Nobel Laureates: Deisenhofer, Huber, and Michel

 
The Nobel Prize in Chemistry 1988.

"for the determination of the three-dimensional structure of a photosynthetic reaction centre"

Johann Deisenhofer, Robert Huber, and Hartmut Michel received the Nobel Prize in 1988 for working out the structure of the first photosystem—the photosynthetic reaction centre from the purple bacterium Rhodopseudomonas viridis. We now know that this is a Photosystem II-type complex with a type II reaction center. Its chlorophyll molecules absorb a photon of light and catalyze the transfer of electrons from an electron donor (usually cytochrome c) to quinone.

The photosystem structure was one of the most complex structures ever solved by X-ray crystallography. Even today there are only a handful of solved structures that are as complicated as this one.

The complex is normally embedded in a lipid bilayer that surrounds the vertical α-helices shown in the figure. The large gray space-filling molecules in the middle are the chlorophyll molecules that absorb light. Excited electrons are released from the chlorophylls and transferred down toward the bottom of the molecule to reduce a bound quinone near the iron atom (brown dot).

The cytoplasm on the inside of the cell is at the bottom of this picture and the intermembrane space between the inner and outer bacterial membranes is at the top.

The reaction center chlorophylls need to be resupplied with electrons and these come from a type c-like cytochrome (purple) that's attached to the top of the photosystem. This particular cytochrome is unusual since it has multiple heme groups. In most other species the electron donor is cytochrome c.

As noted in the presentation speech, by solving the structure of a bacterial photosystem Deisenhofer, Huber, and Michel not only contributed to our understanding of photosynthesis but also to our understanding of all membrane proteins and of electron transfer reactions in general.

The structural determination awarded has led to a giant leap in our understanding of fundamental reactions in photosynthesis, the most important chemical reaction in the biosphere of our earth. But it has also consequences far outside the field of photosynthesis research. Not only photosynthesis and respiration are associated with membrane-bound proteins but also many other central biological functions, e. g. the transport of nutrients into cells, hormone action or nerve impulses. Proteins participating in these processes must span biological membranes, and the structure of the reaction center has delineated the structural principles for such proteins. Michel's methodological contribution has, in addition, the consequence that there is now hope that we can determine detailed structures also for many other membrane proteins. Not least important is the fact that the reaction center structure has given theoretical chemists an indispensable tool in their efforts to understand how biologic electron transfer over very large distances on a molecular scale can occur as rapidly as in one billionth (American English, trillionth) of a second. In a longer perspective it is possible that such research can lead to important energy technology in the form of artificial photosynthesis.

Poor IDiots, Wrong Again

 
GilDodgen over at Uncommon Descent has put his foot in it once again. This time the IDiots have jumped all over the book Chance & Necessity by Jacques Monod. The book was written 36 years ago but that doesn't seem to faze the IDiots. Anything that conflicts with their worldview is a target. See [Classic Darwinian Texts — (soon to be, if not already) On the Ash Heap of History].

Here's what GilDodgen has to say,

Read Monod’s book — a foundational Darwinian text. Nowhere in it does he ever address probabilistic resources; he just assumes on faith that random mutation and natural selection can produce everything.

Now I've seen some pretty stupid things over at the Dembski headquarters but calling Monod's book "a foundational Darwinian text" just about takes the cake. This is not classic Darwinism. Classic Darwinism tries to deny the role of chance as much as possible. What Monod does is emphasize the importance of chance and contingency.

The entire book is devoted to addressing the probability of evolution—something that seems to have escaped the notice of IDiots like GilDodgen. Here's a short excerpt from pages 43-44 where Monod explains his view of probability and the inability of natural selection to make predictions.

The thesis I shall present in this book is that the biosphere does not contain a predictable class of objects or of events but constitutes a particular occurrence, compatible indeed with first principles, but not deducible from those principles and therefore essentially unpredictable.

Let there be no misunderstanding here. In saying that as a class living beings are not predictable on the basis of first principles, I by no means intend to suggest that they are not explicable through these principles—that they transcend them in some way, and that other principles, applicable to living systems alone, must be invoked. .... All religions, nearly all philosophies, and even a part of science testify to the unwearying, heroic effort of mankind desperately denying its own contingency.

