DNA Replication in E. coli: The Problem

I've started reading microcosm by my favorite science writer, Carl Zimmer [Buy This Book!]. Watch for a review, coming soon.

I was mildly disappointed to see Carl repeat a common myth about DNA replication in E. coli on page 29. Since we often use this myth to teach critical thinking in our undergraduate classes, I thought it would be worthwhile to discuss it here.

Today I'm going to present the problem and let everyone think about a possible solution. On Sunday, I'll publish the answer. (If you know the solution, you are not allowed to post it in the comments—I'll delete those comments. You can ask for clarification or speculate.)

Here's what Carl says at the top of page 29.

E. coli faces a far bigger challenge to its order when it reproduces. To reproduce, it must create a copy of its DNA, pull those chromosomes to either end of its interior, and slice itself in half. Yet E. coli can do all of that with almost perfect accuracy in as little as twenty minutes.

Today, we're not concerned about the 20 minute generation time but I note, for the record, that the average generation time of E. coli, in vivo, is about one day. I also want to mention that the 20 minute generation time is an extreme example that's achieved only under the most extraordinary circumstances. Typical generation times in the lab are about 30 minutes.

However, that's not the problem. Let's assume a generation time of 20 minutes.

In the next paragraph Carl says ...

The first step in building a new E. coli—copying more than a million base pairs of DNA—begins when two dozen different kinds of enzymes swoop down on a single spot along E. coli's chromosome. Some of them pull the two strands of DNA apart while others grip the strands to prevent them from twisting away or collapsing back on each other. Two squadrons of enzymes begin marching down each strand, grabbing loose molecules to build it a partner. The squadrons can add a thousand new bases to a strand every second.

What Carl is referring to the the assembly of replication complexes (replisomes) at the origin of replication. Once those complexes are assembled, replication fires off and proceeds in opposite directions (bidirectionally) until the two fork meet at the opposite side of the chromosome.



Carl is correct when he says that the forks move at 1000 nucleotides per second. Later on in his book he mentions that the size of the E. coli chromosome is 4,600,000 base pairs or 4,600 kb (p. 116). At 1000 nucs per second it would take 4600 second to replicate this DNA if there was only one replication fork. Since there are two, it will take 2,300 seconds.

You can do the math. This is 38 minutes. It is a correct number—it takes at least 38 minutes to replicate the E. coli chromosome, not 20 minutes as stated earlier. It is true that the generation time of E. coli can be as short as 20 minutes under extraordinary circumstances.

Here's the problem. How can E. coli divide faster than it can replicate it's chromosome?

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Ben Stein's Dangerous Idea

 
Uncommon Descent is the Intelligent Design blog of Bill Dembski, Denyse O'Leary and their friends. It represent the best that the IDiots have to offer.

Yesterday's posting by DLH is an example of the best sort of creationist reasoning. The posting is an extensive quotation from an article by Robert Meyer originally posted in New Alliance Magazine [Ben Stein’s Dangerous Idea]. Here are the first three paragraphs quoted on the blog ...

Ben Stein has a dangerous idea. His idea is that professors and teachers who express skepticism about Darwinism are likely to find themselves not granted tenure, castigated and ridiculed, and disqualified from the opportunity to have research papers published.
. . .
Having reviewed the movie myself, it appeared that Stein was trying to make the case for academic freedom, not attempted to convert anyone to a particular ideological position.

Stein, in fact, never makes it known what particular beliefs he holds personally, he merely makes it known that he is disgusted by the idea that someone could lose their job over honest doubts about Darwinism.

No, your eyes are not deceiving you. Re-read that last paragraph. For all we know Stein may be a secret evolutionist. He's only interested in academic freedom. It's just a coincidence that the phrase "No Intelligence Allowed" uses the same word as Intelligent Design.

Jeesh. And you wonder why we call them IDiots?

