Theme: Transcription

 
Transcription is one of the key steps in the flow of information from gene to protein. Transcription is the process by which information in double-stranded DNA is copying into a molecule of RNA.

The postings listed below describe the various steps of transcription and the structure of RNA polymerase.

March 19, 2007
Monday's Molecule #18. The molecule is α-amanitin, an important inhibitor of RNA polymerase.

March 19, 2007
Gene and Transcription Orientation. This article describes the relationship between a gene and its RNA.

March 19, 2007
Transcription. Covers the essentials of transcription: initiation, elongation, termination.










March 20, 2007
Mushrooms for Dinner. How Julia Agrippina disposed of her husband and put her son, Nero, on the throne.

March 20, 2007
Eukaryotic RNA Polymerases. Describes the five different kinds of RNA polymerase in eukaryotic cells.






March 21, 2007
Nobel Laureate: Roger D. Kornberg (Chemistry 2006) "for his studies of the molecular basis of eukaryotic transcription"

March 21, 2007
How RNA Polymerase Works: The Chemical Reaction. This posting explains the chemical reaction of RNA polymerization.

March 22, 2007
How RNA Polymerase Works: The Topology of the Reaction and the Structure of the Enzyme. The structure of RNA polymerases is illustrated using the yeast and E. coli enzymes as examples. How RNA polymerase succeeds in unwinding RNA from it's DNA template is described.

March 25, 2007
RNA Polymerase Genes in the Human Genome. This article was written for Gene Genie. It describes the locations of the human genes for RNA polymerase subunits.



August 7, 2007
Hype and Reality in an Important Transcription Paper. A discussion of a recent paper demonstrating the actions of RNA polymerases in mammalian nuclei.

September 27, 2007
Transcription of the 7SL Gene. How the 7SL gene is transcribed by RNA polymerase III and the significance of internal promoters in creating junk DNA.

February 7, 2008
Junk RNA. Much of the mammalian genome may be transcribed by accident and the resulting RNAs are quicky degraded.

February 7, 2008
Regulation of Transcription. An overview of the main forms of transcriptional regulation.

February 12, 2008
Repression of the lac Operon. This is a description of the binding properties of lac repressor, used as an introduction to DNA binding proteins.

February 12, 2008
Transcription Factors Bind Thousands of Active and Inactive Regions in the Drosophila Blastoderm. Transcription factors bind to thousands of sites on the Drosophila genome. Many of the sites appear to be non-functional.

What Is the Cause of Genetic Differences in Domesticated Rice Varieties?

 
There are two main varieties of domesticated rice (Oryza sativa). One variety, O. sativa indica can be found in India and Southeast Asia while the other, O. sativa japonica, is mostly cultivated in Southern China.

Extensive studies of the varieties has demonstrated that they were independently derived from the wild rice species Oryza rufipogon (left). The domesticated varieties show much less variation (polymorphism) than the wild species. This is not unexpected since they were presumably bred from a small number of plants when rice first began to be cultivated more than 10,000 year ago. This phenomenon of restricted variation after a speciation event is called the bottleneck effect because it represents a severe reduction in the number of different individuals that contributed to the new species. This bottleneck effect is thought to be a major factor in reducing variation in domesticated strains as well. In this case, the "speciation" event is man-made.

Bottleneck effects are similar to founder effects and both of them are forms of random genetic drift. The changes in the frequency of alleles within the new populations are due to chance and not to adaptation.

Caicedo et al. (2007) have recently explored the patterns of nucleotide polymorphisms in rice. They looked at SNP's, or single nucleotide polymorphisms, in 111 different regions of the genome. The idea was to see if certain polymorphisms tended to cluster together to form distinct patterns. If one genetic locus had a particular nucleotide "A" at site SNP-32, for example, it would be interesting to see whether the nearby regions of the genome were similar or different. If the same pattern, say SNP-32(A), SNP-33(G), and SNP-34(T), occurred at a high frequency then it indicates that there hasn't been enough time for recombination to separate the three distinctive variations.

When such patterns are found, there's a tendency to attribute the pattern to "selective sweeps." In a selective sweep the pattern becomes rapidly fixed in the genome due to selection for one of the markers. Assume, for example, that the presence of nucleotide "G" at site SNP-33 conferred some selective advantage on the plant. As this allele is rapidly selected, the nearby alleles (SNP-32(A) and SNP-34(T)) will be swept up in the adaptive event. Their frequency in the population will increase because they are hitchhiking on the SNP-33(G) allele. It's important to remember that the fixation of the flanking alleles are accidents—they are not being selected for their own phenotype.

But selective sweeps are not the only way that specific patterns of alleles can become widespread in a population. It can also happen if the population goes though a bottleneck where much of the variation was eliminated by chance. If the bottleneck occurred relatively recently then the pattern can look very much like a rapid fixation due to adaptation and hitchhiking.

The pattern of evolution in domestic rice varieties compared to Oryza rufipogon shows many examples of associated alleles, or haplotypes. The O. japonica variety has only 19% of the total polymorphism of the wild type genome and the other main variety, O. indica, has only 43%. The authors note that such patterns are often associated with selected sweeps but there are other possibilities.

An excess of high-frequency derived SNPs is often interpreted as a result of genetic hitchhiking during recent selective sweeps [26]. Because the site-frequency spectrum in rice varieties is observed from randomly selected loci, and the loci contributing high frequency derived SNPs are distributed across the genome (Fig. S4), this pattern suggests that strong linkage to positively selected mutations occurred within most of the genome. However, demographic forces may have also played a role in shaping the rice genomes. We developed several demographic models and a multiple selective sweeps model to test which evolutionary processes may best explain the observed patterns of polymorphism in rice.

In addition to a selective sweep model, the authors tested a neutral population bottleneck model defined as,

The most widely accepted demographic model for crop domestication is a neutral bottleneck model [27-29]. In this model, rice domestication is assumed to be a result of recent population divergence, with one of the two daughter populations experiencing a reduction in population size at divergence associated with the founder effect at the time of domestication, followed by population growth as cultivation of the crop increases.

The other models were combinations of bottleneck and migration between populations, and bottleneck plus selection.

It isn't easy to test these models, even with an extensive database such as the one from rice genomes. The mathematics is complicated and many simplifying assumptions have to be made. Nevertheless, Caicedo et al. (2007) conclude from their analysis that bottlenecks alone are not sufficient to explain the SNP patterns they see in domesticated rice. They conclude that the patterns result from a combination of drift (bottlenecks) and adaptation (selective sweeps).

