Pete said,

Misbegotten terminology. "darwinian processes" is creationist coinage with no meaning.

Talking of "darwinism" in biology is akin to talking of "newtonism" in physics: a bad idea. Aren't you glad physicists don't use terms like that to make polemics against each other?

wolfwalker asks: Larry, what do people mean by [these unneeded terms]? Larry tells him what Larry means. But the terms have no standard meaning. Larry's official ruling is that Darwin never heard of variable rates of morphological evolution and also thought selection was all.

It is patently untrue that the term "Darwinian" has no meaning in biology. Pete's position is that "Darwinist" refers to evolutionary biologists who no longer exist. He seems to think that everyone has become a pluralist these days. I beg to differ.

Core Darwinism, I shall suggest, is the minimal theory that evolution is guided in adaptively nonrandom directions by the nonrandom survival of small hereditary changes.... Adaptive does not imply that all evolution is adaptive, only that core Darwinism's concern is limited to the part of evolution that is.

Dawkins, R. (2003) The Devil's Chaplain p. 81 In physics, everyone knows that Newtonian physics has been extended in the twentieth century so that it's no longer accurate to refer to oneself as a Newtonian physicist since it implies ignorance of relativity. But this is a bad analogy since there are a great many evolutionary biologists (and even more of the other kinds of biologists) who are proud to call themselves Darwinists. Modern Darwinists place a great deal of emphasis on adaptation and natural selection as the main mechanisms of evolution.

Pete is dead wrong when he claims that, "Larry's official ruling is that Darwin never heard of variable rates of morphological evolution and also thought selection was all." I never said any such thing. I'm well aware of the fact that Darwin considered variable rates of natural selection and I'm well aware of the fact that he accepted other mechanisms of evolution, such as a watered down version of Lamarckism. The problem here seems to be that Pete doesn't understand the meaning of gradualism and he doesn't understand that modern Darwinists do not attribute everything in biology to selection.

As for the standard meaning of "Darwinism," Pete is correct to say that there is no universally accepted definition but that shouldn't be a surprise to anyone. There's hardly anything that all biologists can agree on.

However, there is a considerable group of evolutionary biologists who agree with Ernst Mayr when he says ...

After 1859, that is, during the first Darwinian revolution, Darwinism for almost everybody meant explaining the living world by natural processes. As we will see, during and after the evolutionary synthesis the term "Darwinism" unanimously meant adaptive evolutionary change under the influence of natural selection, and variational instead of transformational evolution. These are the only two meaningful concepts of Darwinism, the one ruling in the nineteenth century (and up to about 1930) and the other ruling in the twentieth century (a consensus having been reached during the evolutionary synthesis). Any other use of the term Darwinism by a moder author is bound to be misleading.

Mayr, E. (1991) What Is Darwinism? in One Long Argument p. 107.

See Why I'm Not a Darwinist for an earlier use of this quotation. The point is that the modern meaning of Darwinism is usually taken to mean an emphasis on natural selection.

Mayr explains the standard adaptationist view of random genetic drift by equating it with Neutral Theory and mischaracterizing the entire controversy. (This seems to be a very common trait among the defenders of strict Darwinism.)

The neutralists are reductionists, and for them the gene—more precisely the base pair—is the target of selection. Hence, any fixation of a "neutral" base pair is a case of neutral evolution. For the Darwinian evolutionists, the individual as a whole is the target of selection, and evolution takes place only if the properties of the individual change. A replacement of neutral genes is considered merely evolutionary noise and irrelevant for phenotypic evolution. (ibid p. 152)

I'm not making this up. I'm trying to do my best to represent the standard—but not universal—description of the adaptationist position. It's quite wrong for Pete Dunkelberg to pretend that the definition of Darwinism and the adaptationists is something that I created. (BTW, most pluralists treat the individual as the unit of evolution. They just believe that populations can fix alleles, even alleles with visible phenotypes, by random genetic drift as well as natural selection.)