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Make Englishe the Only Offal Language

 
I'm with Orac and Orcinus on this one. This is just too delicious to resist.¹

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1. Although, as a notoriously bad speller, I have made some pretty similar mistakes on Sandwalk.

Congratulations Jason Rosenhouse!!!

 
A big event just happened at Evolutionblog—Jason Rosenhouse got tenure [Tenure!]. Congratulations Jason.

I'll let him describe the process ....

I got tenure! Yay! By my count it's been about fifteen years getting to this point. I started studying mathematics seriously in my last two years of college (a rather late start in this profession). Then it was five years of graduate school, three years as a post-doc in Kansas, and now five years at JMU. Pretty satisfying. Suddenly that obnoxious and contentless rejection letter I received a month ago on a paper the journal should have been honored to publish doesn't seem to sting so much. (I'll just patch it up and send it off to the next journal, where it will languish for ten months to a year. What do I care? It's not like I'm in any great hurry to publish anymore!)

So there you go. Guess now I can tell you what I really think...

I guess this is when we discover that Jason is really a closet IDiot.

UPDATE: It didn't take long ...

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Nobel Laureates: Arvid Carlsson and Paul Greengard

 

The Nobel Prize in Physiology or Medicine 2000.

"for their discoveries concerning signal transduction in the nervous system"

Arvid Carlsson (1923 - ) and Paul Greengard (1953 - ) received the Nobel Prize in Physiology or Medicine for their work on identifying dopamine as a neurotransmitter. They also showed that L-dopa [Monday's Molecule #70], a precursor of dopamine, could relieve the symptoms of dopamine depletion and help control the symptoms of Parkinson's disease. They shared the prize that year with Eric R. Kandel.

THEME:Nobel LaureatesThe presentation speech was given by Professor Urban Ungerstedt of the Nobel Committee at Karolinska Institutet. (The date was, of course, December 10th as always. This is the anniversary of Alfred Nobel's death.)

Your Majesties, Your Royal Highnesses, Ladies and Gentlemen,

This year's Nobel Prize in Physiology or Medicine concerns the most complex structure in the universe that we know of - the human brain. It consists of 100 billion nerve cells, which is the same number of cells as the total number of human beings that have ever lived on this earth.

We talk about the "Internet revolution"; 35 million Internet users who communicate now and then - what is that compared to the nerve cells we all carry within ourselves! 100 billion nerve cells that communicate continuously.

It is this communication, "signal transduction in the nervous system," which is the subject of this year's Nobel Prize. A single nerve cell forms thousands of contact points, so-called synapses, with other nerve cells. In these synapses the nerve cells communicate by chemistry; one cell releases a transmitter, which reaches the other cell.

Professor Arvid Carlsson proved that dopamine is such a transmitter. The general belief was that dopamine was a precursor of other transmitters and of little functional importance. However, Professor Carlsson was able to show that dopamine existed in specific parts of the brain and concluded that it was a transmitter in its own right.

He then used a naturally occurring substance, reserpine, which empties the dopamine from the nerves, and found that the animals lost their ability to move. He realized that it must be possible to restore the dopamine levels with L-DOPA, a precursor of dopamine. In a conclusive, dramatic experiment he showed that the animals regained their ability to move when he gave them L-DOPA.

Reserpine had depleted dopamine and had given the animals the symptoms of Parkinson's disease, that is, rigidity and inability to move and react to stimuli in the environment. When the animals were given L-DOPA, dopamine was produced again in their brains. In this way the idea of treating Parkinson patients with L-DOPA was born. This enables millions of patients around the world to live a normal life.

Professor Paul Greengard showed what happens when dopamine and other similar transmitters stimulate a nerve cell. Receptors on the cell surface activate enzymes in the cell wall, which starts the production of second messengers. These messengers travel into the cell and activate a protein kinase, which starts to bind phosphate groups to other proteins, in this way altering their function. This leads, for example, to the opening of ion channels in the cell membrane and a change in the electrical activity of the cell.

