The Genome of Chlamydomonas reinhardtii

 
This week's issue of Science (Oct. 12, 2007) contains a summary of the draft genome sequence of the green alga, Chlamydomonas reinhardtii (Merchant et al. 2007) [The Chlamydomonas Genome Reveals the Evolution of Key Animal and Plant Functions].

Chlamydomonas is a single-cell green alga with a prominent chloroplast and cilia. It normally lives in the soil or in lakes and streams. Green algae are members of the division Chlorophyta, which includes all green algae. The complete genome sequencs of two other green alga, Ostreococcus tauri and Ostreococcus lucimarinus, have been published. Chlamydomonas is distantly related to Ostreococcus.

Interest in Chlamydomonas stems from the fact that it has long been a model organism and has a well-established genetic background. Furthermore, the relationship between the green algae and plants (mosses, liverworts, ferns, angiosperms etc.) is well established. The green algae share a common ancestor with all plants and this relationship is more recent than the relationship between plants and any other protists. (Red algae are the next closest group.)

The nuclear genome is 121 Mb (121,000,000 base pairs) in size and it's divided into 17 linkage groups (chromosomes). This is a draft genome sequence representing about 95% of the complete sequence with 13x coverage of the sequenced regions. The remaining 5% consists mostly of repeat regions and it's unlikely that they will ever be sequenced.

The preliminary analysis predicts 15,143 protein-encoding genes; three ribosomal RNA clusters; and 259 transfer RNA genes (tRNA). This is about the same number of genes as Drosophila melanogaster (fruit fly) but fewer than the number in mammals (~22,000). In most cases, the original estimates of gene number are inflated so we can expect this number to drop to about 12,000 as annotation continues. So far, 8631 genes have been confirmed.

There are 61 classes of simple repeat sequences; about 100 families of transposable elements; and 64 families of short interspersed elements (SINEs) that appear to be derived from tRNA genes. Most of the protein-encoding genes have introns (avg. 8 introns/gene). There are more introns and longer introns than in most unicelllar species.

Assuming 2Kb of coding region per gene, it looks like genes and their associated regulatory sequences make up about 30% of the genome. The remaining DNA (mostly junk) is evenly distributed between introns and intergenic regions.

The authors identified about 350 genes that are associated with chloroplast function. Most of these are genes that originally resided in the chloroplast DNA. Over time they have been transferred to the nucleus. These genes are easily recognized because they are related to genes from cyanobacteria, from which chloroplasts are derived, and they are only found in species that have chloroplasts.

The known genes in this group encode the proteins of the photosynthetic apparatus [A Simple Version of Photosynthesis] and the metabolic pathways found in the chloroplast (e.g., Rubisco, The Calvin Cycle). Surprisingly, over 200 of these genes have unknown functions and only half of those genes (100) belong to larger gene families from which putative functions can be surmised. This suggests that there may be some unknown pathways or functions in chloroplasts.

There are about 125 genes involved in assembly and function of the cilia (flagella) and most of these have been previously identified. Note that many different species of eukaryote contain cilia but they have been lost in plants. The only other sequenced genome from green algae is that from Ostreococcus and it's interesting to note that although Ostrecoccus does not have cilia its genome still retains half of the genes required for cilia assembly and function.

There are several other interesting features of Chlamydomonas that can now be studied with the aid of the genome sequence. For example, Chlamydomonas has a small eyespot that can detect light and trigger a phototactic response. The eyespot is related to plastids (chloroplast) except that the thylakoid membrane is packed with red pigment molecules. The specific genes involved in eyespot assembly are similar to genes found in mammalian retina and they probably interact with heme groups. The availability of a genome sequence should help to decipher the molecular architecture of this eyespot.

(The authors are from 63 different departments and institutes in the following countries: USA, France, China, Belgium, United Kingdom, Spain, Japan, Mexico, Germany, Australia, Canada, Turkey, Czech Republic, and Italy.)

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Merchant, S.S. et al. (117 authors) (2007) The Chlamydomonas Genome Reveals the Evolution of Key Animal and Plant Functions. Science 318:245-250.

[Photo Credits: The phylogenetic tree is part of Figure 2 in Merchant et al. 2007. The diagram of Chlamydomonas is from this website. It is probably taken from a textbook. The photograph of living Chlamydomonas is from this website.]

Judgment Day: Intelligent Design on Trial

 
This is a NOVA TV show about the Dover, PA trial of 2005. It sure looks interesting and I'm looking forward to seeing it on November 13th.

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[Hat Tip: Monado at Science Notes ( "Intelligent Design on Trial" - Nova, PBS TV)]

Junk RNA

There are a lot of studies suggesting that a substantial percentage of the genome is transcribed even though less than 5% is known to be functional. This leads to the idea that it encodes some unknown function. The argument is that these regions would not be transcribed unless they were doing something useful.

One objection to these studies is that the workers are looking at artifacts. The so-called transcripts are just noise from accidental transcription. This ties in with the idea that the EST database is full of examples of "transcripts" that don't make any biological sense.

There's another possibility. The regions of junk DNA could be transcribed regularly but the transcripts are rapidly degraded. They do not have a biological function. They are junk RNA.

Arthur Hunt has just posted an article on Panda's Thinb that supports this idea [Junk to the second power]. He describes the work of Wyers et al. (2005) in yeast cells. They show that there is a large class of junk RNA. The take-home lesson here is that you can't assume that some region of genomic DNA is functional just because it's transcribed. It's a lesson that many people need to keep in mind.

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Wyers, F., Rougemaille, M., Badis, G., Rousselle, J.C., Dufour, M.E., Boulay, J., Régnault, B., Devaux, F., Namane, A., Séraphin, B., Libri, D. and Jacquier A. (2005) Cryptic pol II transcripts are degraded by a nuclear quality control pathway involving a new poly(A) polymerase. Cell 121:725-37.

The 2007 Nobel Prize in Chemistry

 
The 2007 Nobel Prize in Chemistry goes to Gerhard Ertl "for his studies of chemical processes on solid surfaces." The prize is really for working out the mechanisms of catalysis on metal surfaces [Press Release].

Gerhard Ertl has founded an experimental school of thought by showing how reliable results can be attained in this difficult area of research. His insights have provided the scientific basis of modern surface chemistry: his method-ology is used in both academic research and the indust-rial development of chemical processes. The approach developed by Ertl is based not least on his studies of the Haber-Bosch process, in which nitrogen is extracted from the air for inclusion in artificial fertilizers. This reaction, which functions using an iron surface as its catalyst, has enormous economic significance because the availability of nitrogen for growing plants is often restricted. Ertl has also studied the oxidation of carbon monoxide on platinum, a reaction that takes place in the catalyst of cars to clean exhaust emissions.

It's interesting that this award comes almost 100 years after Wilhelm Oswald got the Prize for his work on catalysis in solution. See yesterday's Nobel Laureate [Nobel Laureate: Wilhelm Ostwald].