A more complex demographic scenario involving very strong bottlenecks that led to the fixation of alternate alleles during the two rice domestication events (with concurrent gene flow between variety groups) can explain the site-frequency spectrum of indica and O. rufipogon. However, this pure demography model requires a bottleneck four-fold stronger in indica and twice as strong in tropical japonica relative to the model that incorporates selection (Table 2; Figure 5), and a relatively high migration rate between domesticated rice and wild O. rufipogon populations. It is also important to note that the model is a poor fit to the observed frequency distribution of alleles in tropical japonica.

Domestication, however, is characterized by strong directional selection on a suite of traits that lead to the establishment of cultivated species as distinct entities from their wild progenitors within agricultural settings. We show that, in contrast to the complex demographic model, a simple bottleneck with sweeps model fits data from both tropical japonica and indica well without requiring an extremely strong domestication bottleneck. Since domesticated Asian rice has been subject to artificial selection, the selection plus demography model is a very plausible explanation for the observed strong excess of high frequency derived alleles in domesticated rice varieties, and is consistent with recent reports about domestication genes in rice [45,46].

The lesson here is that it is very difficult to distinguish selection from drift and one should be cautious in attributing results to only one of these mechanisms of evolution.

---

Caicedo, A., Williamson, S., Hernandez, R.D., Boyko, A., Fledel-Alon, A., et al. (2007) Genome-Wide Patterns of Nucleotide Polymorphism in Domesticated Rice. PLoS Genet. In press. [doi:10.1371/journal.pgen.0030163.eor]

[The drawing of Oryza rufipogon is from Naples, M.L. (2005). The middle photograph is of Japanese short grained rice from the Wikipedia article on rice. The lower figure is Figure 3 from Caicedo et al. (2007)]

Monday's Molecule #38

 
Today's molecule is actually several molecules. In order to win the reward you have to identify what's going on and make the connection to Wednesday's Nobel Laureate(s).

The reward (free lunch) goes to the first person who correctly identifies the molecules and the Nobel Laureate(s) when comments are unblocked.^*

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

^*Previous free lunch winners are ineligible for one month from the time they first collected the prize. There's only one (Marc) ineligible candidates for this Wednesday's reward since many recent winners haven't collected their prize. The prize is a free lunch at the Faculty Club.

What Is Creationism?

Denyse O'Leary recently posted some comments on the Creation Museum funded by Answers in Genesis [ Creationism and popular culture: A friend visits Kentucky's Creation Museum]. It's a typical comment from an Intelligent Design Creationist. She does not speak out against the false science in the museum; instead, she tries to draw a distinction between her own personal beliefs and those of the Young Earth Creationists. According to Denyse O'Leary, Intelligent Design Creationism is not Creationism. (Why is it that the moderate Intelligent Design Creationists can be so hard on scientists while turning a blind eye to the blatant stupidity of the Young Earth Creationists?)

Mike Dunford agrees with Denyse O'leary in The Big Difference Between Creationism and Intelligent Design. He says,

It's extremely uncommon for me to find myself in agreement with Denyse on anything (and it's not a comfortable feeling), but in this case I do think she's got a good point. Creationism is certainly explicitly based on the Bible, and Intelligent Design certainly is not.

There are several different ways of defining "creationism." I prefer the definition that refers to "creationists" as people who believe that the universe was created by God. In some cases God just set up the original universe with all its laws of physics and chemistry, while in other versions of creationism he/she did some meddling after the initial creation event.

Young Earth Creationists are those who take the Bible literally. Old Earth Creationists are creationists who accept some parts of science and reject a literal interpretation of Genesis. Intelligent Design Creationists are creationists who believe that there is scientific evidence to support the creation event(s). Some Intelligent Design Creationists are also Young Earth Creationists while others are Old Earth Creationist and still others are closer to Theistic Evolutionists.

The supporters of Theistic Evolution are also creationists because they believe in a creator who created some part of the existing universe while, at the same time, accepting most of evolution. Deism is the softest version of creationism and the one most compatible with science.

I think the Wikipedia article on Creationism has it right when it says,

Creationism is the belief that humanity, life, the Earth, and the universe were created in their entirety by a deity or deities (typically God), whose existence is presupposed.[1] In relation to the creation-evolution controversy the term creationism (or strict creationism) is commonly used to refer to rejection of evolution. The wide spectrum of such beliefs includes young Earth creationism holding a very literal interpretation of Genesis, while old Earth creationism accepts geological findings but rejects evolution. The term theistic evolution has been coined to refer to beliefs in creation which are compatible with scientific findings on evolution and the age of the Earth.

On this day in 1945 ....

 
At 8:15 AM on August 6, 1945 an atomic bomb was detonated over Hiroshima, Japan. Approximately 78,000 civilians were killed on that day. Six months later the death toll had risen to about 140,000 people.

There are many arguments in favor of dropping the bomb just as there are many arguments against it. What's clear is that in the context of 2007 we are not in a good position to judge the actions of countries that had been at war for many years.

The most important lesson of Hiroshima is that war is hell and many innocent people die. It's all very well to enter into a war with the best of intentions—as the Japanese did on December 7, 1941—but it's foolish to pretend that when you start a war there won't be any suffering. When you do that you can really say that the victims of Hiroshima died in vain.

The killing and maiming of civilians is an inevitable outcome of war, no matter how hard you might try to restrict your targets to military objectives. Before going to war you need to take the consequences into account and decide whether the cost is worth it.

One of the many mistakes in Iraq was the naive assumption that it would be a clean war with few casualties and no long-term consequences for the Iraqi people. Yet today, the numbers of innocent lives lost in Iraq is comparable to the numbers lost in Hiroshima and Nagasaki. And what is the benefit for Iraq that outweighs the cost in human lives? Is it "freedom" and "democracy"?

Hiroshima was not a glorious victory. It was ugly, heartbreaking, and avoidable. War is not an end in itself, it is the failure of peace. War is not an instrument of your foreign policy—it is an admission that you don't have a foreign policy.

[The top photograph shows the mushroom cloud over Hiroshima on the morning of August 6, 1945 (Photo from Encyclopedia Britanica: Hiroshima: mushroom cloud over Hiroshima, 1945. [Photograph]. Retrieved August 7, 2007, from Encyclopædia Britannica Online. The bottom image is taken from a Japanese postcard (Horoshima and Nagassaki 1945). It shows victims of the attack on Hiroshima.]