Professor Greengard then showed that dopamine and other transmitters affect a central regulatory protein, which has been called DARPP-32. Like the conductor of an orchestra, it tells other proteins when and how to be activated.

This so-called "slow synaptic transmission" controls our movements and also those processes in the brain that elicit emotions or react to addictive drugs such as cocaine, amphetamine and heroin.

Professor Eric Kandel showed that transmitters of the same type as studied by Arvid Carlsson, via the protein kinases characterized by Paul Greengard, are involved in the most advanced functions of the nervous system such as the ability to form memories.

Imagine how difficult or impossible it must be to study how memory is formed in a human brain with 100 billion nerve cells. Eric Kandel, therefore, did something which is classical in all natural science: He chose to study a simpler model system, a sea slug, Aplysia, which has 20,000 nerve cells. He did it with the conviction that even primitive animals must learn in order to survive.

The sea slug has a withdrawal reflex protecting its gills. If they are touched repeatedly, they react less and less - just as human beings do when subjected to an unexpected touch. If, on the other hand, the touch is forceful the reflex is amplified and becomes stronger and stronger.

The habituation or amplification effect lasts only for a few minutes. One may say that the sea slug exhibits a short-term memory. If the forceful stimulus is repeated several times, the sensitization may remain for weeks, that is, the sea slug develops a long-term memory.

Professor Kandel was able to show that habituation to touching was due to changes in the synapse, the contact point between the nerve cells. During habituation less and less transmitter was released.

The forceful stimulus that formed the long-term memory worked in a completely different way. Second messengers activated protein kinases that entered the cell nucleus and started the production of new proteins. This, in turn, brought about a change in the form and function of the synapse. What we call memory is, thus, elicited by direct changes in the billion of synapses that form the contact points between the nerve cells.

I am convinced that you and I will remember this Nobel ceremony for many years. This is because of the dopamine which Arvid Carlsson discovered, enabling the brain to react to what we see and hear; the second messengers that Paul Greengard described, carrying the signals into the nerve cell; and the memory functions that Eric Kandel found to be due to changes in the very form and function of the synapses.

Dear Arvid Carlsson, Paul Greengard and Eric Kandel. Your discoveries concerning "signal transduction in the nervous system" have truly changed our understanding of brain function. From Arvid Carlsson's research we now know that Parkinson's disease is due to failure in synaptic release of dopamine. We know that we can substitute the lost function by a simple molecule, L-DOPA, which replenishes the emptied stores of dopamine and in this way, give millions of humans a better life.

We know from Paul Greengard's work how this is brought about. How second messengers activate protein kinases leading to changes in cellular reactions. We begin to see how phosphorylation plays a central part in the very orchestration of the different transmitter inputs to the nerve cells.

Finally, Eric Kandel's work has shown us how these transmitters, through second transmitters and protein phosphorylation, create short- and long-term memory, forming the very basis for our ability to exist and interact meaningfully in our world.

On behalf of the Nobel Assembly at Karolinska Institutet, I wish to convey our warmest congratulations and I ask you to step forward to receive the Nobel Prize from the hands of His Majesty the King.

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[Photo Credits: The photo of Arvid Carlsson celebrating is from "The Nobel Prize did change my life!" . The photo of Paul Greengard with his wife Ursala von Rydingsvard is from The New York Times. Greengard used his prize money to fund an annual $50,000 award to an outstanding female medical researcher.

Healing Through Quantum Mechanics

 
Jeffrey Shallit at Recursivity posts about a chiropractor in Seattle who will heal you by using quantum mechanics [Your Daily Dose of Woo].

There's a comment on his blog that points to a quack right there in Kitchener/Waterloo who makes the same silly claims. Check it out. I've inserted a picture of the ECLOSION (Electro Physiological Feedback Xrroid) device from the Kuantum Power website. Wouldn't you just love to have one of those? It will even work on computers made by fruit companies.

