Monday's Molecule #130

 
I thought last week's molecule would be a challenge but Sandwalk readers came up with the correct answer even in the middle of summer in the Northern hemisphere. Considering how well you did last week, following up with this week's "molecule" should be a gift.

Identify the thing shown here and relate it to a Nobel Laureate.

The first person to identify the "molecule" and the Nobel Laureate(s), wins a free lunch. Previous winners are ineligible for six weeks from the time they first won the prize.

There are six ineligible candidates for this week's reward: Bill Chaney of the University of Nebraska, Ian Clarke of New England Biolabs Canada in Pickering ON, Canada. Dima Klenchin of the University of Wisconsin at Madison, Dara Gilbert of the University of Waterloo, Anne Johnson of Ryerson University, and Cody Cobb, soon to be a graduate student at Rutgers University in New Jersey.

I have an extra free lunch for a deserving undergraduate so I'm going to continue to award an additional prize to the first undergraduate student who can accept it. Please indicate in your email message whether you are an undergraduate and whether you can make it for lunch.

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(s) and names the Nobel Laureate(s). Note that I'm not going to repeat Nobel Prizes so you might want to check the list of previous Sandwalk postings by clicking on the link in the theme box.

Correct responses will be posted tomorrow.

Comments will be blocked for 24 hours.

---

The image is from Butan et al. (2008) [doi: 10.1016/j.jmb.2007.12.003]

The Origin of Dachshunds

 
A draft sequence of the dog (Canis lupus familiaris) genome has been available for several years. One of the reasons for working with dog genes and genomes is the fact that there are many different breeds. Since these breeds differ genetically and morphologically, there's a distinct possibility that the genes for various characteristics can be identified by comparing variants from different breeds.

One of the exciting possibilities is that some interesting behavioral genes could be identified since many breeds of dog are loyal, easy to train, and intelligent.¹

In addition to possible behavioral genes, one can identify many genes affecting morphology. One of them is the gene affecting short legs in various breeds, including dachshunds. Parker et al. (2009) identified an extra gene in short-legged breeds. The extra gene is a retrogene of the normal gene encoding fibroblast growth factor 4 (fgf4).

What is a retrogene? It's a derivative of the mature mRNA of a normal gene. Recall that most mammalian genes have introns and the primary transcript contains extra sequences at the two ends, plus exons that encode the amino acid sequence of a protein, plus intron sequences that separate the exons.

This primary transcript is processed to produce the mature messenger RNA (mRNA) that is subsequently translated by the translation machinery in the cytoplasm. During processing, the intron sequences are spliced out, a 5′ cap is added to the beginning of the RNA, and a string of "A" residues is added to the terminus (= poly A tail).


On rare occasions the mature mRNA can be accidentally copied by an enzyme called reverse transcriptase that converts RNA into single-stranded DNA. (The reverse of transcription, which copies DNA into RNA.) The single-stranded DNA molecule can be duplicated by DNA polymerase to make a double-stranded copy of the original mRNA molecule.

This piece of DNA may get integrated back into the genome by recombination. This is an extremely rare event but over the course of millions of years the genome accumulates many copies of such DNA sequences. In the vast majority of cases the DNA sequence is not expressed because it has been separated from its normal promoter. (Sequences that regulate transcription are usually not present in the primary transcript.) These DNA segments are called pseudogenes because they are not functional. They accumulate mutations at random and the sequence diverges from the sequence of the normal gene from which they were derived.

Sometimes the DNA copy of the mRNA happens to insert near a functional promoter and the DNA is transcribed. In this case the gene may be expressed and additional protein is made. Note that the new retrogene doesn't have introns so the primary transcript doesn't require splicing in order to join the coding regions (exons). The fgf4 retrogene inserted into the middle of a LINE transposable elements and the LINE promoter probably drives transcription of the retrogene.

The short-legged phenotype is probably due to inappropriate expression of the retrogene in the embryo in tissues that generate the long bones of the legs. The inappropriate expression of fibroblast growth factor 4 causes early calcification of cells in the growth plates—these are the cells that regulate extension of the growing bones. The result is short bones that are often curved.

Breeders selected for this anomaly and this is part of what contributed to the origin of dachshunds and other short-legged dogs.

There's a reason why dogs are such good species for discovering the functions of many genes. It's because of the huge variety of different breeds. Is there a reason why the species has more morphological variation than other species of animals? Probably, but we don't know the reason. Here's how Parker et al. begin their paper.

