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]