These are more examples of the misuse of science. How can we combat this except by making sure we educate students properly? Judging by what I see at the University of Toronto, we aren't doing a very good job of teaching students how to think. I get the feeling that most of my colleagues aren't aware of the problem and those that are, don't care. I see lots of similar woo in the scientific literature.

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Misusing Science

 
Canadian Cynic has a new job that forces him to drive past a certain billboard every day [And now, two troublemakers that need no introduction ...].

CC links to the website of the billboard sponsor [Stop the Cover-up]. Here's what you see if you follow the link.


This is group of people who are opposed abortion. What they're saying is that women who choose abortion are more likely to get breast cancer. Specifically ...

It is a well established fact that abortion can increase a woman’s risk of developing breast cancer by denying her the protective effect of both a full-term pregnancy as well as breast-feeding. In addition, the abrupt, artificial termination of a healthy pregnancy leaves a woman with an increased number of vulnerable undifferentiated (immature) breast cells which are, in turn, exposed to the massive amounts of estrogen present during early normal pregnancy. Estrogen is a known cancer causing hormone.

Now, it doesn't take too much exposure to real science to recognize the problem with such claims. What they're doing is taking a little bit of truth and distorting it into something that's not the truth.

This sort of thing is very common these days. Everyone wants to bask in the glow of science even when they are doing their best to extinguish that glow. Everyone wants to have their cake and eat it too.

I hate to bring up the framing issue again but, at the risk of sounding like a broken record, this ad is exactly the sort of thing I fear when Nisbet and Mooney start preaching. There's no question in my mind that this ad is a good example of framing (=spin). I'm not sure how we distinguish between this approach and one were we all agree to use science to support certain policies on climate change, or certain approaches to dealing with creationism.

At what point do we draw the line between truth and lies? Who is going to be the judge of when that line is crossed?

UPDATE: Abortion and Breast Cancer: There Is no Link.

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You're Not Gonna Believe This ...

 

According to Bill Dembski [Who’s in it for the money?].

Darwinism has always been an upper-class movement. ID, by contrast, is strictly middle-class. That’s our base and that’s where we find our support.

You won't believe his evidence for such a statement unless you actually follow the link and read what he wrote.

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Atheists in the Media

 
Come to the Centre for Inquiry's lecture by Wodek Szemberg on the role of atheists in the media. [Why So Few Atheists in the Media?].

Email me if you'd like to attend. Maybe we could meet at my office and get together for something to eat before walking to the Centre for Inquiry on Beverley St.? I'm certainly going to ask him about the "Best Lecturer" series. That should be fun.

SPECIAL EVENT: Why So Few Atheists in the Media? with TVO The Agenda Producer

Starts
Friday, May 9th at 7:00 pm
Ends
Friday, May 9th at 9:00 pm
Location
Centre for Inquiry Ontario, 216 Beverley St., Toronto, ON M5T 1Z3, 1 minute south of College St. at St. George St.

Wonder why secular humanists aren't included on every media ethics panel which includes the perspectives of just about everyone else?

INFLUENTIAL TV PRODUCER DISCUSSES ATHEIST & HUMANIST MARGINALIZATION IN THE MEDIA AND SUGGEST NEW STRATEGIES

Special FREE Event!

Featuring Wodek Szemberg, TV Ontario Producer of The Agenda with Steve Paiken, Best Lecturer Competition and BIG IDEAS, and "out of the closet" atheist.

Everyone is welcome.

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Skepticast #145: Should Biology Students Pass the Course If They Don't Understand the Science?

 
Steven Novella (photo) is a skeptic and a neurologist at Yale University School of Medicine. He publishes a podcast called Skeptics Guide to the Universe. In the April 30th edition he discusses the proposed Florida Laws on "Academic Freedom" with Bob Novella, Evan Bernstein, and Jay Novella [Skepticast #145].