That ain't Darwinian, baby. Can you imagine Richard Dawkins ever saying that we are here by chance? And it sure as heck ain't intelligent design either—that's the part that annoys the IDiots.
The classic quote from Monod's book can be found on page 112. He discusses the various kinds of mutations that had been discovered by 1971. Then he concludes,

We call these events accidental; we say that they are random occurrences. And since they constitute the only possible source of modifications in the genetic text, itself the sole repository of the organism's hereditary structure, it necessarily follows that chance alone is at the source of every innovation, of all creation in the biosphere. Pure chance, absolutely free but blind, at the very root of the stupendous edifice of evolution: this central concept of modern biology is no longer one among other possible or even conceivable hypotheses. It is today the sole conceivable hypothesis, the only one that squares with observed and tested fact. And nothing warrants the supposition—or the hope—that on this score our position is ever likely to be revised.

You know what surprise me the most about the IDiots? It's not that they are ignorant about evolution, after all there are many scientists who cling to the old-fashioned Darwinian worldview as well. No, the thing that surprises me is that the IDiots are completely incapable of recognizing the different points of view within evolutionary biology. Here we have an example of an IDiot who has read Chance & Necessity but still calls it "a foundational Darwinian text." The mind boggles at such stupidity.

Memo to IDiots: there's more to evolution than Darwinism.

Of course GilDodgen can't resist taking a few other potshots at Monod. After all, Monod is French, an atheist, and (gasp!) a socialist to boot. Those evil socialist evolutionists, where do they get off caring for the downtrodden and the oppressed?

Footnote: GilDodgen begins his rant with,

I just pulled out my 1972 edition of Jacques Monod’s “classic” work, Chance and Necessity, subtitled A Philosophy for a Universe without Causality.

He can't even get the subtitle right. What he's quoting is a blurb on the cover that says "A philosophy for a universe without causality—by the Nobel Prize-winning French biologist." The actual subtitle is "An Essay on the Natural Philosophy of Modern Biology."

What Is a Valid Argument?

 
As part of the basic concept series, Janet Stemwedel explains arguments [Basic concepts: arguments]. For example, she says,

Here's an example of a valid argument:
1. Britney Spears is from Mars. (premise)
2. Martians have astounding vocal range and are great dancers. (premise)
3. Hence, Britney Spears has astounding vocal range and is a great dancer. (conclusion)

Are you convinced that this is a valid argument?

DNA Packaging and DNA Replication

 
The first part of this video shows how long strands of DNA are packaged in eukaryotic cells. It's pretty good. The second part is a demonstrating of how the replisome works. The replisome is a little molecular machine that copies DNA. The animation doesn't do a very good job of conveying the idea that the various components of the replisome interact with each other to form a compact blob at the replication fork.

The concept of a "molecular machine" was promoted by Bruce Alberts who worked on DNA replication. It gets the IDiots all in a tizzy whenever we talk about molecular machines. They think we're advocating intelligent design!



[Hat Tip: Living the Scientific Life]

A Typical Graduate Course in Biochemistry

 
Vince LiCata was kind enough to publish a generic course syllabus that applies to most graduate courses—and many senior undergraduate courses. Read it at MY NEW GRADUATE COURSE OFFERING.

[Hat Tip: The World's Fair]

Student Evaluations Don't Mean Much

Inside Higher Ed has just commented on a new study of student evaluations [New Questions on Student Evaluations]. The results are not surprising. They confirm all previous studies showing that student evaluations aren't what everyone thinks they are.

Previous studies suggested that students are rating generosity and personality and not quality of teaching. For example, a study of ratings on RateMyProfessor [‘Hotness’ and Quality] showed that,

... the hotter and easier professors are, the more likely they’ll get rated as a good teacher. As far as students — or whoever is rating professors on the open Rate My Professor site — are concerned, nothing predicts a quality instructor like hotness.

The new study from Ohio State University finds "... a strong correlation between grades in a course and reviews of professors, such that it is clear that students are rewarding those who reward them." Duh!

Now a cynic might say that this simply means that good teachers are doing such a good job that their students get higher grades. Thus, the evaluations truly represent the quality of the teacher and not how easy they mark. Well, that's not what the study suggests,

The Ohio State study, however, provides evidence for the more cynical/realistic interpretation — namely that professors who are easy (and aren’t necessarily the best teachers) earn good ratings. The way the Ohio State team did this was to look at grades in subsequent classes that would have relied on the learning in the class in which the students’ evaluations were studied. Their finding: no correlation between professor evaluations and the learning that is actually taking place.