The domestic dog is arguably the most morphologically diverse species of mammal and theories abound regarding the source of its extreme variation (1). Two such theories rely on the structure and instability of the canine genome, either in an excess of rapidly mutating microsatellites (2) or an abundance of overactive SINEs (3), to create increased variability from which to select for new traits. Another theory suggests that domestication has allowed for the buildup of mildly deleterious mutations that, when combined, create the variation observed in the domestic dog (4).

We still have a lot to learn about evolution.

---

[Photo Credit: Dog Gone Good]

1. You can see why working with the cat genome wouldn't be as productive.

Parker, H.G., Vonholdt, B.M., Quignon, P., Margulies, E.H., Shao, S., Mosher, D.S., Spady, T.C., Elkahloun, A., Cargill, M., Jones, P.G., Maslen, C.L., Acland, G.M., Sutter, N.B., Kuroki, K., Bustamante, C.D., Wayne, R.K., and Ostrander, E.A. (2009) An Expressed Fgf4 Retrogene Is Associated with Breed-Defining Chondrodysplasia in Domestic Dogs. Science. 2009 Jul 16. [Epub ahead of print] [PubMed] [doi: 10.1126/science.1173275]

Pascal's Wager

 
Believe it or not, there are otherwise intelligent people out there who actually take Pascal's Wager seriously. Here's what happens ...

---

Are all Scientists on the Same Team?

 
I want to be like Janet D. Stemwedel when I grow up.

She has an amazing ability to think clearly and it's combined with an equally amazing ability to get her clear thoughts down on paper (or monitors). She is one of the reasons why I like all most some philosophers.

Her latest example is a discussion of Unscientific America, the book by Chris Mooney and Sheril Kirshenbaum that's causing so much turmoil in the blogosphere. I strongly urge you to read her posting from late Friday night called Unscientific America: Are scientists all on the same team?.

I posted a comment on Adventures in Ethics and Science in response to her posting. What I'm trying to do is explain why it is wrong for scientific organizations to take a position that excludes a large number of scientists. I'm including my comment here so that Sandwalk readers can have their say.

Excellent post, Janet. I agree with everything you say—except maybe for a few minor quibbles.

Chris and Sheril have missed the point about scientists having multiple goals and that's why many of their criticisms are misguided.

What can we do to find common goals that all scientists can share? I'd like to make one small suggestion. Scientific organizations such as AAAS, NAS, NIH, NSF etc. should remain strictly neutral with respect to religion. They should never take a stance on whether science and religion are compatible or incompatible. They should never promote the views of theistic scientists as being examples of excellent science BECAUSE these scientists are religious.

We all know that AAAS and NAS don't behave this way. They specifically use Francis Collins and Ken Miller as examples of good scientists who are also religious. They explicitly support the philosophical position that science is compatible with evangelical Christianity (Collins) and Roman Catholicism (Miller).

If all such organizations refrained from taking sides then ALL scientists, atheist and theist alike, could get behind their goals and support them. As soon as they start promoting the philosophical position of science/religion compatibility, they lose some of their potential supporters. The supporters they lose are the atheists who believe that science is not compatible with many of the beliefs of established religions.

The strict neutrality that I advocate should extend to the leadership of these organizations. Leaders of scientific organizations should not be prominently identified as supporters of religion or opponents of religion. This applies to the Director of NIH as well as other leadership positions.

Personally, I would extend the goal of strict neutrality to organizations like the National Center for Science Education (NCSE). If they maintain a big tent then all scientists, atheists and theists alike, can support their main goals. As soon as an organization like NCSE starts to promote the compatibility of science and religion by favoring theistic evolutionists over atheists—especially atheists who are opposed to compatibility—they create divisions. I don't think it is necessary for them to abandon and antagonize the vocal atheist scientists. NCSE disagrees, they have made a political decision to choose compatibility over neutrality because it advances their primary goal, which is separation of church and state.

These are complex issues. I don't get the impression that Chris and Sheril are aware of the complexity.

---

Web Site Story

 
I have a confession to make. I've always been a fan of West Side Story. I never saw the Broadway production but I saw the movie and even bought the soundtrack album back in 1961.

Some of the songs are true classics that are still being played on the radio today (Especially if you have satellite radio and listen to the 60s channel or the showtime channel. )

I bet every one of you can since a few bars of "Maria", "Tonight", "America", "I Feel Pretty", or "Somewhere" and probably most of you know a line or two from "Gee, Officer Krupke" and "Something's Coming".

Here's a very clever and funny, updated, version that was posted on A Blog Around the Clock.

See more funny videos and funny pictures at CollegeHumor.