A Citation Classic: Nirenberg & Matthaei

 
John Dennehy has described a classic paper on cracking the genetic code. Read about the Nirenberg & Matthaei experiment and how it was received at [This Week's Citation Classic] on The Evilutionary Biologist.

John also likes my description of the experiment but he thinks I should delete my posting now that he has put up a better one. Ain't gonna happen.

DNA Replication Video

 
Hsien-Hsien Lei found this video of DNA replication [DNA Video: Molecular Visualization of DNA Replication]. It looks pretty accurate to me. The replication complex of proteins forms a molecular machine at the replication fork and it copies both strands of the parent DNA. The lagging strand has to be replicated in the opposite direction and that's what give rise to the large loops that are formed and then released.

Visit Sandwalk in California

 

Next time you're in Sandwalk why not look up some movie stars?

Fix Hollywood yourself at [Hollywood Sign].


[Hat Tip: Canadian Cynic]

Mendel's Garden #17

 


The 17th version of Mendel's Garden has just been posted on ScienceRoll [Mendel’s Garden #17: Blog Carnival of Genetics].

Crime Increases When the Moon Is Full

 
Friday's Urban Legend: False

CURRENT MOON

lunar phase

Last weekend I was in Ottawa and I read an article in The Ottawa Citizen claiming there was a link between a full moon and crime rates. This silly myth has been around for decades and it's disappointing that newspaper reporters are still promoting it. It's relatively easy to find sites that debunk all of the studies claiming to find a correlation between the phases of the moon and crime, sex, traffic accidents, and emergency room admissions.

Check out The Bad Astronomer for his latest rant [Full Moon Effect Debunked Again] or go directly to The Skeptics Dictionary for all the gory details [full moon and lunar effects].

Propaganda Techniques: Shift the Burden of Proof

 
I've been covering some of the common techniques of debate and propaganda. You can see the complete list at [Propaganda and Debating Techniques].

The technique of shifting the burden of proof onto your opponent is often encountered when we deal with religious leaders who are responding to criticisms of the common arguments for the existence of God. Here's the description of this tactic.

Shift the Burden of Proof Onto Your Opponent

Make all kinds of unsubstantiated statements and claims, and when your opponent objects and challenges those statements, say, "Do some research on the subject and you will see that what I am saying is true."

It is the job of the person who is making the statements and claims to do the research and supply the evidence to support his assertions.

Here's a classic example of this tactic in an interview of Alister McGrath on the National Catholic Register website [All’s Not Quiet on The Atheistic Front]. McGrath says,

A second point, which clearly follows on from this, is that Dawkins clearly believes that those who believe in God must prove their case and atheists have nothing to prove because that’s their default position. But I think that’s simply incorrect and it’s obviously incorrect.

Really, the only obvious position is to say: We don’t know, we need to be persuaded one way or the other. The default position in other words is: not being sure.

Therefore I think Dawkins must realize that he’s under as great an obligation to show that there is no God as, for example, a Christian is to show that there’s a God. Those are two very fundamental problems I have with his approach before we go any further.

This is a totally fallacious argument and it's surprising to see it coming from an Oxford Professor. However, I had a chance to hear McGrath speak in May and I can assure you that he really is this ignorant [Alister McGrath].

It is not up to Richard Dawkins to prove that God doesn't exist. He's not the one making the claim. It's the believers who are making the extraordinary claim that supernatural beings exist and that they control our lives. And that we should worship them. The world is really turning upside down when the believers demand that we atheists have to prove the non-existence of everything that was ever postulated.

Of course that's not the way they see it. They think it would be nonsense for them to have to prove that the Flying Spaghetti Monster (or Santa Claus) doesn't exist. What that kind of reasoning demonstrates to me is that there's a powerful correlation between superstition and irrationality.

Imagine that someone went up to McGrath and told him that aliens are using a mind altering probe to take over the British government. How do you think he would respond? According to his version of logic he would have to say. "Hmmm, that's very interesting. You may be right but I'm just not sure. Let me get to work on trying to prove that aliens don't exist."

McGrath commits another common fallacy but I'm not sure this one has a name. Here it is ...

... as someone who has studied the history of science, I am very much aware that what scientists believe to be true in the past has been shown to be wrong or has been overtaken by subsequent theoretical developments.

One of my concerns is that Dawkins seems very, very reluctant to concede radical theory-change in science. In other words, this is what scientists believe today but we realize that tomorrow they might think something quite different. He seems to think that science has got everything forced out and that’s it, whereas my point is that as we progress we often find ourselves abandoning earlier positions.

So my question, therefore, is: How on earth can Dawkins base his atheism on science when science itself so to speak is in motion, in transit?

According to this line of argument, no scientific concepts could ever be used to support any kind of argument because all science is transient. Yes, this is a form of Reductio Ad Absurdum but not all of these are wrong. If McGrath wants to argue that only some scientific concepts fall into the category of "transient" then he should have made it clear that he was dealing with a subset of what science believes. I'm willing to bet that he isn't as skeptical about everything scientific. Maybe it's McGrath who is committing the error of reductio ad absurdum?

McGrath also says something I agree with.

What I do think is enormously important is to mount a public defense of the Christian faith that shows it as reasonable, attractive and plausible. That really is something that needs to be done, and that’s why I wish we had more people like G.K. Chesterton, C.S. Lewis or J.R.R. Tolkien, who spoke so powerfully in the past. I think there’s a real need for the Church to regain its apologetic dimension and to be really able to speak with confidence and conviction about faith in the public domain.

So far I've read books by Bill Dembski, Phillip Johnson, Jonathan Wells, Michael Behe, Michael Denton, Francis Collins, Ken Miller, and Simon Conway-Morris. I've also read four or five articles by Allister McGrath. All of them are Christians and all of them have tried to show me that their religion is "reasonable, attractive, and plausible." If that's the best they can do then Christianity is in big trouble.

Propaganda Techniques: Observational Selection

 
There's a list of common propaganda techniques at [Propaganda and Debating Techniques]. It's well worth reading in order to familiarize yourself with common fallacies that we all commit from time-to-time.

There's one trick we know all too well. You've probably been guilty—I know I have. It's called Observational Selection.

Observational Selection

Observational selection, also known as "cherry-picking", is a tactic like counting the hits and forgetting the misses. See only what you wish to see. Overlook and ignore evidence you don't wish to see. And encourage your audience to be equally blind. Observational selection will destroy the validity of any statistical study.