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The Difference Between Fish and Humans

 
Here's a Press Release from BBSRC [The difference between fish and humans: scientists answer century old developmental question]. What's BBSRC, you might ask? Here's the answer,

The Biotechnology and Biological Sciences Research Council is one of seven Research Councils sponsored through the UK Government’s Office of Science and Innovation and invests around £336 million per annum in the biosciences.

BBSRC sustains a world-class bioscience research community for the UK. Its mission is to fund internationally competitive research, provide training in the biosciences, foster opportunities for knowledge transfer and innovation and promote interaction with the public and other stakeholders on issues of scientific interest.

Pretty impressive, eh? With a mission like that you'd expect a world-class press release, right? Let's see how they do ...

Embryologists at UCL (University College London) have helped solve an evolutionary riddle that has been puzzling scientists for over a century. They have identified a key mechanism in the initial stages of an embryo’s development that helps differentiate more highly evolved species, including humans, from less evolved species, such as fish. The findings of the research, funded by the Biotechnology and Biological Research Council (BBSRC), were published online today by the journal Nature.

Undergraduate students in my university are taught that humans and fish share a common ancestor. They have both evolved for the same length of time from that common ancestor, therefore you cannot say that one is more evolved and one is less evolved. People who say that are demonstrating a fundamental misunderstanding of evolution.

Early on in development, the mass of undifferentiated cells that make up the embryo must take the first steps in deciding how to arrange themselves into component parts to eventually go on to form a fully developed body. This is a process known as ‘gastrulation’. During this stage, the cells group into three layers, the first is the ‘ectoderm’ which then in turn generates the ‘mesoderm’ and ‘endoderm’ layers. In higher vertebrates, such as mammals and birds, the mesoderm and endoderm are generated from an axis running through the centre of the embryo. However, in lower vertebrates, such as amphibians and fish, the two layers are generated around the edge of the embryo.

Using the terms "higher vertebrates" and "lower vertebrates" is just as bad as using "more evolved" and "less evolved."

Scientists have been speculating for over a century on the difference between the embryonic development of higher vertebrates and lower vertebrates, to help answer how the simple cell structure of an embryo goes on to form the various highly complex bodies of different species. Research leader Prof Claudio Stern explains: “This is a significant find as it is a clear difference between the embryonic development of more advanced species and less advanced species. It suggests that higher vertebrates must have developed this mechanism later on in the history of animal evolution.

Scientists who use terms like "more advanced" and "less advanced" to distinguish modern species are demonstrating their ignorance. They should not be publishing papers about evolution.

The article can be found on the Nature website [Voiculescu et al., 2007)]. Some of the authors are well-known experts with impeccable reputations in the field of development biology (e.g., Lewis Wolpert). Thus, it is surprising that the press release is so bad. What does the paper actually say?

The paper describes the process of gastrulation and formation of the primitive streak in chicken embryos. It present results that support the involvement of a particular signalling pathway in this process. The data is supported by supplemental movies [Stage XIII].

The authors go on to compare the chicken pattern of cell movement and differentiation to that in Xenopus, an amphibian. Birds and mammals are amniotes and amphibians and fish are not (= anamniotes). The paper ends with a single paragraph that mentions evolutionary implications.

We propose that local intercalation in the epiblast is responsible for positioning and shaping the primitive streak and can also explain the polonaise movements without the need for long-range gradients. Convergent extension of the axial mesoderm and neural plate in anamniotes is almost certainly conserved in amniotes, but our study reveals an additional, much earlier (pre-gastrula) cell intercalation, required for morphogenesis of the primitive streak independently of mesendoderm specification. This is apparently unique to amniotes and provides a possible answer to the classical question of how evolution converted the equatorial blastopore or shield of Anamnia into the radially oriented primitive streak of amniotes.

There's nothing wrong with this. It does not claim that amniotes are "higher" than fish or amphibians and it does not claim that fish have stopped evolving.

The disconnect between the emphasis in the paper and in the press release is disconcerting. The differences in the language used to describe evolution is very troubling. The wording of the press release perpetuates the false concept of a "ladder of life" and that's not a way to advance the education of the general public. The fact that the press release quotes the senior author making the same conceptual error suggests that the errors in the press release may not be the fault of science journalists in the media department—although in an ideal world they should have been able to correct the scientists!

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Voiculescu, O., Bertocchini, F., Wolpert, L., Keller, R.E. and Stern, C.D. (2007) The amniote primitive streak is defined by epithelial cell intercalation before gastrulation. Nature (advance online pubication: doi:10.1038/nature06211).

Ontario Votes for First-Past-thePost

 


It wasn't even close. Yesterday the voters of Ontario soundly rejected the Mixed Member Proportional voting system in favour of the status quo. I'm disappointed, but not discouraged. Next time we need to do a better job of explaining the proportional system and countering the fears and misconceptions. Given the circumstances, 38% ain't that bad. We'll try again in 2011.

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SCIENCE Questions: How and Where Did Life on Earth Arise?

 

"How and Where Did Life on Earth Arise?" is one of the top 25 questions from the 125th anniversary issue of Science magazine [Science, July 1, 2005]. The complete reference is ...

Zimmer, Carl (2005) How and Where Did Life on Earth Arise? Science 309:89. [Text] [PDF]

Carl Zimmer is one of the best science writers on the planet. He has just won the National Academies 2007 Communication Award. It goes with his many other prizes and awards. Carl has a blog [The Loom].

I've criticized many of the other articles in this series because they either misrepresented the science or blew it up out of all proportion. It should come as no surprise that Carl Zimmer's piece does not do that.

The question—how did life originate?—is without a doubt one of the top 25 questions facing us today. The subject is complex but Carl covers it in a single page without resorting to hype or misrepresentation. He mentions the fossil evidence then discusses the idea of an RNA world and how it might have formed. Then he turns his attention to the controversial field of prebiotic chemistry. Here's an example of science writing at its best.

Just where on Earth these building blocks came together as primitive life forms is a subject of debate. Starting in the 1980s, many scientists argued that life got its start in the scalding, mineral-rich waters streaming out of deep-sea hydrothermal vents. Evidence for a hot start included studies on the tree of life, which suggested that the most primitive species of microbes alive today thrive in hot water. But the hot-start hypothesis has cooled off a bit. Recent studies suggest that heat-loving microbes are not living fossils. Instead, they may have descended from less hardy species and evolved new defenses against heat. Some skeptics also wonder how delicate RNA molecules could have survived in boiling water. No single strong hypothesis has taken the hot start's place, however, although suggestions include tidal pools or oceans covered by glaciers.

Research projects now under way may shed more light on how life began.

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Theme: SCIENCE Questions

 
A few months ago I began a series of postings on the top science questions as posed by SCIENCE magazine back in 2005. The idea was to discuss the questions and also to examine how they were chosen. Are the editors of Science able to recognize the important questions in the biological sciences? So far, the results are not encouraging.