---

Sometimes Violence Is Excusable

 
Here's Buzz Aldrin reacting to being called a coward and a liar. This is one of those times when I can't blame someone for throwing a punch.

---

[Hat Tip: Canadain Cynic]

Neutral pH

 

I'm working on the next edition of my textbook. From time to time I'm going to use you (readers) as guinea pigs to try out some new ideas. This is one of those times.

The concept of pH is difficult for students. It's easy for them to memorize the definition—the negative log of the hydrogen ion concentration—but that's not the same thing as understanding what it means.

Textbooks usually tell students that the equilibrium constant (K_eq) for the ionization of water is 1.8 × 10^-16. They can then calculate the ion product for water (K_w) at 25°C knowing the concentration of pure water (55.5 M). This value (1.0 × 10^-14) happens to be a convenient round number, giving rise to the standard pH scale from 1 to 14.

The square root of the ion product for water is the concentration of hydrogen ions ([H⁺]) and the concentration of hydroxide ions ([OH^-]). This concentration is 1.0 × 10^-7 or pH = 7.0, which corresponds to neutral pH at 25°C.

It occurs to me that students would have a better understanding of the concept if they were asked to do some calculations on their own rather than just reading the derivations in the textbooks. I propose to add the following problem. How many Sandwalk readers know the answer?

Neutral pH is the pH at which the concentrations of H⁺ and OH^- are equal in aqueous solvent. This pH is 7.0 for pure water at 25°C.

What is the neutral pH in your blood? What is the neutral pH in extremeophiles growing at 0°C or 100°C? (You may have to look up the values of some parameters in the Handbook of Chemistry & Physics).

Post your answers in the comments. You can post anonymously if you want but all the best biochemists will be signing their names.

Don't look at the comments until you come up with your own answer.

---

Monday's Molecule #129: Winner

 
The molecule is the Src protein tyrosine kinase from chicken (Gallus gallus). The scr gene is a proto-oncogene, meaning that is the normal version of an oncogene, or a cancer-causing gene. Mutant alleles of proto-oncogenes are responsible for many types of cancer.

A highly derived version of the normal src gene (v-src) is present in strains of the chicken Rous sarcoma virus discovered by Payton Rous in 1911. RSV causes cancer in chickens and it was the first cancer-causing virus to be identified.

It wasn't until the 1970's that the gene responsible for the cancer was identified and recognized as a derivative of a normal cellular gene involved in signal transduction and regulation of cell growth. Michael Bishop and Harold Varmus received the Nobel Prize for identifying the src gene as a proto-oncogene. They are this week's Nobel Laureates.

Many people got the right answer but the first one was Cody Cobb, soon to be a graduate student at Rutgers University in New Jersey. He will be joining me for lunch in a week or two.

---

Today's molecule is very famous so you aren't going to get any hints other than the fact it's from the species Gallus gallus

You need to name the molecule, identify its function, and explain why it is so famous. That will lead you to one or more Nobel Laureates whose Nobel Prize was directly related to this protein and, more importantly, its gene.

The first person to identify the molecule and the Nobel Laureate(s), wins a free lunch. Previous winners are ineligible for six weeks from the time they first won the prize.

There are seven ineligible candidates for this week's reward: Mike Fraser of the University of Toronto, Jason Oakley of the University of Toronto, Bill Chaney of the University of Nebraska, Ian Clarke of New England Biolabs Canada in Pickering ON, Canada. Dima Klenchin of the University of Wisconsin at Madison, Dara Gilbert of the University of Waterloo, and Anne Johnson of Ryerson University.

I have an extra free lunch for a deserving undergraduate so I'm going to continue to award an additional prize to the first undergraduate student who can accept it. Please indicate in your email message whether you are an undergraduate and whether you can make it for lunch.

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(s) and names the Nobel Laureate(s). Note that I'm not going to repeat Nobel Prizes so you might want to check the list of previous Sandwalk postings by clicking on the link in the theme box.

Correct responses will be posted tomorrow.

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

---

The figure is from Williams et al. (1997).

Williams, J.C., Weijland, A., Gonfloni, S., Thompson, A., Courtneidge, S.A., Superti-Furga, G., Wierenga, R.K. (1997) The 2.35 A crystal structure of the inactivated form of chicken Src: a dynamic molecule with multiple regulatory interactions. J. Mol. Biol. 274:757-75. [PubMed] [doi:10.1006/jmbi.1997.1426]

Chris Mooney and Sheril Kirshenbaum in Newsweek

 
Chris Mooney and Sheril Kirshenbaum have published an article in Newsweek [Defenders of the Faith: Scientists who blast religion are hurting their own cause].