Here's an example of this technique from the CNNMoney.com website [A Turn For The Better In Iraq?]. In this case, the author picked out a single article from The New York Times written by Brookings Institution scholars Michael O'Hanlon and Kenneth Pollack [A War We Just Might Win]. Those scholars pointed out that some progress was being made in Iraq in stabilizing the country. The significance of the New York TImes piece is that O'Hanlon and Pollack have been, and continue to be, critical of the Bush policies in Iraq. The other significance is that some editor selected a misleading title for their article, "A War We Just Might Win." The authors have appeared on television to criticize that choice of title as misleading.

Here's part of what O'Hanlon and Pollack say,

Here is the most important thing Americans need to understand: We are finally getting somewhere in Iraq, at least in military terms. As two analysts who have harshly criticized the Bush administration’s miserable handling of Iraq, we were surprised by the gains we saw and the potential to produce not necessarily “victory” but a sustainable stability that both we and the Iraqis could live with.

The author of the CNNMoney.com article cherry-picked from this opinion piece and published the following under the title "A Turn For The Better In Iraq?"

War In Iraq: It's quite likely that, as you read this, U.S. troops under the leadership of Gen. David Petraeus are winning the war against terrorism in Iraq. And no, it isn't just war-crazed neocons who think so.

The possibility that the U.S. is winning this war -- and not losing, as Democrats would have it -- was raised in the pages of no less than the New York Times just this week.

In a long, thoughtful op-ed following an eight-day trip to Iraq, Brookings Institution scholars Michael O'Hanlon and Kenneth Pollack wrote about the progress there -- and what's at stake.

Remember: Brookings generally is a liberal -- not conservative -- think tank, though neither O'Hanlon nor Pollack is in any sense a doctrinaire leftist. That said, the two have been to Iraq before and are no great fans of President Bush. But the changes they saw this time were, in their words, "significant."

Notice that this particular article by Brookings Institute scholars is "thoughtful." I wonder how many other articles from the Brookings Institute are "thoughtful." Perhaps all of them? I doubt it.

Also, note that according to this CNNMoney.com article "U.S. troops ... are winning the war against terrorism." There's nothing in the O'Hanlon and Pollack article that suggest any such thing. What they said was that by backing moderate militia groups, the U.S. army was helping to suppress the most extreme insurgents like those who fight for Al Qaeda. There was no mention of a war against terrorism. I suspect this is because O'Hanlon and Pollack know the difference between a war against terrorism and trying to establish peace and security in Iraq.

They conclude their article with,

In the end, the situation in Iraq remains grave. In particular, we still face huge hurdles on the political front. Iraqi politicians of all stripes continue to dawdle and maneuver for position against one another when major steps towards reconciliation — or at least accommodation — are needed. This cannot continue indefinitely. Otherwise, once we begin to downsize, important communities may not feel committed to the status quo, and Iraqi security forces may splinter along ethnic and religious lines.

How much longer should American troops keep fighting and dying to build a new Iraq while Iraqi leaders fail to do their part? And how much longer can we wear down our forces in this mission? These haunting questions underscore the reality that the surge cannot go on forever. But there is enough good happening on the battlefields of Iraq today that Congress should plan on sustaining the effort at least into 2008.

That doesn't sound like "winning" to me. What happened was that someone who is likely to be a supporter of the war on terrorism picked out a single article by two Bush critics and used it as evidence that "liberals" are now seeing the light and have come 'round to supporting the war on terrorism.

[The photograph is from the US Dept. of Defense and is in the public domain. See Wikipedia: Army.mil-2007-02-13-104034.jpg]

Propaganda Techniques: Appeal to Stupidity

 
There's a list of common propaganda techniques at [Propaganda and Debating Techniques]. It's well worth reading in order to familiarize yourself with common fallacies that we all commit from time-to-time.

Some of the tricks are quite subtle. For example, there's The Appeal to Stupidity.

Appeal To Stupidity

Flaunt an anti-intellectual attitude, and belittle knowledge, wisdom, intelligence and education.

This technique is closely related to "Common Folks" -- "There ain't nobody here but us stupid common folks. I'm just a regular ignorant Joe, just another man of the people."

The IDiots are really, really good at this kind of trick although, in fairness, it may not be a debating trick in their case. Maybe they really are stupid.

Here's an example from a recent posting on Uncommon Descent where someone named Granville Sewell describes his view of Michael Behe's latest book [Trench warfare, not an arms race]. Apparently this person wrote an email message to Behe where he said,

I still insist you don’t need to know any biology at all to have predicted your main conclusions, all you need to know is the second law of thermodynamics: natural forces don’t build bridges, they just destroy them*. But no one will listen to you unless you do know some biology, so I’m glad there are people like you who look at the details and arrive at the same obvious conclusions.

Hmmm, I wonder why nobody will listen to you just because you don't know anything about biology?

Granville Sewell then goes on to make his point even more clearly.

Progress in the battle between Darwinism and ID is judged, by both sides, by who has the most Nobel prize winners and National Academy of Science members (they do!), but for me the whole issue has always been extremely simple. It’s not too complicated for the layman to understand, it’s too simple for the scientist.

Yes siree Bob! Them smart scientists are just too smart for their own good. You have to be a regular ignorant Joe to appreciate why Darwinism is wrong and the IDiots are right. A classic appeal to stupidity.

Boy, you just can't make this stuff up, can you?

Tangled Bank

 



Tangled Bank #85 - The Reductionist's Tale has been posted on Migrations. There's a mechanical duck on the website.

Top 100 Science Sites

 
Here's a list of the top 100 science sites according to TOP100SCIENCE.COM. The links don't work since I just captured the image. You'll have to go to the TOP100SCIENCE website to visit the sites. The NCBI site is only listed at #14—that doesn't seem right.

I don't think there are any blogs in the top 100.



[Hat Tip: Phil Plait whose Bad Astronomy blog comes in at #377]

Nobel Laureates: Max Perutz and John Kendrew

 
 
The Nobel Prize in Chemistry 1962.

"for their studies of the structures of globular proteins"


Max Perutz (1914-2002) and John Kendrew (1917-1997) won the Nobel Prize in 1962 for solving the structures of hemoglobin (Perutz) and myoglobin (Kendrew). This is the same year that Watson, Crick, and Wilkins won for the structure of DNA [Nobel Laureates: Francis Crick, James Watson, and Maurice Wilkins]. Recall that Watson & Crick were working in the Perutz lab at the time of their discovery and Crick was actually working on the structure of hemoglobin as part of his Ph.D. thesis [The Story of DNA (Part 1)].