About one quarter of the way into the podcast they turn their attention to the issue of educating creationists at university. They discuss my views on the subject as described in Do Fundamentalist Christians Actively Resist Learning?. Here's what I said ...

Keeping all these cautions in mind, it is still quite remarkable that some significant percentage of fundamentalist Protestants can go to college and still reject the basic scientific fact that humans evolved. Note that in all of the other groups the college educated subset are more inclined to accept evolution. (Do most of those "college" educated fundamentalists go to some cheap reproduction of a college run by a religious organization?)

As we've seen time and time again on the blogs (and elsewhere), the Christian fundamentalists have erected very strong barriers against learning. It really doesn't matter how much they are exposed to rational thinking and basic scientific evidence. They still refuse to listen.

This is one of the reasons why I would flunk them if they took biology and still rejected the core scientific principles. It's not good enough to just be able to mouth the "acceptable" version of the truth that the Professor wants. You actually have to open your mind to the possibility that science is correct and get an education. That's what university is all about.

Of course, we all recognize the problem here. How do you distinguish between a good Christian who is lying for Jesus and one who has actually come to understand science? It seems really unfair to flunk the honest students who admit that they still reject science and pass the dishonest ones who hide their true beliefs.

I stand by this statement.

Let's take a simple example. Imagine that you are teaching a course in history and you assign readings about the holocaust. On the exam you ask students to describe the history of Nazi occupied areas of Europe from 1940-1945. Imagine that a student describes all of the historical facts that you have taught in class but then rejects them by denying that the holocaust ever happened. The student claims that belief in the holocaust goes against the student's religious convictions. Should the student be given a passing grade in order to avoid discriminating against religious beliefs?

What if you are a Professor of Medicine at Yale University? Imagine teaching a course on basic neurology and the treatment of, say, Parkinson's disease. What would you do about Scientology students who can recite correctly all of the data on effective drug treatment but then reject it all because it conflicts with their religion? Should they still get an M.D. degree? Is evidence based medicine a requirement or can it be sacrificed when it conflicts with sincerely held beliefs?

Imagine that you are teaching a geology class and as part of the exam you ask students to give the age of the Earth and explain the evidence supporting that age. Let's say a student describes the radiometic data correctly but then goes on to reject the 4.5 billion year old Earth because it conflicts with the Bible. This student insists that the Earth is less than 10,000 years old in spite of the scientific evidence. Should that student get a passing grade on the exam on the grounds that flunking them would be religious discrimination?

I'm sure you can make up similar scenarios involving the common ancestry of humans and other apes.

Here's the question. We flunk students who cannot demonstrate that they understand the material and the scientific facts. Should we make an exception for those students who claim that their ignorance is part of their religion?

Listen to the debate between Steven Novella and his friends. Part of the problem is their concept of what "understanding" the material really means. They think that as long as you can correctly regurgitate the words of the textbook then you have demonstrated understanding. That should be sufficient to pass the course. Do you agree with them?

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{Hat Tip: BigHeathenMike]

Reserpine

Reserpine is a powerful plant alkaloid that used to be used to control psychotic behavior and treat certain cancers. Unfortunately, it's severe side effects and unpredictable behavior has limited it's usefulness. The drug has been replaced by more reliable treatments.

Many plants contain mildly toxic alkaloids but in most cases the concentrations are not high enough to cause a problem.¹ Reserpine is concentrated in Rauwolfia serpentina (Indian snakeroot) and this plant has been used for several thousand years in treating a number of aliments. One of the main effects of reserpine is to block the action of dopamine. This blockage causes symptom's that resemble Parkinson's disease. They can be relieved by treating the patient with L-dopa [Monday's Molecule #70].

My first exposure to research was a summer job (1966) in the lab of George Setterfield at Carleton University in Ottawa (Canada). The project was to identify crystal-like inclusions in the cells of Rauwolfia serpentina. The hypothesis was that these inclusions were composed of alkaloids, especially reserpine. As I recall, I didn't make much progress. The inclusions weren't always visible and my suspicion was that they could have been an artifact of the fixation process.