The subtitle reveals that Mooney and Kirshenbaum just don't get it. I am a scientist who "blasts" religion. My "cause" is to demonstrate that religion is superstitious nonsense and should be abandoned. There are many people who share my opinion and they aren't all scientists. The fact that I am a scientist isn't really relevant.

The position that Mooney and Kirshenbaum adopt would be equivalent to saying that Christopher Hitchens should back off because he's hurting the "cause" of journalism, or that Rickey Gervais is hurting the "cause" of comedy, or Bill Gates is hurting the "cause" of making tons of money. They make the assumption that atheist scientists are only interested in promoting science (to the American public) and everything else is secondary.

This point has been explained to them hundreds of times. I don't know whether they are deliberately ignoring the facts order to frame the argument in their own terms or whether they are incapable of grasping the distinction we are tying to make.

There are times when Mooney and Kirshenbaum seem to be on the verge of understanding. The Newsweek article contains such an example. After the typical rant about how great Francis Collins is and how evil PZ Myers is, they go on to say ....

The public's willingness to reject science for religious reasons is certainly lamentable. But by arguing that science contradicts religion and makes it untenable, many atheists reinforce the very concerns that are keeping people from accepting science to begin with. Someone like Collins, by contrast, can convince those who think science conflicts with their beliefs that this needn't be the case.

This is the same old story we've heard before. Yes, it's true that someone like Francis Collins, who claims that science and religion are compatible, can be a great comfort to people who long to hear this. But that's not the point. The point is whether science and religion really are compatible. That's the question that certain atheists are asking and it won't be settled by pointing to Francis Collins. That's about as absurd as claiming that incompatibility is proven by pointing to Neil deGrasse Tyson or Jerry Coyne.

But wait. Here's where Mooney and Kirshenbaum offer us a glimmer of hope. They come very close to recognizing that the real question is whether science and religion are compatible and not just whether Collins thinks they are. They recognize that there's an "intellectual" question that might be important.

And Collins's approach isn't just good as a strategy to get the public to better appreciate science. The idea that science and religion can be compatible is strong on the intellectual merits as well. Granted, it depends how you define your terms: if your religion holds that Genesis must be read literally, then you are in direct conflict with scientific findings about the age of the Earth, the diversity of life on the planet, and so on. Yet if we consider religion more broadly—in its own considerable diversity—we find many sophisticated believers who've made a peace between their belief and the findings of modern science. It's not just Collins; consider the words of the Dalai Lama: "If science proves some belief of Buddhism wrong, then Buddhism will have to change."

Oh dear. Close but no cigar. They're still relying on the argument from authority—in this case the Dalai Lama—and their "evidence" still depends on the fallacy of The Doctrine of Joint Belief. And there's those mysterious "sophisticated believers" that we hear so much about but never actually encounter. Where are they hidden?

Still, there's a glimmer of hope. Keep trying, Chris and Sheril. One of these days you may see a frozen waterfall and everything will become clear.

UPDATE: James Hrynyshyn draws your attention to the same passage from the Newsweek article but he puts a different spin on it [Science v. Atheism: the Dalai Lama gambit]. Imagine that Francis Collins makes the same kind of statement that that Dalai Lama made. Collins would say, "If science proves some belief of Christianity wrong, then Christianity will have to change."

How many Christians want to hear that their religion might be wrong and might have to change?

---

[Hat Tip: RichardDawkins.net]

The Calling

 
I'm deeply suspicious of people who think they're doing God's will. But I'm positively frightened by people who believe they have been given responsible government positions (elected or appointed) because it is God's will.

Today I stumbled upon this passage from The Language of God by Francis Collins. He's discussing his appointment to head the Human Genome Project (pp. 118-119).

An intense national search ensued to find a new director. No one was more surprised than I to find the selection process converging on me. Being quite happy at the time leading a genome Center at the University of Michigan, and never having imagined myself as a federal employee, I initially indicated no interest. But the decision haunted me. There was only one Human Genome Project. This was going to be done only once in human history. If it succeeded, the consequences for medicine would be unprecedented. As a believer in God, was this one of those moments where I was somehow being called to take on a larger role in a project that would have profound consequences for our understanding of ourselves? Here was a chance to read the language of God, to determine the intimate details of how humans have come to be. Could I walk away? I have always been suspicious of those who claim to perceive God's will in moments such as this, but the awesome significance of this adventure, and the potential consequences for humankind's relationship with the Creator, could hardly be ignored.