1962 was also the year that John Steinbeck won the prize for literature [see Nobel Laureates 1962].

The Presentation Speech was given by Professor G. Hägg, member of the Nobel Committee for Chemistry of the Royal Swedish Academy of Sciences. Those of you who weren't yet born in 1955 should make note of the fact that this work required an enormous number of calculations that were only made possible with the help of "a very large electronic computer." Many of my students are surprised to discover that biochemists have been working with computers for over fifty years. Most of them think that computers weren't invented until about 1990 when they were just babies.

Your Majesties, Your Royal Highnesses, Ladies and Gentlemen.

In the year 1869 the Swedish chemist Christian Wilhelm Blomstrand wrote, in his at that time remarkable book Die Chemie der Jetztzeit (Chemistry of Today):

"It is the important task of the chemist to reproduce faithfully in his own way the elaborate constructions which we call chemical compounds, in the erection of which the atoms serve as building stones, and to determine the number and relative positions of the points of attack at which any atom attaches itself to any other; in short, to determine the distribution of the atoms in space."

In other words, Blomstrand gives here as his goal the knowledge of how compounds are built up from atoms, i.e. knowledge of what is nowadays often called their "structure". Moreover, structure determination has been one of the biggest tasks of chemical research, and has been approached using many different techniques. For several reasons, the structure determination of carbon compounds, the so-called organic compounds, experienced an initial rapid development. At this stage the techniques were generally those of pure chemistry. One drew conclusions from the reactions of a compound, one studied its degradation products, and tried to synthesize it by combining simpler compounds. The structure thus arrived at, however, was in general rather schematic in character; it showed which atoms were bonded to a given atom, but gave no precise values for interatomic distances or interbond angles. However, for an up-to-date treatment of the chemical bond and in order to derive a correlation between structure and properties, these values are needed, and they can only be obtained using the techniques of physics.

The physical method which, more than any other, has contributed to our present-day knowledge of these mutual dispositions of the atoms is founded on the phenomenon which occurs when an X-ray beam meets a crystal. This phenomenon, called diffraction, results in the crystal sending out beams of X-rays in certain directions. These beams are described as reflections. The directions and intensities of such reflections depend on the type and distribution of the atoms within the crystal, and can therefore be used for structure determination. It is 50 years ago this year since Max von Laue discovered the diffraction of X-rays by crystals, a discovery for which he was awarded the 1914 Nobel Prize for Physics. This work opened up a whole new range of possibilities for studying both the nature of X-rays and the structure of compounds in the solid state. The initial application of structure determination was developed first and foremost by the two English scientists, Bragg father and son, and as early as 1915 they were rewarded with the Nobel Prize for Physics. The techniques have since been considerably refined, and it has been possible to solve more and more complicated structures. However, considerable difficulties were encountered as soon as any other than very simple structures were considered. There is no simple general way of progressing from experimental data to the structure of the compound under investigation. Moreover, the mathematical calculations are exceedingly time-consuming. However, by about the middle of the 1940's a point had been reached where it was becoming possible to carry out X-ray determinations of the structures of organic compounds which were so complicated that they defied all attempts using classical chemical methods.

In 1937 Max Perutz performed some experiments in Cambridge to find out whether it might be possible to determine the structure of haemoglobin by X-ray diffraction, since no other method could be imagined for this purpose. Sir Lawrence Bragg, who tirelessly continued the work begun jointly with his father, in 1938 became the head of the Cavendish Laboratory in Cambridge. When he saw the results obtained by Perutz, he encouraged him to continue and has ever since lent a very efficient support. Haemoglobin belongs to the proteins which play such an enormous part in life processes, and which are a basic material in living organisms. Haemoglobin is a component of the red blood corpuscles. It contains iron which can take up oxygen in the lungs and later give it up to the body's other tissues. Haemoglobin is counted among the globular proteins, whose molecules are nearly spherical. It was chosen for the initial attempt, partly because it could develop good crystals, and partly because the haemoglobin molecule is quite small for a protein molecule. About ten years later, John Kendrew joined Perutz' research group, and the task allotted to him was to try to determine the structure of myoglobin. Myoglobin is another globular protein, closely related to haemoglobin, but with a molecule only a quarter as large. It is found in the muscles, and enables oxygen to be stored there. Particularly large amounts of myoglobin are found in the muscular tissues of whales and seals, which need to be able to store large quantities of oxygen when diving.

However, Perutz and Kendrew encountered considerable difficulties. In spite of exceptionally comprehensive work, the result was not forthcoming until 1953, when Perutz succeeded in incorporating heavy atoms, namely those of mercury, into definite positions in the haemoglobin molecule. By this means the diffraction pattern is altered to some extent, and the changes can be utilized in a more direct structure determination. The method was already known in principle, but Perutz applied it in a new way, and with great skill. Kendrew also succeeded, by an alternative method, in incorporating heavy atoms, generally mercury or gold, into the myoglobin molecule, and could subsequently proceed in an analogous manner.

A necessary condition for this technique is that the addition of the heavy atoms should not alter the positions of the other atoms of the molecule within the crystal. In this connection it is simply because of its enormous dimensions that the molecule remains practically unaltered. Bragg has rather aptly said that "the molecule takes no more notice of such an insignificant attachment than a maharaja's elephant would of the gold star painted on its forehead".

But even if the path was now open for a direct structure determination of haemoglobin and myoglobin, there was still an enormous amount of data to be processed. Myoglobin, the smaller of the two molecules, contains about 2,600 atoms, and the positions of most of these are now known. But for this purpose, Kendrew had to examine 110 crystals and measure the intensities of about 250,000 X-ray reflections. The calculations would not have been practicable if he had not had access to a very large electronic computer. The haemoglobin molecule is four times as large, and its structure is known less thoroughly. In both cases, however, Kendrew and Perutz are currently collecting and processing an even greater number of reflections in order to obtain a more detailed picture.

As a result of Kendrew's and Perutz' contributions it is thus becoming possible to see the principles behind the construction of globular proteins. The goal has been reached after twenty-five years' labour, and initially with only modest results. We therefore admire the two scientists not only for the ingenuity and skill with which they have carried out their work, but also for their patience and perseverance, which have overcome the difficulties which initially seemed insuperable. We now know that the structure of proteins can be determined, and it is certain that a number of new determinations will soon be carried out, perhaps chicfly following the lines which Perutz and Kendrew have indicated. It is fairly certain that the knowledge which will thus be gained of these substances which are so essential to living organisms will mean a big step forward in the understanding of life processes. It is thus abundantly clear that this year's prize-winners in chemistry have fulfilled the condition which Alfred Nobel laid down in his will, they have conferred the greatest benefit on mankind.