The authors of the report show that student evaluations are practically worthless but in the interest of appeasing students they close with a mealy-mouthed sop as reported on the Inside Higher Ed site,

The authors stress that there are many ways — such as adjusting for student bias for easy graders or bias against certain groups of instructors — to continue to use student evaluations as one tool for measuring professors’ performance. But they write that, used alone and unadjusted, they appear highly questionable.

Let's see if I understand this logic .... student evaluations are biased and useless but instead of abolishing them we continue to use them to measure Professor's performance as long as we use other criteria as well.

Why? Why not get rid of student evaluations? We've known for decades that they don't work. Let's try and find another way for students and Professors to work together to improve university education. Student evaluations are ignored by all responsible Professors and they give students the false impression that their opinion is valued.

There has to be a better way. I believe that university students can provide useful and constructive criticism but only if they give up on the popularity contest and stop pretending that it has anything to do with quality of learning.

(As I write this, I'm supposed to be making up exam questions. I think I'll make some of them a bit easier .... )

[Hat Tip: Uncertain Principles]

Engineers Learn Workplace Skills

 
From the University of Toronto website comes this press release about how engineers learn workplace skills that will help them in their careers. The first two paragraphs are,

Gathered in the main dining room of the Faculty Club on the evening of Jan. 17, more than 100 engineering students sat down for an important professional lesson: dining etiquette. Led by Faculty Club manager Leanne Pepper, students were taken through the dos and don’ts of a five-course meal.

Organized by the Leaders of Tomorrow (LoT) program in chemical engineering and applied chemistry, the dining etiquette session was one of a series of talks and workshops that aim to develop the broader skills needed for engineers in the workplace.

Leanne is a friend of mine so I'll resist commenting.

Guernica

 
Remember Guernica? Thanks to the team of senior public health scientists and practitioners at Effect Measure for finding this video.

Is Nutritional Science Really a Science?

 
I have my doubts, and so does Jonah Lehrer [Why is Nutritional Science So Bad?].

John Kasich Interviews Atheist Brian Flemming about the Blasphemy Challenge

 
We don't get FOX News up here so I've never seen this John Kasich dude in action. Watch him interview Brian Flemming, the originator of the Blasphemy Challenge, at [onegood move]. With people like John Kasich around we have a long way to go before the majority gives up their supersitutions and becomes rational.

Kasich just doesn't get it. One is left with the distinct impression that Kasich has never, ever, questioned his religious beliefs. In other words, he has been so thoroughly brainwashed that alternative viewpoints just don't exist for him. Disgusting.

[Hat Tip: RichardDawkins.NET]

Monday's Molecular #11

 
Name this molecule. You must be specific. We need the correct common name.

This is another easy one for everyone who has ever taken biochemistry. This compound is one of the most important energy molecules in living cells. We will discuss the very important reactions that result in synthesis of this molecule after you've been given a chance to identify it.

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

What Is a Gene?

(Other definitions are at Discovering Biology in a Digital World, Pharyngula, and Greg Laden.)

The concept of a gene is a fundamental part of the fields of genetics, molecular biology, evolution and all the rest of biology. Gene concepts can be divided into two main categories: abstract and physical. Abstract genes are the kind we refer to when we talk about genes “for” a certain trait, including many genetic diseases. Most geneticists and many evolutionary biologists use an abstract gene concept.

Philosophers have coined the term “Gene-P” for the abstract gene concept. The “P” stands for “phenotype” indicating that this gene concept defines a gene by it’s phenotypic effects and not its physical structure.

Physical genes consist of stretches of DNA with a beginning and an end. These are molecular genes that can be cloned and sequenced. Philosophers call them “Gene-D” where “D” stands for “development”—a very unfortunate choice.

This essay describes various modern definitions of physical genes (Gene-D). I like to define a gene as “a DNA sequence that’s transcribed” but that’s a bit too brief for a formal definition. We need to include something that restricts the definition of gene to those entities that are biologically significant. Hence,

A gene is a DNA sequence that is transcribed to produce a functional product.

This eliminates those parts of the chromosome that are transcribed by accident or error. These regions are significant in large genomes; in fact, the confusion between accidental transcripts and real transcripts is responsible for the overestimates of gene number in many genome projects. (In technical parlance, most ESTs are artifacts and the sequences they come from are not genes.)

We could refine the definition by including RNA genes but that’s such a insignificant percentage of all genes that the refinement is hardly worth it. As we shall see, there are more significant limitations to the definition.

This "DNA sequence that's transcribed" definition describes a physical entity. Let’s examine a simple molecular gene to see how the definition applies.