Mayr continues,

The Darwinian wonders to what extent it is legitimate to designate as evoluton the changes in gene frequencies caused by nonselected random fixation. In some of the older (particularly nineteenth century) literature on evolution, one finds discussions on how to discriminate between evolution and mere change. There it was pointed out that the continuing changes in weather and climate, the sequences of the seasons of the year, the geomorphological changes of an eroding mountain range or a shifting river bed, and similar changes do not qualify as evolution. Interestingly, the changes in nonselected base pairs and genes are more like those nonevolutionary changes than they are like evolution. Perhaps one should not refer to non-Darwinian evolution but rather to non-Darwinian changes during evolution. (ibid p. 153)

While this position may seem extreme by 2007 standards, I believe that there are many evolutionary biologists who tend to dismiss all nonselected evolutionary change as uninteresting and unimportant. They are Darwinists. The extremists among this group attribute all kinds of things to adaptation, including most animal behavior. They are the ultra-Darwinians.

Many books have been written about the controversy in evolutionary biology between the adaptationists and the pluralists. Michael Ruse, for example, tried to explain it all last year (2006) in Darwinism and Its Discontents. Ruse is a firm believer in Darwinism, which he defines as "natural selection as the chief causal process behind all organisms." This is a common definition as explained above. However, one must read between the lines to see how Darwinists interpret that definition. A key point is what they think about random genetic drift. Here's how the Darwinist Ruse treats Sewall Wright's concept of random genetic drift.

Wright's theory is not very Darwinian. Natural selection does not play an overwhelming role. Genetic drift is a key player in Wright's world. However, although many of these ideas were taken up by later thinkers, especially by Theodosius Dobzhansky in the first edition of his influential Genetics and the Origin of Species, drift soon fell right out of fashion, thanks to discoveries that showed that many features formerly considered just random are in fact under tight control of selection (Lewontin, 1981). Today no one would want to say that drift (at the physical level) is a major direct player, although, in America particularly, there has always been a lingering fondness for it.

Michael Ruse is not an evolutionary biologist but he represents the views of Dawkins and, to a lesser extent, E.O. Wilson. They have no use for drift especially when it comes to visible characteristics. That's the hallmark of modern Darwinism.

So, is it true that no evolutionary biologist would want to say that drift is a major player in evolution? Of course not. There are lots of them who say exactly that in spite of what Michale Ruse would have you believe. Does Ruse have an answer to these "discontents?" Yes, he does ...

At the risk of damning myself in the eyes of both scholarship and God, let me be categorical. All of the critics of Darwinism are deeply mistaken,

To which I reply, you took the risk and your scholarship has been discredited. I can't speak for God.

Monday's Molecule #34

 
Today's molecule is very simple. It is well-known to all biochemistry undergraduates—or at least it was well-known at the time they wrote the exam. Let's see how many of you remember it today.

Today we need the formal IUPAC name in order to win the prize. There's an extremely obvious connection between this Monday's Molecule and Wednesday's Nobel Laureate. You will owe me a lunch if you guess the molecule correctly but can't figure out who the Nobel Prizewinner(s) is/are.

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 are no 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.

Comments will be blocked for 24 hours. Comments are now open.

Stop the Press!!! ... Genes Have Regulatory Sequences!

Ira Flatow interviews John Greally (see photo) on Science Friday. Greally talks about the ENCODE project and junk DNA. You might be surprised to learn that the expression of genes is controlled by ... wait for it ... REGULATORY SEQUENCES! According to Greally the discovery of these regulatory sequences reveals that junk DNA isn't junk at all. Greally says,

It would be a very brave person who would call it junk at this stage.

Count me as a very brave person. I claim that most of the human genome is junk and I'm not alone.

This is just one more example of the hype surrounding the ENCODE project. Read Ryan Gregory's summary at More about ENCODE from Scientific American for a good summary of what the study really says about junk DNA. The study does not say that all junk DNA has a function in spite of what you might gather from the podcast (below). The study does not say that the discovery of regulatory sequences in noncoding DNA is a breakthrough in our understanding of how genes work. In fact, as almost all of you know, the existence of regulatory sequences that control gene expression has been known for four decades. John Greally misses a good opportunity to educate the public about science and instead uses inappropriate framing to hype his own interest in gene expression. Shame.


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John Greely is the author of the News & Views article that described the original ENCODE work published in the June 14th issue of Nature. In that review he mentioned the role of regulatory sequences but focused much of his attention on the fact that large parts of the genome were transcribed. He expressed some appropriate skepticism of the results in the Nature piece but not when being interviewed on the radio. Is this appropriate? Is it what Nisbet and Mooney are talking about when they say that scientists should do a better job of framing?

[Hat Tip: Eye on DNA]