Doctor Kendrew and Doctor Perutz. One of you recently said that today's students of the living organism do indeed stand on the threshold of a new world. You have both contributed very efficiently to the opening of the door to this new world and you have been among the first to obtain a glimpse of it. Through your combined efforts there is now in view, as it has been stated by yourself, a firm basis for an understanding of the enormous complexities of structure, of biogenesis and of the functions of living organisms both in health and disease.

It is with great satisfaction, therefore, that the Royal Swedish Academy of Sciences has decided to award you this year's Nobel Prize for Chemistry for your brilliant achievement.

On behalf of the Academy I wish to extend to you our heartiest congratulations, and now ask you to receive from the hands of His Majesty the King the Nobel Prize for Chemistry for the year 1962.

The figures are taken from A Little Ancient History by Richard (Dick) Dickerson. The top figure shows the myoglobin/hemoglobin group outside the New Cavendish Laboratory in 1958. That's Maz Perutz in the white lab coat. The second picture is a remarkable photograph of two postdocs, Bror Strandberg (back) and Dick Dickerson (front) carrying the paper tapes for the myoglobin 2A data set. They are just outside the EDSAC II computing centre.

Hemoglobin

 
The following text is slightly modified from Horton et al. (2007) Principles of Biochemistry.

In vertebrates, O₂ is bound to molecules of hemoglobin for transport in red blood cells, or erythrocytes. Viewed under a microscope, a mature mammalian erythrocyte is a biconcave disk that lacks a nucleus or other internal membrane-enclosed compartments (right). A typical human erythrocyte is filled with
approximately 3 × 10⁸ hemoglobin molecules.

Hemoglobin is more complex than myoglobin because it is a multisubunit protein. In adult mammals, hemoglobin contains two different globin subunits called α-globin and β-globin. Hemoglobin is an α₂β₂ tetramer, which indicates that it contains two α chains and two β chains. Each of these globin subunits is similar in structure and sequence to myoglobin, reflecting their evolution from a common ancestral globin gene in primitive chordates.


Each of the four globin chains contains a heme prosthetic group identical to that found in myoglobin. The α and β chains face each other across a central cavity (above). The tertiary structure of each of the four chains is almost identical to that of myoglobin (left). The α chain has seven helices, and the β chain has eight. (Two short α helices found in β-globin and myoglobin are fused into one larger one in α-globin.) Hemoglobin, however, is not simply a tetramer of myoglobin molecules. Each α chain interacts extensively with a β chain, so hemoglobin is actually a dimer of αβ subunits. The presence of multiple subunits is responsible for oxygen-binding properties that are not possible with single-chain myoglobin.

The structure of hemoglobin was solved by Max Perutz [Nobel Laureates].



©Laurence A. Moran and Pearson Prentice Hall 2007

Myoglobin

 
Myoglobin is the simplest type of oxygen carrying molecule in vertebrates. It consists of a single polypeptide chain bound to a heme group. The example shown on the left is sperm whale myoglobin. It shows the heme group edge on (gray) bound to a molecule of oxygen (red balls in the middle of the heme group on the right). The other oxygens, left and top, are part of the heme molecule.

The oxygen is bound to the iron atom at the center of the heme group. In the absence of oxygen this iron atom interacts with the side chains of two histidine residues in the myoglobin polypeptide chain. When oxygen binds it forms a bridge between one of the histidine residues (His-64) and the iron atom in the heme group.

Although the oxygen molecule is tightly bound in this configuration it is still capable of being released under the right conditions. Those conditions can be found inside cells that have become depleted in oxygen. Myoglobin is usually found in muscle cells in vertebrates where it plays a role in storing oxygen. The structure of myoglobin was determined by John Kendrew [Nobel Laureates].

Myoglobin is a member of a large family of globins. They include hemoglobin and similar oxygen carrying molecules in bacteria, plants, and other animals. The myoglobins have evolved from ancestral globins to specialize in oxygen storage inside cells.

©Laurence A. Moran and Pearson Prentice Hall 2007

Heme Groups

 
Monday's Molecule #37 is the heme group found in myoglobin and hemoglobin. The heme group consists of a ring structure, called a tetrapyrrole ring system, complexed to a central iron atom. There are many different kinds of these tetrapyrrole structures in cells. They are distinguished by slight changes in the chemistry of the ring system. This particular structure (left) is called protoporphyrin IX. The structure was originally determined by Hans Fischer [Nobel Laureate: Hans Fischer],

The red color of blood is due to the presence of the heme group, which absorbs visible light. Note that the pyrrole rings are linked by methene bridges (-CH=) to create a conjugated double bond system where electrons can be shared all across the ring. Not only does this mean that these rings can absorb photons, it also means that they can accommodate additional electrons without too much trouble.

This is why there are many heme proteins that are involved in oxidation-reduction reactions (reactions that transfer electrons from one substrate to another). For example, cytochrome c has a similar kind of heme group (right). Cytochrome c is a major player in membrane associated electron transport systems in bacteria and mitochondria and in photosynthesis.

Heme type molecules are always tightly bound to proteins. Such molecules are called prosthetic groups and there are two types. The heme in hemoglobin is bound by many weak interactions such as hydrogen bonds and van der Waals interactions. The heme in cytochrome c is an example of a covalently bound prosthetic group. It is attached to its protein by bonds between the edge of the porphyrin ring and cysteine (Cys) side chains in the protein.

Chlorophyll (left) is another type of tetrapyrrole ring molecule but it differs from most others because the central chelated metal ion is magnesium (Mg) instead of iron. Chlorophyll molecules absorb light very efficiently and that's why they play such an important role in photosynthesis. Photosynthesizing organisms—bacteria, algae, plants—have dozens (or hundreds) of chlorohyll molecules packed in their membranes.


©Laurence A. Moran and Pearson Prentice Hall 2007

Physicians Are "Science Professionals"

 
At least that's what the IDiots say [Medical Doctors a Fast Growing Segment of Darwin Doubting Science Professionals].

Who knew? I suppose we shouldn't be surprised if they think an M.D. degree makes you a "science professional." After all, these are some of the same people who think the Earth is only 10,000 years old.

UPDATE: Turns out that many of these medical doctors are actually dentists [Dentists Against Darwin]. Sheesh!