This survey was also a survey of science journalism since each of the article has been written by a different science writer. Read the postings below to get a sense of the results. There seems to be a lot of room for improvement.

May 25, 2007
Asking the Right Question

May 25, 2007
Why Do Humans Have So Few Genes?

May 25, 2007
What Is the Biological Basis of Consciousness?

May 27, 2007
To What Extend Are Genetic Variation and Personal health Linked?

May 27, 2007
How Much Can Human Life Be Extended?

May 28, 2007
What Controls Organ Regeneration?

May 28, 2007
How Can a Skin Cell Become a Nerve Cell?

June 4, 2007
How Does a Single Somatic Cell Become a Whole Plant?

June 5, 2007
What Determines Species Diversity?

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Nobel Laureate: Wilhelm Ostwald

 

The Nobel Prize in Chemistry 1909.

"in recognition of his work on catalysis and for his investigations into the fundamental principles governing chemical equilibria and rates of reaction"



Wilhelm Ostwald (1853-1932) won the Nobel Prize in Chemistry for his work on reaction rates and catalysis. His Nobel Lecture On Catalysis is one of the most fascinating and most bizarre Nobel Lectures that I have read. It's worth a look. My impression on Ostwald is that he had lost his edge and was very much aware of it. (There are references in the speech.) Does anyone know the story behind that lecture and the mysterious references?

The presentation speech provides insight into the ways scientists though about biology in those days. The idea that enzymes were catalysts was just coming into favor and it was hoped that their reactions could be followed in the same way chemical reactions were measured.

Your Majesty, Your Royal Highnesses, Ladies and Gentlemen.

The Royal Academy of Sciences has resolved to award the former professor at Leipzig University and Geheimrat, Wilhelm Ostwald, the Nobel Prize for Chemistry 1909 in recognition of his work on catalysis and associated fundamental studies on chemical equilibria and rates of reaction.

As early as the first half of last century it had in certain cases been observed that chemical reactions could be induced by substances which did not appear to participate in the reaction themselves and which at all events were not altered in any way. This led Berzelius in his famous annual reports on the progress of chemistry for 1835 to make one of his not infrequent brilliant conclusions whereby scattered observations were collated in accordance with a common criterion and new concepts were introduced in science. He termed the phenomenon catalysis. However, the catalysis concept soon came up against opposition from another eminent quarter as allegedly unfruitful and gradually fell utterly into discredit.

Some 50 years later Wilhelm Ostwald carried out a number of studies to determine the relative strength of acids and bases. He sought to solve this extraordinarily important matter for chemistry in a variety of ways which all yielded consistent results. Amongst other things he found that the rate at which different processes take place under the action of acids and bases can be used to determine the relative strengths of the latter. He performed extensive measurements along these lines, and in so doing laid the foundations for the entire procedure for studying rates of reaction, all the more essential typical cases of which he examined. From that time onwards the theory of the rate of reaction has become increasingly important for theoretical chemistry; these tests, however, were also able to throw new light on the nature of catalytic processes.

After Arrhenius had formulated his well-known theory that acids and bases in aqueous solution are separated into ions and that their strength depends on their electrical conductivity, or more accurately, on their degree of dissociation, Ostwald tested the correctness of this view by measuring the conductivity and hence the concentration of the hydrogen and hydroxyl ions with the acids and bases which he had used in his previous experiments. He found Arrhenius' theory corroborated in all of the many cases which he himself investigated. His explanation why he consistently found the same values for the relative strength of the acids and bases whichever method he used was that in all these cases the hydrogen ions of the acids and the hydroxyl ions of the bases acted catalytically and that the relative strength of the acids and bases was determined solely by their ion concentration.

Ostwald was hence led to undertake a more thorough study of catalytic phenomena and he extended its scope to other catalysts, as they were called, as well. After consistent, continuous research he successfully formulated a principle to describe the nature of catalysis which is satisfactory for the present state of knowledge, namely that catalytic action consists in the modification, by the acting substance, the catalyst, of the rate at which a chemical reaction occurs, without that substance itself being part of the end-products formed. The modification can be an increase, but also a decrease of the reaction rate. A reaction which otherwise proceeds at a slow rate, taking perhaps years before equilibrium is attained, can be accelerated by catalysts to such an extent that it is complete in a comparatively short time, in certain cases within one or a few minutes, or even in fractions of a minute, and conversely.

The rate of a reaction is a measurable parameter and hence all parameters affecting it are measurable as well. Catalysis, which formerly appeared to be a hidden secret, has thus become what is known as a kinetic problem and accessible to exact scientific study.

Ostwald's discovery has been profusely exploited. Besides Ostwald himself a large number of eminent workers have recently taken up his field of study and the work is advancing with increasing enthusiasm. The results have been truly admirable.

The significance of this new idea is best revealed by the immensely important role - first pointed out by Ostwald - of catalytic processes in all sectors of chemistry. Catalytic processes are a commonplace occurrence, especially in organic synthesis. Key sections of industry such as e.g. sulphuric acid manufacture, the basis of practically the whole chemical industry, and the manufacture of indigo which has flourished so during the last ten years, are based on the action of catalysts. A factor of perhaps even greater weight, however, is the growing realization that the enzymes, so-called, which are extremely important for the chemical processes within living organisms, act as catalysts and hence the theory of plant and animal metabolism falls essentially in the field of catalyst chemistry. As an illustration, the chemical processes involved in digestion are catalytic and can be simulated step by step using purely inorganic catalysts. Furthermore the ability of various organs to transform nutrients from the blood in such a way that they are suitable for the specific tasks of each organ can indubitably be explained by the occurrence of various kinds of enzymes within the organ capable of catalytic actions adapted to their particular purpose. That apart, it is strange that such substances as hydrocyanic acid, mercuric chloride, hydrogen sulphide and others which act as extremely potent poisons on the organism have also been observed to neutralize or "poison"even pure inorganic catalysts such as e.g. finely dispersed platinum. Even from these brief references it should be clear that a new approach to the difficult problems of physiological processes has been possible with the aid of Ostwald's theory of catalysis. Because they are related to the actions of enzymes in the living organism, the new field of research is of an importance for mankind that cannot as yet be fully gauged.

Although the Nobel Prize for Chemistry is now being awarded to Professor Ostwald in recognition of his work on catalysis, he is a man to whom the chemical world is indebted also in other ways. By the spoken and the written word he, perhaps more than any other, has carried modern theories to a rapid victory and for several decennia he played a leading part in the field of general chemistry. In other ways too he has furthered chemistry by his versatile activity with numerous discoveries and refinements in both the experimental and the theoretical spheres.

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[Photo Credit: The photograph of Ostwald's lab is from Ostwald]

The Inversion of Cane Sugar

 

Monday's Molecule #46 was the chemical reaction shown above. This is an historically important reaction that contributed to our understanding of catalysis.