This is a simple bacterial protein-encoding gene. The horizontal line represents a stretch of double-stranded DNA with the rectangular part being the gene. The gene is copied into RNA as shown by the arrow below the gene. This process is called transcription. Transcription begins when the transcription enzyme (RNA polymerase) binds to a promoter region (P) and starts copying the DNA beginning at the initiation site (i). The DNA is copied until a termination site (t) is reached at the end of the gene. According to my preferred definition of a gene, it starts at “i” and ends at “t.”

The part of the gene that’s transcribed includes the coding region, shown in black. This is the part of the gene that contains sequential codons specifying the amino acid sequence of the protein. At the beginning of the gene, called the 5ʹ (5-prime) end, there’s a short stretch of sequence that will be transcribed but not translated into protein. This 5ʹ untranslated region (5ʹ UTR) will contain various signals for starting protein synthesis.

The other end of the gene is called the 3ʹ (3-prime) end and there’s almost always a stretch that’s transcribed but not translated (3ʹ UTR). The 3ʹ UTR contains signals that cause transcription termination and also signals that regulate translation.

There are regions upstream of the promoter that control whether or not the gene is transcribed. These regions are called regulatory regions. They may contain binding sites for various proteins that will attach there in order to enhance the binding of RNA polymerase to the promoter. One of the differences between my preferred definition of a gene and others is that some other definitions include the promoter and the regulatory region.

There are two problems with such definitions. First, they’re not consistent with standard usage when we talk about the regulation of gene expression. We don’t say that only “part” of a gene is transcribed, which would be correct if we included the regulatory region in our definition of a gene. How often have we heard anyone say that regulatory sequences control the expression of part of the gene? That doesn’t make sense.

Second, by including regulatory sequences in the definition of a gene the actual extent of the gene becomes ill-defined. For most genes, we don’t know where all the regulatory sequences are located so we don’t know for sure where the gene begins or ends. Furthermore, there are some regulatory sequences, especially in eukaryotes, that are not contiguous with the gene and this leads to “genes” that are split into various pieces. It’s much easier to use a definition like “a DNA sequence that’s transcribed” because it defines a start and an end.

The organization of a typical eukaryote gene is shown below.

The main difference between this type of gene and a typical bacterial gene is the presence of introns and exons. These genes are transcribed from an initiation site to a termination site just like bacterial genes. When the RNA transcript is finished it undergoes an additional step called RNA processing. In that step, parts of the original transcript are spliced out and discarded. These parts correspond to the introns in the gene—shown as thinner rectangular region within the genes.

Note that the coding region (black) can be interrupted by these introns so the final messenger RNA (mRNA) cannot be translated until RNA processing is completed. The important point for our purposes is that the introns are part of the gene since they are transcribed.

My preferred definition has been used by molecular biologists for many decades but there are several other definitions that have been popular over the years. All of them have good points and bad points. I’ve already dealt with the definition that includes regulatory regions.

Some people still prefer a gene definition that corresponds to one used over half a century ago; namely, a gene is a sequence that encodes a polypeptide. This is the so-called one gene:one protein definition. It’s very old-fashioned. We’ve known for years that there are genes that do not encode proteins in spite of the fact that we commonly show protein-encoding genes whenever we describe typical genes. (As I did above.) There are genes for transfer RNA (tRNA), genes for ribosomal RNA, and genes for a large heterogeneous class of small RNAs. None of them have coding regions. The transcript is the functional product, often after RNA processing.

Because this old-fashioned definition is rarely used, the examples of alternative splicing producing different proteins pose no problem for modern definitions. These modern definitions refer to the transcript as the important product and not a protein.

There are exceptions to every generality in biology. Here’s a short list of gene examples that do not conform to my preferred definition.

Operons: In some cases adjacent “genes” are transcribed together to produce a large initial transcript containing several coding regions. In other cases the primary transcript is subsequently cleaved to produce multiple functional RNAs. In these cases it doesn’t make sense to refer to the co-transcribed genes as a single “gene.” Instead, we identify the stretches of DNA that correspond to a single functional unit as the “gene.” Thus, the lac operon contains three “genes” and the ribosomal RNA operons contain two, three, or four genes.

Trans-splicing: There are examples of “genes” that are split into pieces. The transcript from one piece is joined to the transcript from another to produce a functional RNA.

Overlapping Genes: Some “genes” overlap. This means that a single stretch of DNA can be part of two, and in at least one case, three genes.