Your View of Evolution

 
The poll for August asks you to identify the person who comes closest to representing your view of evolution. Check out the left hand margin.

70% of Sandwalk Readers are Atheists

 
According to the latest poll (see left hand margin) 70% of Sandwalk readers are atheists (PZ would be proud.). 12% are agnostics—I guess Wilkins and Catshark figured out how to vote multiple times. Only 14% are believers. I wish there were more believers, it would make for more lively discussions.

Six of you are uncertain. Why?

Another Bad Review of The Edge of Evolution

PZ Myers draws attention to another review of Michael Behe's new book The Edge of Evolution [Behe gets another thumbs-down]. This review is published in the July issue Discover magazine [The Simplistic Manifesto]. The author is Cory S. Powell.

I disagree with PZ. This is not a good review. Actually, it's a very bad review. Like many of the published reviews of The Edge of Evolution the author seems to have been reading a far different book than the one I read. Powell says,

To reach this conclusion, Behe makes a number of invalid assumptions about how molecules evolve and interact. He alleges that, because many functional adaptations require multiple changes in proteins, two or more mutations must occur together at the same time in the same gene and only rarely can several mutations "sequentially add to each other to improve an organism’s chances of survival." But in fact natural selection does work on transitional forms, as molecules and traits evolve stepwise. Stepwise evolution has been well documented; one good instance of this is the emergence of color vision. Mutations add up little by little, leading to major changes to proteins over time.

The essence of Behe's argument is not that it's impossible to evolve a double mutation if each one is beneficial. The whole point of the book is that stepwise evolution requires that each step is beneficial. The evidence, according to Behe, shows that many cases involving double mutations involve intermediates that are disadvantagous. Thus, the double mutant had to arise in a single step and this is highly unlikely.

Behe isn't always as clear as he should be but he does make it perfectly clear that he accepts the mechanism that Powell describes. Thus, Powells' criticism is inappropriate and this makes it a bad review. Apparently Powell didn't read the section on the evolution of antifreeze proteins in fish (pp. 77-81) where Behe describes each of the many steps that lead to the modern antifreeze proteins.

Each step would have given the fish some protection against freezing water. Thus, Behe concludes,

Even though we haven't directly observed it, the scenario seems pretty convincing as an example of Darwinian evolution by natural selection. It's convincing because each of the steps is tiny&mdash'no bigger than the step that yielded the sickle cell mutation n humans—and each step is an improvement.

The Discovery review points out that complex combinations of mutations can arise in a stepwise manner by standard Darwinian mechanisms. It implies that Behe never thought of this in his book but that's total nonsense. Of course he did. Behe doesn't deny that phenotypes requiring multiple steps can be produced by random mutations, as long as each step is beneficial. The essence of his argument is that it's impossible to generate phenotypes that require multiple random mutations if the intermediates aren't beneficial.

I'm not arguing that Behe is correct. In fact, I'm preparing a series of postings that will challenge some of his ideas. What I'm objecting to is the mischaracterization of Behe's arguments in many of the published reviews. If you're going to criticize Behe then challenge the argument he makes in the book; namely, that most stepwise pathways are impossible because the intermediates are less fit than their parents.

Powell makes another common mistake in his review. He says,

Behe makes another big, related error in the way he interprets how proteins work together. He contends that for even three proteins to evolve in a cooperative association is wildly improbable, "beyond the edge of evolution." Within a protein, five or six amino acids (components of proteins) need to change simultaneously for it to bond with another protein, according to Behe. From this he concludes that it is impossible for proteins’ interaction to evolve, again requiring life to have been programmed for success from the start. Plenty of evidence contradicts this assertion, however. Many proteins within cells interact with other proteins in ways in which only two or three amino acids are critical for binding.

Behe admits that you may only need three or four selected changes in order to generate a new binding site (p. 114). He agrees that the evolution of a single binding site is within reach of evolution but the simultaneous generation of two binding sites is beyond the edge of evolution because the probabilities are so low. The point is that there are many complexes that require the interaction of several different proteins and the intermediates—where only two proteins interact—are not beneficial. Refuting Behe's real arguments requires a little more effort than the superficial criticism of arguments that Behe is not making.

Powell continues,

Such simple binding sites can arise frequently in proteins. And such interactions form the networks that regulate all sorts of physiological processes in cells and organisms. Cell biologists and biochemists are increasingly finding that, in truth, protein interactions and networks are easy to evolve. Behe should know this—but he has a long history of alleging evolutionary impossibilities and ignoring the scientific literature.

Powell is completely missing the point here. Behe does not deny that such complexes exist, nor does he deny that they evolved in the sense that they arose in organisms whose ancestors didn't have them. Once the mutations occurred, they became fixed in the population by natural selection. Furthermore, Behe does not deny that these networks are "easy to evolve." In fact, they are so "easy to evolve" that they cannot be explained by natural selection acting on random mutations as "Darwinism" requires. Thus, mutations cannot be random.

You don't refute Behe by pointing to examples of evolution by common descent or natural selection; this includes evolution of protein complexes. That's not the point. The point is that "Darwinian" evolution, according to Behe, must require small steps where each step is beneficial and this cannot be demonstrated. Indeed, in many cases the intermediates will likely be detrimental. The conclusion is that multiple mutations have to occur simultaneously as in some drug resistance. For most populations the probability of this happening by random mutation is very small. The fact that it happened is evidence of directed mutation, or so Behe thinks.

In order to show that Behe is wrong you have to demonstrate that his understanding of evolution (i.e., "Darwinism") is wrong and this has led him to false conclusions about probabilities. Many reviewers have failed to do this, possibly because they accept Behe's version of Darwinism.

You can read Michael Behe's responses to his reviewers on the Amazon.com site [Michael Behe's Amazon Blog]. I think it's fair to say that Behe makes some good points (and many bad ones) when he accuses his reviewers of misrepresentation.

Virtual Toronto

 
Here's a site that combines an interactive map of Toronto with images from selected streets [Toronto Virtual City]. The photograph (left) shows the entrance to my building on the University of Toronto campus. The view is looking north from College St.

The satellite view is about two years old. It was taken when the new building was still under construction so the street level image doesn't match the satellite view.

Hmmm ... that reminds me. How come we don't see any more postings where we have to identify a university campus? I forgot which blog that was on.

[Hat Tip: Monado]

Gene Genie #12

 


Gene Genie #12 has been posted at My Biotech Life [Gene Genie #12 aka The Dozen].

The image is from the article on snpedia [WikiPedia Meets Genetics]. Read about how you can access the personal genome of Jim Watson and Craig Ventor.