The reaction shows the hydrolysis of sucrose to glucose and fructose in an acid solution. The reason why this was such an important reaction 100 years ago is because it is accompanied by a change in the direction of rotation of polarized light. Sucrose is an optically active compound, which means that it causes polarized light to rotate when you shine it through a solution of sucrose. The rotation is measured in a polarimeter. In the case of sucrose, light is rotated to the right. We call this dextrorotatory or "d" (lower case) from the latin prefix for "turning to the right". In modern chemical terminology it would be (+)-sucrose.

In the presence of acid, sucrose breaks down into D-glucose D-fructose. Both of the sugars are optically active. The "D" forms (Upper case "D" or small caps) are identified by the orientation of the CH₂OH group (red oval) in the ring structures shown above. In both cases the group is above the plane of the sugar so these are the "D" forms of the molecule. In L-glucose and L-fructose those groups would be below the plane of the sugar ring and all the -OH groups would be flipped as well.

Now here's the tricky part. The original determination of the "D" and "L" structures was related to the optical rotation properties. It was thought that all carbohydrates with the "D" configuration were dextrorotary ("d") and that's why they were named "D". The "L" forms were thought to be laevorotary (Latin: "turning to the left). However, it turns out that this assumption isn't correct and D-glucose and D-fructose are good examples. They both have the "D" configuration but D-glucose rotates the plane of polarized light slightly to the right and D-fructose rotates it strongly to the left. The way to identify this property in modern terms is D(+)-glucose and D(-)-fructose. There's a good description of these properties on the Biochemical Howlers website.

That's all very interesting but why was it important back in 1900? It was important because if you treated a solution of sucrose with acid it "inverted" polarized light from rotating to the right to rotating to the left because D-fructose affected rotation more strongly than D-glucose. This meant that you could follow the reaction in real time by carrying it out in a test tube placed in a polarimeter. This was one of the few reactions of this sort that were amenable to kinetic studies back then.

Many workers discovered that the rate of the reaction was increased by increasing acid concentrations and it led to detailed studies of reaction kinetics with large molecules. (There were plenty of inorganic reactions that could be followed by watching changes in color.) An modern example is shown in the accompanying figure from Shalaev et al. (2000).

As you can see, the kinetics of the reaction are easy to follow and the results lead to simple mathematical interpretations of the rate and extent of the reaction. It was experiments like this that led to a theory of catalysis in the early 1900's and the awarding of a Nobel Prize to Wilhelm Ostwald in 1909.

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Shalaev, E.Y., Lu, Q., Shalaeva, M. and Zografi, G. (2000) Acid-catalyzed inversion of sucrose in the amorphous state at very low levels of residual water. Pharm. Res. 17:366-70.

Tangled Bank #90

 

The latest version of the Tangled Bank has been posted on The Other 95% [Tangled Bank #90].

Democracy at Work: The Assembly's Decision

 
I'm very proud of the Ontario Citizen's Assembly on Electoral Reform. That's the group who examined many electoral systems and selected the mixed member proportional (MMP) system for Ontario. We will vote on it in a referendum tomorrow. It won't win this time around.

I think the Citizen's Assembly should be a model for many decision making processes in a democracy. In fact, I think it could be a model for grappling with complex problems in other situations as well.

Today I went to hear the President of the University brief us on long term strategic planning for the University of Toronto. I pointed out that the process was doomed from the beginning because the five major task forces were filled with appointed members of the Board of Governors and senior administrators (and former administrators). No ordinary faculty members, no students, no ordinary staff members. Nobody is going to listen to a group like that telling us what a university should be like in 20 years.

The response was that we need experienced people on these committees and that means people who have served in administrative positions in the university. I disagree. Watch this video to see another way of doing things.

Toronto Star Trashes MMP, Again

 
What in the world are they afraid of? Last week the editors of the Toronto Star came out against the mixed member proportional (MMP) system that voters will decide on in tomorrow's referendum [Electoral reform a backward step].

The editors were widely criticized for misinformation and fearmongering in that Sept. 30th editorial (e.g. The Toronto Star Endorses First-Pass-the-Post and links therein). They attacked the MMP system for giving more power to party bosses when the experience in other countries indicates that this is not a valid concern in the MMP system. Furthermore, all party leaders in Ontario are committed to a fair an open system for selecting list members. It turns out that the list will almost certainly contain only candidates who have been nominated in individual ridings.^1. Indeed, the parties have little choice but to commit to a fair and democratic process if they hope to attract voters. Read the statements of the party leaders on the Vote for MMP website [Party Leaders Quote].

Today, the editorial in the Toronto Star attacks MMP once again [Electoral reform fraught with risk]. The editors seemed to have heard part of the criticism because in this latest attack they avoid any mention of party lists. However, they return to another of the fears they raised earlier; namely, the fear of unstable government.

While some see this as a "fairer" system that produces a Legislature more closely aligned with the popular vote, it has one major drawback.

Countries that have gone this route, including Israel, Italy, Germany, and Belgium, have become notorious for chaotic, horse-trading minority governments and legislative gridlock.

Now let's think about this logically for a minute. The editors would have us believe that the Ontario Citizen's Assembly of 103 Ontario voters simply overlooked this major "problem" when they did all their research. The editors would have us believe that all 80 countries that use a proportional system have chaotic governments. Does that make sense? Of course not.

Germany, Belguim, Italy and Israel are hardly examples of failed governments in spite of what the fearmongers would have you believe. The MMP campaign refuted most of the points raised by the first Toronto Star editorial including the claim that Germany, Italy, Israel, and Belgium are in chaos because of MMP. (Belgium and Israel don't even use the MMP system.)

So why do the Toronto Star editors repeat the same false claims that were refuted 10 days ago? Why do they say the following even though they've been told that it misrepresents the experience in other countries?

Granted, some minority or coalition governments do manage to deliver solid, progressive government. But they are rarities. More commonly, governments in proportional systems are divisive, unstable, short-lived and paralyzed by conflict. Too often, the leading party is forced to align with small, sometimes radical, special-interest parties. That can badly skew the policy-making process.

Is that the kind of government that Ontario voters really want? Will it be good for Ontario? We don't think so.

Wouldn't you expect the editors to do their homework and look at the stability of comparable governments with proportional systems? Countries such as Finland, Denmark, Sweden, Norway, Switzerland, Spain, South Africa, and Austria. Is is fair to say that all these countries have governments that are "divisive, unstable, short-lived and paralyzed by conflict"? Of course not. It's a stupid thing to say. (Incidentally, all those countries use a full proportional system that's even more likely to produce "chaos" than the MMP system according to the reasoning of the fearmongers.)

In light of their previous attempts at misinformation wouldn't you expect the editors to be embarrassed? After all the Toronto Star like all newspapers prides itself on accuracy. Right?

Wrong! It's almost as though the editors have been completely oblivious to the serious attempts by the Ontario Citizen's Alliance to educate them and correct their misinformation. They repeat the same flawed argument they made ten days ago.