I haven't been able to find any mentions of plant alkaloid inclusions in the literature. Does anyone know this field?

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1. It's much safer to eat meat.

Terms & Conditions on Nature Network

 
Eva Amsen has an interesting question about how you would fund research if you were in complete control of all the money in the world [see, Would you rather?].

I was all set to post a comment when I realized that I had to sign in to Nature Network in order to do so. That reminded me about the terms and conditions. That's way more hassle than I'm prepared to put up with. I prefer the rough and tumble of unrestricted blogs.

My question is, does anyone else feel this way? What's the future of science blogging? Is it the strictly controlled environment of Nature Networks where the fora are part of a for-profit venture? Or is it the free-for-all environment of some of the other science blogs? Or is it something in between like the relatively unrestricted environment of the blogs run by SEED magazine?

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Monday's Molecule #70

 
It's been a while since you had to identify a molecule and give it's correct IUPAC name so here's a molecule that will give you some practice. First, you should assume that this is the L- form of this molecule and not the D- form. (This isn't obvious from the chemical structure.)

Give the common name of the molecule and the complete IUPAC name.

Identify the two Nobel Laureates who were awarded a Nobel Prize, in the same year, for discovering the fundamental properties of this molecule.

The first person to correctly identify the molecule and name the Nobel Laureates wins a free lunch at the Faculty Club. Previous winners are ineligible for one month from the time they first collected the prize. There are only two ineligible candidates for this week's reward.

THEME:

Nobel Laureates
Send your guess to Sandwalk (sandwalk (at) bioinfo.med.utoronto.ca) and I'll pick the first email message that correctly identifies the molecule and names the Nobel Laureates. Note that I'm not going to repeat Nobel Laureates so you might want to check the list of previous Sandwalk postings.

Correct responses will be posted tomorrow. I may select multiple winners if several people get it right.

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

UPDATE: This week's winner is Maria Altshuler from the University of Toronto. She identified the molecule as L-dopa ((S)-2-amino-3- (3,4-dihydroxyphenyl) propanoic acid) and the Nobel Laureates are Arvid Carlsson and Paul Greengard. Congratulations Maria, you beat out several others who came up with the correct answer. The University of Toronto is thumping all other schools in this contest!¹

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1. That might have something to do with the fact that you have to be in Toronto to collect the prize, ya think? Maybe I should have another prize for people who can't come to Toronto? How about a Tim Horton's gift certificate?

Evolution of Sex & Recombination

 
I've been wondering if John Logsdon was still alive. There have been very few postings on his blog Sex, Genes, & Evoluton. Now we know why. He has been organizing a meeting about Sex in Iowa. (Is that an oxymoron?)

This looks like a very interesting meeting. Most of the key players are going to be there. Looking over the list of speakers makes you realize that the problem of sex is still very complicated. We don't have a consensus on the evolutionary advantages of sex (if any). This is an important point since many on the evolutionist side think otherwise. They believe that the evolutionary advantages of sex have been proven and it's no longer an open question.

I hope we'll hear a summary of the talks once the meeting is over.

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Tangled Bank #104

 
The latest issue of Tangled Bank is #104. It's hosted at Dammit Jim! [Tangled Bank #104].

Welcome to the 104th edition of the Tangled Bank blog carnival (a biweekly showcase of good biology posts selected by the authors themselves). Rigorous calculations and archaelogical research have revealed that this is the Tangled Bank’s 4th birthday. In the birthday spirit, several people sent appropriately themed presents.

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If you want to submit an article to Tangled Bank send an email message to host@tangledbank.net. Be sure to include the words "Tangled Bank" in the subject line. Remember that this carnival only accepts one submission per week from each blogger. For some of you that's going to be a serious problem. You have to pick your best article on biology.