Monday's Molecule #37

 
Today's molecule looks complicated but it has a very simple name. The short common name of this molecule is not sufficient—you have to supply the correct biochemical name that distinguishes this molecule from similar ones found inside all cells. You're more than welcome to supply the complete IUPAC name if you know it.

There's an indirect connection between this Monday's Molecule and Wednesday's Nobel Laureate(s).

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

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

Canadian Dinosaur Coins

 
The Royal Canadian Mint has dinosaur coins for sale. Here's a picture of the first one. It shows a fossil Parasaurolophus, a crested, duck-billed species from Alberta.

Future coins will depict Triceratops (2009); Tyrannosaurus rex (2009); and Dromaeosaurus (2010). The face value of the coins is $4 (CDN)—that's currently about $3.80 in US currency but it will be about $4.60 by the time the last coin is issued unless the US dollar stops falling. (Getting out of Iraq would help.)

Only 20,000 coins are being minted. The finish on the "fossil" image is impossible to reproduce exactly so each coin will be slightly different in tone and color. You can buy them for $39.95 (CDN).

How many people know what "D.G. Regina" stands for? (Hint: it's not an atheist slogan.)

The OUT Campaign

 
RichardDawkin.net has started something called the The OUT Campaign. The goal is to encourage all non-believers (atheists) to come out of the closet and make their rejection of religious superstition known. You're supposed to use the red "A" as a symbol to declare that you are an atheist. Several bloggers have put it on their website.

I do not believe in God. I am an atheist. However, the fact that I don't believe in something is often the only thing I have in common with other atheists. It seems a bit silly to form a club based only on what you don't believe in. It would be like having a club for everyone who doesn't believe in Bigfoot, or Santa Claus.

So, while I am happy to announce my preference for rationalism over superstition and proud to be an atheist. I won't be joining any organization based on a negative. I am a proud member of Skeptics Canada and The Centre for Inquiry, Toronto because they stand for something positive.

[Hat Tip: PZ Myers]

The Aliens Are Coming

 
Friday's Urban Legend: False

			The following email message is going the rounds. ALIENS ARE COMING TO ABDUCT ALL THE GOOD LOOKING AND SEXY PEOPLE. YOU WILL BE SAFE, I'M JUST EMAILING TO SAY GOODBYE. We know it's false because I'm still here.

Theme: Deoxyribonucleic Acid (DNA)

 
THEME

Deoxyribonucleic Acid (DNA)

1. Wellcome Trust Images


2. A Strange Molecule


3. Monday's Molecule #35 (ethidium)


4. DNA Is a Polynucleotide


5. Tautomers of Adenine, Cytosine, Guanine, and Thymine


6. Nucleotides Can Adopt Many Different Conformations


7. Nobel Laureates: Francis Crick, James Watson, and Maurice Wilkins


8. The Chemical Structure of Double-Stranded DNA


9. The Three-Dimensional Structure of DNA


10. The Story of DNA (Part 1) Where Rosalind Franklin Teaches Jim and Francis Something about Basic Chemistry


11. Ethidium Bromide Binds to DNA


12. Rosalind Franklin Announces the Death of the Helix


13. Nobel Laureates 1962


14. The Story of DNA (Part 2)Where Jim and Francis Discover the Secret of Life


15. DNA With Parallel Strands


16. Measuring Stacking Interactions


17. Are You as Smart as a Third Year University Student?


18. Rosalind Franklin's Birthday


19. The Watson & Crick Nature Paper (1953)


20. The Franklin & Gosling Nature Paper (1953)


21. The Wilkins, Stokes and Wilson Nature paper (1953)


22. Ethidium Bromide Is a Dangerous Chemical


23. Jim Watson on the Discovery of the Double Helix


24. DNA Tatoo


25. DNA Polymerase I and the Synthesis of Okazaki Fragments


26. Play the DNA Double Helix Game

The Wilkins, Stokes and Wilson Nature paper (1953)

Wilkins published his work on the structure of DNA in the same issue of Nature as the Watson & Crick paper and the Franklin & Gosling paper. The coauthors on the wilkins paper were A.R. Stokes and H.R. Wilson. They were reunited in 1993 on the 40th anniversary of the publication as shown in the photo. (From left to right: Raymond Gosling, Herbert Wilson, Maurice Wilkins and Alec Stokes.)

A copy of the Wilkins, Stokes and Wilson paper is here.

The title of the paper "Molecular Structure of Deoxypentose Nucleic Acids" indicates that this is a paper that will discuss details and experimental results. This is a paper that emphasizes the similarities between X-ray diffraction patterns of DNA fibres from calf thymus, wheat germ, herring sperm, human, and T₂ bacteriophage. They also look at DNA in vivo by examining intact sperm heads, bacteriophage, and animal viruses. The authors conclude that all these DNA have the same general structure and that it is consistent with the model proposed by Watson & Crick.

The Franklin & Gosling Nature paper (1953)

Rosalind Franklin and Raymond Gosling published their results on the structure of DNA in a Nature paper that immediately followed the famous Watson & Crick paper [The Watson & Crick Nature Paper (1953)]. Franklin had completed the manuscript before traveling up to Cambridge to see the Watson & Crick model of DNA but she was able to make changes to her paper before submitting it in early April 1953. A PDF of the paper as it appeared in the journal is here and the original manuscript is here.

The title of the paper, "Molecular Configuration in Sodium Thymonucleate," gives us a clue to why this paper has been ignored and the Watson & Crick paper gets all the attention. The Franklin & Gosling paper is full of obscure references and equations and it's significance can only be recognized because of the paper that preceded it in the April 25th, 1953 issue of Nature. The writing style is ponderous and it does not convey any of the sense of excitement found in the Watson & Crick paper [see April 25, 1953: Three papers, three Lessons].

Franklin and Gosling conclude that DNA is "probably helical," the phosphate groups lie on the outside, and there are probably two strands. They state,

Thus our general ideas are not inconsistent with the model proposed by Watson and Crick in the preceding communication.

As is the case in the Watson & Crick paper, papers in the same issue of the journal are not specifically referenced. If you follow the link to the typed manuscript (above) you can see that this sentence was inserted by hand.

Franklin & Gosling acknowledge their colleagues at the end of the paper in the same manner we saw in the Watson & Crick paper.

We are grateful to Prof. J.T. Randall for his interest and to Drs. F.H.C. Crick, A.R. Stokes, and M.H.F. Wilkins for discussion.