When people spread misinformation and fear for the first time you can put it down to ignorance. When they do it a second time there's something more serious going on. Why do the Toronto Star editors fear MMP so much that they have to publish an editorial the day before the vote? This is really strange given that all the polls show that MMP will be soundly defeated tomorrow.

It's a difficult question. As far as I can tell, the main problem is the fear of minority viewpoints—or "fringe" parties as the editors prefer. The editors are comfortable with the present first-past-the-post (FPTP) system because they know that minorities in our society have no chance of being represented in the legislature under that system.

Take the Green Party for example. Under FPTP their chances of electing a member to parliament are close to zero. Under MMP they will get four seats (out 0f 129) if 3% of the population votes for them. (The Green Party is the only "small, sometimes radical, special-interest" party that has a decent chance of electing members.)

This could lead to chaos if you believe the editors because parties with less than a majority of seats would have to negotiate with the other parties in order to get legislation passed—just like the current federal government under Harper and the previous one under Martin. Is that the "chaos" that the Toronto Star fears?

I don't think the editors and their allies are afraid of minority governments so much as they're afraid of giving minority citizens a voice in parliament. In other words, what they really want is a system that blocks out the views of minority groups. That's exactly the flaw that MMP is designed to overcome. It would be more honest if the opponents of MMP would simply come right out and what they're really afraid of instead of making up stories about unstable governments in countries with proportional voting.

Perhaps we could reach a compromise? We could have a mixed member proportional system but then ban all those parties we don't like? The editors and other concerned citizens could draw up a list of minority groups who would be specifically excluded from parliament, like the environmentalist extremists. The sitting members of Parliament would then pass a law preventing these undesirable parties from running candidates in the next election. That way we could have the best of both worlds, a proportional system that excludes all those undesirable minorities who might cause chaos if we let them have a voice in Parliament. That's how democracy is supposed to work, isn't it?

Do you think the fearmongers would go for this? I doubt it, it makes their motive a little too obvious. It's so much better to hide behind the unfair FPTP system on the grounds that it produces "stable" government. Those of you who laughed at this video should watch it again now that the anti-MMP side has triumphed. It pretty much sums up the logic of their arguments.

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1. The reason why the list will contain candidates who have been nominated in ridings—and who will run in those ridings—is because if a party wins an election they will not have any members chosen from the list. Thus, a party who hopes to win would be foolish to put candidates on the list who they want to be in parliament but who don't seek election in a constituency. Since no party will want to be seen to anticipate losing it will probably be standard practice to put people on the list who are running for election in a riding. Thus, the MMP system will end up being similar to FPTP and fears about party bosses choosing favorites are unfounded.

Vanity License Plates

 

Karl Mogel at The Inoculated mind is looking for science-related vanity license plates [My new license plate].

Here's one; it's from my fellow biochemistry Professor Peter Lewis. Peter is also Vice-Dean, Research and International Relations in the Faculty of Medicine.

This Is a Joke, Right?

 
According to several sources, this add is being shown on television in the USA and it's sponsored by the US government. I hope this is an elaborate leg-pulling. Surely there are no rational adults who think that telling kids not to have sex is going to work? I'm even surprised that there might be adults who think it's a good idea. Haven't they heard? Sex is fun and healthy.

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[Hat Tip: Greg Laden: Wait ’till you’re married to have sex]

Tagged by the Evolution Meme

 
Shalini at Scientia Natura has tagged me with the evolution meme [ I've been tagged!]. The idea is to pick five postings that show the evolution of Sandwalk from the time it first started until now.

This is going to be hard since my blog is less than one year old. Starting in the very first week I published an article on the sea urchin genome [Sea Urchin Genome Sequenced and I've continued to post science articles all along. The biggest change occurred in January when I started combining Monday's Molecule with Wednesday's Nobel Laureates to develop themes for the week. Gradually these themes spread over into following weeks (e.g. Blood Clotting). They began to take over my life!

My postings about atheism and religion haven't changed very much over the past year so there doesn't seem to be any evolution there. Many people will be upset by that since they would very much like to have changed my opinion! My interest in the influence of atheism and the confrontation with the "appeasers" was there from the very first weeks. The thing that's changed is that I now avoid the word "appeasers" and "Neville Chamberlain" whenever possible [The Neville Chamberlain Atheists].

When I started Sandwalk I blogged about Canada and local politics but not very often [I'm Voting for Hurricane Hazel!]. I thought I should avoid being seen as too Canadian because it would scare off readers, especially Americans. Now I'm posting more on Canadian issues because there's a large Canadian audience out there and because non-Canadians don't seem to mind—some even find it interesting [MMP: Debunking the Myths, Chastising the Fearmongers].

The biggest change has been the number of people who comment on Sandwalk. In my opinion, some of the most interesting things on this blog are taking place in the debates and discussions that occur after an initial posting [Plants, not Fungi, Are Most Closely Related to Animals?]. This was one of the things I wanted to happen since I'm coming from a newsgroup background but it didn't happen for the first six months. I realize now that you need a critical mass of readers in order to get a discussion going.

I tag:

easternblot
Primordial Blog
Runesmith's Canadian Content
Genomicron [which has definitely evolved]
Sex, Genes & Evolution [which hasn't?]
Thoughts in a Haystack [which should :-)]

Monday's Molecule #46

Today's molecule is actually three molecules. You have to identify each one precisely by giving the complete IUPAC names.

There's an indirect direct connection between the reaction shown above and Wednesday's Nobel Laureate(s). See if you can guess the Nobel Laureate. This one is not easy.

The reward goes to the person who correctly identifies the molecules and the Nobel Laureate(s). Previous free lunch winners are ineligible for one month from the time they first collected the prize. There are two ineligible candidates for this Wednesday's reward. The prize is a free lunch at the Faculty Club.

Send your guess to Sandwalk (sandwalk(at)bioinfo.med.utoronto.ca) and I'll pick the first email message that correctly identifies the molecule and the Nobel Laureate(s). Correct responses will be posted tomorrow along with the time that the message was received on my server. This way I may select multiple winners if several people get it right.

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

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Note: The reaction shown above may not be entirely accurate. If you can identify a way to improve it you can double your prize to two free lunches anywhere within two blocks of the downtown campus!

The 2007 Nobel Prize in Physiology or Medicine

 
The winners of the 2007 Nobel Prize in Physiology or Medicine were just announced this morning. This year's prize goes to Mario R. Capecchi, Martin J. Evans and Oliver Smithies for their work on "principles for introducing specific gene modifications in mice by the use of embryonic stem cells."

This is a bit of a surprise. These were not names that came up regularly in Nobel Prize Gossip. Many people, including me, thought that there would be a specific award for stem cells before anyone got the prize for exploiting stem cells. This doesn't mean that todays winners aren't worthy. I doubt that anyone will question the award to Oliver Smithies, for example. I don't know as much about Capecchi and Evans.