RNA Editing: In some cases the primary transcript is extensively edited before it becomes functional. In the most extreme cases nucleotides are inserted and deleted. What this means is that the information content of the “gene” is insufficient to ensure a functional product and the assistance of other “genes” is required.

The Richard Dawkins Definition of a Gene Is Seriously Flawed

(This is an updated version of an article that I originally posted to talk.origins on Sept. 6, 1999)

We are interested in the correct definition of a "gene" (see ...). Part of the confusion is due to popular science writers who don't get it right. For example, Richard Dawkins does some serious handwaving in The Selfish Gene and he compounds it in The Extended Phenotype.

Dawkins knows that his defintion of "gene" in the Selfish Gene is unusual so he returns to the subject in The Extended Phenotype in his discussion of the selfish replicator. Dawkins is forced to concede that his use of the word "gene" is incorrect. That's why he says,

I am happy to replace 'gene' with 'genetic replicator where there is any doubt.

Nevertheless, he tries very hard to defend his point of view by claiming that geneticists and molecular biologists can't come up with a good definition of gene either. This leads him to make some very silly statements about genes and cistrons. He defines his genetic replicators in terms of alleles which means that they don't exist unless there is variation in the genome. He then goes on to restrict his discussion of changes in frequency to the results of natural selection, which means that his "genes" are effectively defined by the mechanism he prefers. This is why he quotes George Williams,

This is the rationale behind Williams's definition: 'In evolutionary theory, a gene could be defined as any hereditary information for which there is a favorable or unfavorable selection bias equal to several or many times its rate of endogenous change.'
                ....The Extended Phenotype p.89

The hand-waving in The Selfish Gene is even more obvious,

In the title of this book the word gene means not a single cistron but something more subtle. My definition will not be to everyone's taste, but there is no universally agreed definition of a gene. Even if there were, there is nothing sacred about definitions. We can define a word how we like for our own purposes, provided we do so clearly and unambiguously. The definition I want to use comes from G.C. Williams. A gene is defined as any portion of chromosomal material that potentially lasts for enough generations to serve as a unit of natural selection.
                ....The Selfish Gene p.28

In the new version of The Selfish Gene (1989) Dawkins adds a footnote where he again addresses his critics, especially Sewall Wright. Dawkins defends his definition of a gene as a unit of selection.

More handwaving,

I am using the word gene to mean a genetic unit that is small enough to last for a number of generations and to be distributed around in many copies. ... The more likely a length of chromosome is to be split by crossing-over, or altered by mutations of various kinds, the less it qualifies to be called a gene in the sense I am using the term.
                ....The Selfish Gene (1989) p.32

I said that I preferred to think of the gene as the fundamental unit of natural selection, and therefore the fundamental unit of self-interest. What I have now done is to *define* [Dawkins' emphasis] the gene in such a way that I cannot really help being right!
                ....The Selfish Gene (1989) p.32

The fact that Dawkins uses the word "gene" in such a non-standard way is not an issue as long as one recognizes that the Dawkins "gene" has nothing to do with the genes that molecular biologists and geneticists talk about. It's not an issue as long as one doesn't try and pretend that Dawkins has avoided handwaving and "clearly" refuted the problems raised by his critics.

The most reasonable definition of gene is that it is a piece of DNA that is transcribed but there are exceptions to everything in biology. Some genes are made of RNA, for example, and sometimes it's better to define a gene in terms of the protein it encodes. In no case is it reasonable to define a gene in terms of its ability to be selected or whether recombination can occur within it.

Jane Fonda Is Back

 
It's about time. Jane Fonda spoke at the Washington rally for peace yesterday. She said "I haven't spoken at an anti-war rally for 34 years. But silence is no longer an option." Jane is right. Silence is no longer an option. We need to get out of Iraq and Afghanistan.

Many of us will remember when "Hanoi Jane" visited North Vietnam in 1972. Is it time for her to visit Iraq?

[Photo Credit: According to Wikipedia "This photograph was shot by a public affairs officer of the Peoples Republic of Vietnam, and released worldwide for distribution."]

Psychic Sylvia Browne Is Nothing but a Con Artist and a Fake

 
Anderson Cooper on CNN does something right. He exposes Sylvia Browne as a con artist. She told the parents of a missing boy that their son was dead but he turned up alive after four years. James Randi takes part in the debunking.

Now, if only we could get Larry King to admit that psychics are frauds ....