See Press release for a complete description of the work of Capecchi, Evans, and Smithies. Here's the summary ...

This year's Nobel Laureates have made a series of ground-breaking discoveries concerning embryonic stem cells and DNA recombination in mammals. Their discoveries led to the creation of an immensely powerful technology referred to as gene targeting in mice. It is now being applied to virtually all areas of biomedicine – from basic research to the development of new therapies.

Gene targeting is often used to inactivate single genes. Such gene "knockout" experiments have elucidated the roles of numerous genes in embryonic development, adult physiology, aging and disease. To date, more than ten thousand mouse genes (approximately half of the genes in the mammalian genome) have been knocked out. Ongoing international efforts will make "knockout mice" for all genes available within the near future.

With gene targeting it is now possible to produce almost any type of DNA modification in the mouse genome, allowing scientists to establish the roles of individual genes in health and disease. Gene targeting has already produced more than five hundred different mouse models of human disorders, including cardiovascular and neuro-degenerative diseases, diabetes and cancer.

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[Photo Credit: GETTY, Time magazine]

Junk in your Genome: LINEs

Scientists first began to get a glimpse of the organization of mammalian genomes about 40 years ago when they looked at the overall complexity using hydridization technology. It soon became apparent that most of the genome was made up of short stretches of DNA that were repeated thousands of times. One major component of this repetitive DNA was about 6000 bp in length. These sequences were called Long Interspersed Elements or LINEs. The other component was much shorter, about 300 bp. These were called Short Interspersed Elements or SINEs.

We now know that LINEs are a form of retrotransposon. The major human LINE is called L1 and it has two open reading frames (ORF's) that are similar to the gag and pol genes of typical retrotransposons [Retrotransposons].


The LINE sequence (blue, above) is organized like a typical gene with a 5′ untranslated region (5′ UTR) and a 3′ untranslated region (3′ UTR). There are two open reading frames (ORF) encoding an RNA binding protein, a reverse transcriptase, and an endonuclease similar to the retrovirus integrase. Like most transposons, L1 is flanked by a short repeated section of genomic DNA.

The role of the RNA binding protein has not been fully worked out but the roles of the reverse transcriptase and endonuclease proteins are known. When the L1 sequences is transcribed, it can be copied into double-stranded DNA and this copy can be integrated into the genome at a site cleaved by the endonuclease.

The copy-integration scheme is shown in the figure on the left from Current Genetics: junk DNA - repetitive sequences.

The net effect of this mechanism is to spread a copy of L1 to another part of the genome. Thus, L1 is a typical selfish DNA transposon.

The human genome contains about 500,000 copies of L1 but the vast majority are fragments of various sizes. Most of the fragments are missing the 5′ end and they presumably arose when the copying mechanism failed to completely copy the L1 mRNA from the 3′ end. About 10,000 copies are full length (6000 bp) and of these 80-100 are known to be "active." Active L1s have intact ORFs and they are regularly transcribed.

About 17% of your genome is composed of L1 LINEs and fragments. It is one of the major sources of junk DNA in your genome.

The important point to remember is that the active L1 LINEs are constantly producing reverse transcriptase in human cells. This enzyme can copy any available RNA into double-stranded DNA. It is responsible for most of the pseudogenes that litter our genome contributing to the mass of functionless DNA known as junk.

Atheists Spreading the Word

 
On Friday evening there was a 20 minute segment about atheism on CBC's The National. The National is the main evening news program on CBC. The segment is broken up into three YouTube videos (below).

I think it's a pretty good introduction to atheism and I can't imagine that it would have made the evening news a few years ago. No matter what anyone says, the evidence that Dawkins, Harris, et al. have moved this debate into the public realm seems overwhelming. I just don't understand those who think that the "militant" atheists are hurting the cause.

Look for Justin Trottier of the Centre for Inquiry. He's at the beginning of the third video. If you live in Toronto you should come out to our meetings at the centre [Standing Room Only]. It's just a block south of the campus. If you're a student you should join the University of Toronto Secular Alliance. We have many exciting events planned for this year. Watch for "Café Inquiry" coming this winter.

Tea might pose fluoride risk

 
Here's an example of bad science journalism from the latest edition of New Scientist [Tea might pose fluoride risk].

Tea might pose fluoride risk

Tea drinkers beware. Too much of the wrong kind can add significantly to the amount of fluoride you consume, with the tea in just four cups supplying up to one-third of the maximum safe daily amount.

You have to read further in the article to see that it refers to a study done in Sri Lanka where the drinking water contains high levels of fluoride.

In some parts of Sri Lanka drinking water contains up to five times the maximum fluoride recommended by the World Health Organization, and some 98 per cent of people are affected by fluorosis.

The study shows that local tea grown in Sri Lanka contains fluoride so when you make tea with the water containing excess fluoride you get an increased dose of fluoride. Even if you make the local tea with distilled water you still get excessive doses of fluoride with just four cups of this tea.

All this is explained in the article but the headline and the opening paragraph are very misleading. It's only certain kinds of tea that might cause a problem and it's not at all clear whether people in other countries can even buy this tea. It almost seems as though the person who wrote this article was deliberately trying to to scare people in order to attract readers. That's not acceptable science journalism.

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[Photo Credit: Harvesting tea leaves in Malaysia from Encyclopedia Brintannica]

Psychic Arrested in Calgary

 
A psychic who defrauded someone of $220,000 US ($218,000 CDN) was recently arrested in Calgary. I'm not going to give you the details. You'll have to hop on over to Mike's Weekly Skeptic Rant to find out.

Fortunately, Mike makes it a bit easy to guess the right answer when he proposes this multiple choice question.

So there's this "psychic" who reads palms, gives advice, sees the future; she is on the run from police. The cops are hot on her trail. Does she:

a) use her psychic powers to see where the cops are and how they'll approach?

b) influence the "universe" by putting her desires out there to be realized?

c) go downstairs and sit at the kitchen table with a delicious Hot Pocket and a pistol to await her bullet-ridden showdown with Johnny Lawdog? or

d) realize that her "powers" are non-existent and hide in the closet under some blankets?

Mike also has a useful suggestion for what to do with all the money, assuming it's recovered. Should it all be returned to the "victim"?

Gene Genie #17

 

The 17th edition of Gene Genie has just been published on Gene Sherpas [Gene Genie #17 and 10,000 visitors].

If you don't know about Gene Sherpas then this is your chance to check it out. The blog is run by Steve Murphy, a physician with a very special interest.

I am the founder of a Personalized Medicine practice (likely the first private practice of its kind). In addition I am the Clinical Genetics Fellow at Yale University until 2010. Now not under contract and that's why I am posting and running my practice. I also am developing a modern medical genetics curriculum for residents and other physicians. On this blog I am educating the public and hopefully some physicians about the field of genetics and personalized medicine.

A former student of mine shares these interests. He tells me that physicians don't get much education in genetics while in medical school and as a result they aren't up to speed when it comes to understanding the genetics of various diseases.

Another former student of mine is a genetic counselor. This is a growing field of professionals who can advise patients (and doctors) about human genetics.

Linnaeus 2007

 
This year marks the 300th anniversary of the birth of Carl Linnaeus. There will be celebrations all around the would but Sweden is leading the way [Linnaeus 2007].

Linnaeus' Life and Achievements

Carl Linnaeus is the most well-known Swedish scientist, both internationally and in Sweden. He has left traces in many ways: there are places that bear his name, there are locations on the Moon that have been named after him, he is depicted on Swedish banknotes, and "Linnea" is a popular first name for girls in Sweden. Carl Linnaeus placed his stamp on a complete era of scientific history - the Linnaean era. The Linnaean era is characterised by an ambition to catalogue, organise and give names to the whole natural world.

Mapping Nature

Linnaeus is probably best known as a botanist, and for his sexual system. His scientific achievements, however, also extend into the mineral world and zoology, in addition to botany. He was curious about the complete natural world, and wanted to map the whole of nature. This mapping has given us the naming convention known as the "binary nomenclature", that Linnaeus introduced. Linnaeus published a number of rule-books on which the system was based, and the system, after some initial resistance, has come not only to dominate natural history, but also to influence other scientific fields. Linnaeus clarifies language, he bases his science on a rigid terminology, formulates the concept of species and sets the broad dimensions of natural history. Humans in his system, for example, are known as Homo sapiens and they are primates in the class of mammals, Mammalia, - all of these are names and concepts that Linnaeus coined.

The Linnaean Conceptual Structure

The Linnaean conceptual structure has become popular both within the academic world and among hobbyists. The concept has spread throughout the world, initially by those known as the "Linnaean apostles", a group of disciples who reached farther afield throughout the world than any Swedes had previously reached. Their deaths in far-flung places carry a hint of heroism, they died for the sake of science. The continued influence of Linnaeus has stimulated scientific journeys, cataloguing and strange destinies, but it has also had a more calm interaction with nature at many places across the globe, with its placid nature of collection and systematic thought. Linnaeus creativity and sense of curiosity has left traces not only in science but also in literature and in other fields of culture.

Skagit Valley Provincial Park

 
Today's Botany Photo of the Day is a picture of the forest in Skagit Valley Provincial Park in Southern British Columbia on the USA border.

The little thumbnail on the left doesn't do justice to the photograph. You need to see the whole thing. Isn't it beautiful?

The Spandrels of San Marco and the Panglossian Paradigm

This week's citation classic on The Evilutionary Biologist is "The Spandrels of San Marco and the Panglossian Paradigm: A Critique of the Adaptationist Programme" by S.J. Gould and R.C. Lewontin [This Week's Citation Classic].

This is John Dennehy's best choice by far. It's a classic paper and everyone interested in evolution must read it carefully. Whether you agree with Gould & Lewontin or not, you can't participate in the debate unless you've read and understand this paper. I'm pleased that John appreciates it, although I'm a little upset over some of the things he says about Gould. Clearly, he needs some remedial indoctrination re-education ....

[There's a link to an online version of the paper from John's article so nobody has any excuse not to read it.]

Are You as Smart as a Third Year University Student? Q5

 
Question 1
Question 2
Question 3
Question 4
The standard Gibbs free energy change for the aldolase reaction in the direction of cleavage is +28 kJ mol-1. What does this tell you about the properties of this reaction in yeast cells that are actively producing ATP via glycolysis?

         a)  flux through this particular reaction will be
                in the direction of gluconeogenesis
         b)  the activity of this enzyme must be regulated
         c)  there must be another enzyme in yeast that bypasses this reaction
         d)  this is the rate limiting reaction in glycolysis
         e)  the concentration of FBP will be very much higher than
                the concentration of G3P

Are You as Smart as a Third Year University Student? Q4

 
Question 1
Question 2
Question 3The open-chain form of fructose 1,6-bisphosphate is shown as the substrate for the aldolase reaction. Why?

         a)  the open-chain form is more abundant inside the cell
         b)  cyclic molecules destabilize the transition state
         c)  the product of the previous reaction in glycolysis
               is the open-chain form
         d)  the open-chain form is thermodynamically more stable
               and this contributes to the positive standard Gibbs free
               change for the reaction
         e)  the active site of the enzyme can’t accommodate the
                furanose or pyranose forms

The Aldolase Reaction and the Steady State

 
On banning the word "spontaneous" to describe biochemical reactions.Aldolase is an enzyme that's important in gluconeogenesis and glycolysis. I'm discussing it because RPM is describing his work on aldolase genes in Drosophila melanogaster [Aldolase in Gluconeogenesis & Glycolysis].

Fructose 1,6-bisphosphate aldolase ("aldolase") catalyzes the reaction shown below where two 3-carbon compounds are joined to produce a 6-carbon fructose molecule.


The mechanism of aldolase is described in Pushing Electrons. What I want to discuss here is the fact that this reaction is reversible. It has to operate equally efficiently in either direction.

The direction shown is part of gluconeogenesis: the synthesis of glucose. The standard Gibbs free energy change for this reaction is -28 kJ mol^-1 (ΔG°′ = -28 kJ mol^-1). This may not mean a lot to most of you but it indicates that under standard conditions the reaction gives off a lot of energy. Very negative values are associated with release of energy and energy release is favored over uptake of energy.

In terms of old fashioned biochemistry, we would have said that the reaction was spontaneous in the direction shown. In other words, the enzyme will be more likely to synthesize fructose 1,6-bisphosphate (F1,6P) than to break it down.

This perspective is very misleading since inside the cell the reaction can easily flow in either direction depending only on small changes in the concentrations of substrates and products. In the new way of looking at metabolism we no longer talk about reactions being spontaneous and we no longer use the standard Gibbs free energy changes (ΔG°′) as indicators of direction. This change in teaching was stimulated, in part, by the difficulties in explaining how the aldolase reaction could catalyze breakdown of fructose 1,6-bisphosphate to dihydroxyacetone (DAP) phosphate and glyceraldehyde 3-phosphate (G3P) in the face of a standard Gibbs free energy change that was very positive. (The value for the reverse reaction is +28 kJ mol^-1.) Those kind of reactions weren't supposed to happen in the old textbooks and it suggested that glycolysis is impossible.

Here's how we think about it today. What the standard Gibbs free energy change tells us is that under standard conditions the reaction will proceed to the right until equilibrium is reached. The standard conditions are 1M concentrations of all the substrates and products.

When enough of the substrates are converted to product the reaction will start to flow in the opposite direction until eventually an equilibrium is reached where the rate of synthesis of fructose 1,6-bisphosphate equals the rate of its breakdown. At this point the real (as opposed to standard) Gibbs free energy change will be 0 (zero). There will be no overall tendency for the reaction to flow in one direction or the other. The concentrations of substrates and products at this point will be the equilibrium values. I hope it's clear that at equilibrium the concentration of fructose 1,6-bisphosphate will be much higher than the concentrations of dihydroxyacetone and glyceraldehyde 3-phosphate. We can illustrate this in a cartoon that represents the concentrations as blobs of various sizes.


The standard Gibbs free energy change doesn't tell us whether a reaction will be spontaneous or not. Instead, it simply tells us the final concentrations of substrates and products at equilibrium. (You can calculate this using simple equations that you learn in introductory chemistry courses.) The equilibrium concentrations are the concentrations found inside the cell since almost all reactions operate at Gibbs free energy values close to zero. In other words, most biochemical reactions are near-equilibrium reactions with steady-state concentrations close to the equilibrium values.

The concentrations of the substrates and product of the aldolae reaction look like the blob cartoon shown above. If the cell is making glucose then there will be a steady trickle of substrates flowing into the reaction and this increases the substrate concentration (little blobs) a little bit so that more of it is converted to fructose 1,6-bisphosphate (F1,6P) (big blob) in order to restore the equilibrium.

Conversely, if the cell is breaking down glucose then the concentration of fructose 1,6bisphosphate will increase above the equilibrium, steady-state value and more of it will be broken down to the 3-carbon compounds. This will happen in spite of the fact that there is already a lot more F1,6-P inside the cell than G3P and DAP.

This explains why the central reactions of the gluconeogenesis/glycolysis pathways can catalyze reactions in either direction and can swich quickly from one direction to another. The key is that the steady-state concentrations inside the cell are far from the standard concentrations.

Aldolase in Gluconeogenesis & Glycolysis

RPM at evolgen has started a series of articles on publishing original research on blogs. He's going to tell us about the aldolase genes in Drosophila melangogaster. I'm sure he's going to be explaining some interesting studies about the evolution of the two aldolase genes so I urge you to pay attention. Here are the three postings so far.

Publishing Original Research on Blogs - Part 1
Publishing Original Research on Blogs - Part 2
Publishing Original Research on Blogs - Part 3

I hope he won't mind if I describe some of the biochemistry of the aldolase catalyzed reaction and the pathways where aldolase is involved. I don't think RPM is going to do any more than what he briefly described in Part 2.

The first point I want to make is that aldolase is a type of enzyme that forms and cleaves carbon-carbon bonds. There are many different types of aldolases with different substrates and products. The most common of these enzymes is fructose 1,6-bisphosphate aldolase. Because it's so common it is often just called "aldolase." All of the the other aldolases must be specified in order to avoid confusion.


There are two different kinds of aldolases (i.e., the fructose 1,6-bisphosphate kinds). Class I enzymes (left, above) are only found in plants and animals. Class II enzymes (right, above) are usually found in bacteria, protists, and fungi. Many species of plants and animals have both types of enzyme. The two different types of aldolase are completely unrelated. They have different structures and sequences even though they catalyze the same reaction. I think the two Drosophila aldolase genes that RPM is discussing both encode Class I aldolases.

Aldolase is one of the most important enzymes in the pathway known as gluconeogenesis (glucose biosynthesis). In this pathway two molecules of the 3-carbon compound pyruvate [Pyruvate] are eventually converted to one molecule of the 6-carbon compound glucose. The gluconeogenesis pathway reads from bottom to top in the figure on the left.

One of the key steps in this pathway is the joining of two 3-carbon molecules to make a single 6-carbon molecule. That's the step catalyzed by aldolase. The substrates are glyceraldehyde 3-phosphate and dihydroxyacetone phosphate and the product is fructose 1,6-bisphosphate.

All species can synthesize glucose 6-phosphate using this pathway. It is clearly one of the most ancient pathways in cells. Early on in the history of life—once glucose molecules began to accumulate in the biosphere—there was a need to convert them back to pyruvate and recover the energy that had been used to synthesize glucose in the first place. In most species this pathway was the Entner-Douderoff pathway, a pathway related to the pentose phosphate pathway. It involves another type of aldolase called KDPG aldolase that joins glyceraldehyde 3-phosphate directly to pyruvate.

Somewhat later, new enzymes arose that could get around the difficult steps in gluconeogeneis. These are shown as separated red arrows in the figure. This new pathway is called glycolysis and it represents a more direct "reversal" of gluconeogenesis. All eukaryotes, and most bacteria have the glycolysis pathway. They are capable of converting glucose to pyruvate using a few specialized enzymes and most of the same enzymes used in gluconeogenesis. Notice that the enzymes, substrates and products of the core part of the pathway (from fructose 1,6-bisphosphate to phosphoenolpyruvate) are identical in glycolysis and gluconeogenesis (parallel red and blue arrows). What this means is that flux in this part of the pathway can flow in either direction depending on the state of the cell. This includes the aldolase reaction.

Gluconeogenesis is usually more important than glycolysis. In order to appreciate this, think about plants. They make all of their glucose from carbon dioxide so the only glucose that can be broken down is the glucose that the plants make themselves. It follows that more glucose is synthesized than is broken down by glycolysis. This is true of bacteria, protists and fungi.

The situation in animals is a little different since glucose is an important food source. It's possible that the overall flux in this pathway favors glucose breakdown although even in animals there is considerable glucose synthesis going on.

The bottom line is that aldolase is mainly required for gluconeogenesis and only in animals, and some specialized species (like yeast), is glycolysis more important. In older biochemistry textbooks the emphasis was on glycolysis and not gluconeogenesis. This is because the more classical biochemistry tended to focus on mammalian fuel metabolism (rat liver biochemistry) where glycolysis was important and glucoenogenesis was not. The mammal-centric form of teaching ignored the evolutionary history of metabolism and it's importance in other species.

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[Figure credits: The structure of the class I aldolase is from PDB 2ALD. The class II structure is from PDB 1ZEN]

Norway Is Not a Christian Nation

 
Recent poll results for Norway give this breakdown when it comes to religious beliefs.

• 29 percent believe in a god or deity
• 23 percent believe in a higher power without being certain of what
• 26 percent don't believe in God or higher powers
• 22 percent have doubts

No matter how you slice it, Norway is not a Christian nation.

So, how does this lack of firm religious belief translate into Norwegian society? Are Norwegians immoral, warmongering, and poverty-stricken? Here's a letter to the Montgomery Advertiser that answers that question [Norway flourishes as secular nation].

And what has secularism done to Norway? The Global Peace Index rates Norway the most peaceful country in the world. The Human Development Index, a comparative measure of life expectancy, literacy, education and standard of living, has ranked Norway No. 1 every year for the last five years.

Norway has the second highest GDP per capita in the world, an unemployment rate below 2 percent, and average hourly wages among the world's highest.

Hmmm ... now that can't be right, can it?

How does secular Norway stack up against true Christian nations like the USA and South Africa?

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[Hat Tip: RichardDawkins.net]