Visiting my daughter in North Carolina in November 1992, I spent a long afternoon praying in a little chapel, seeking guidance about this decision. I did not "hear" God speak—in fact, I have never had that experience. But during those hours, ending in an evensong service that I had not expected, a peace settled over me. A few days later, I accepted the offer.

---

Rationalism vs Superstition: More than just Evolution vs Creationism

 
The Texas Board of Education is doing all of us a great favor by showing that the real fight isn't just evolution vs creationism or science vs religion. The real fight is religion vs everything. In other words, the problem isn't just creationists—it's people with a religious agenda.

We can see this now that the Texas Board of Education has turned its attention to modifying the social studies curriculum. They've appointed a panel of "experts" to recommend changes in the curriculum. There were three "experts" appointed by the conservative camp within the Board and three appointed by other side. The result is reported in The Wall Street Jounral [The Culture Wars' New Front: U.S. History Classes in Texas].

The three reviewers appointed by the moderate and liberal board members are all professors of history or education at Texas universities, including Mr. de la Teja, a former state historian. The reviewers appointed by conservatives include two who run conservative Christian organizations: David Barton, founder of WallBuilders, a group that promotes America's Christian heritage; and Rev. Marshall, who preaches that Watergate, the Vietnam War and Hurricane Katrina were God's judgments on the nation's sexual immorality. The third is Daniel Dreisbach, a professor of public affairs at American University.

The conservative reviewers say they believe that children must learn that America's founding principles are biblical. For instance, they say the separation of powers set forth in the Constitution stems from a scriptural understanding of man's fall and inherent sinfulness, or "radical depravity," which means he can be governed only by an intricate system of checks and balances.

The curriculum, they say, should clearly present Christianity as an overall force for good -- and a key reason for American exceptionalism, the notion that the country stands above and apart.

"America is a special place and we need to be sure we communicate that to our children," said Don McLeroy, a leading conservative on the board. "The foundational principles of our country are very biblical.... That needs to come out in the textbooks."

But the emphasis on Christianity as a driving force is disputed by some historians, who focus on the economic motivation of many colonists and the fractured views of religion among the Founding Fathers. "There appears to me too much politics in some of this," said Lybeth Hodges, a professor of history at Texas Woman's University and another of the curriculum reviewers.

Let's imagine for a moment that the conservative reviewers on the panel are theistic evolutionists. (This is a thought experiment, take it as a given.) How would my accommodationist friends deal with their recommendations? Is it okay to teach Christianity in history classes as long as it's kept out of science classes?

I wonder if the accommodationists see the potential problem with their position? They are happy to ally with theists as long as those theists accept science—or at least claim to accept science. But that's not all there is to the conflict between the religious and the non-religious.

What do we teach our children in the public schools? Do we teach them that morality comes from God or do we teach them that people can be moral without God? Or do we avoid the problem altogether and teach them nothing at all about the origins of morality?

In American schools do you teach that America is a Christian nation or do you teach that this is a myth that needs to be abandoned? Or is this another topic that has to be avoided in order to avoid conflicts with the Constitution?

---

Andrew Coyne on Conservative Values

We don't really have a (small "c") conservative party in Canada. The closest thing we have is the (large "C") Conservative Party but their policies include socialized medicine, government support of private industry, and a taxation scheme where the wealthy pay more.

I like Andrew Coyne even though we don't agree on anything. He's a smart guy and he knows what real (small "c") conservative values should look like. Running up huge deficits by increasing government spending is not part of the game. Neither is "corporate welfare."

Here's Andrew Coyne explaining why he disagrees with the current Canadian government. Apparently it has something to do with "principles," whatever they are.¹

---

1. No Canadian political party seems to have them.

[Hat Tip: Canadian Cynic]

Bastille Day

Today is the Fête Nationale in France known also as "le quatorze juillet" or Bastille Day.

This is the day in 1789 when French citizens stormed and captured the Bastille—a Royalist fortress in Paris. It marks the symbolic beginning of the French revolution although the real beginning is when the Third Estate transformed itself into the National Assembly on June 17, 1789 [Tennis Court Oath].

Ms. Sandwalk and I visited the site of the Bastille (Place de la Bastille) when we were in Paris last year. There's nothing left of the former castle but the site still resonates with meaning and history.

One of Ms Sandwalk's ancestors, William Playfair participated in the storming of the Bastille.

In honor of the French national day I invite you to sing the French national anthem, La Marseillaise. An English translation is provided so you can see that La Marseillaise is truly a revolutionary call to arms. (A much better translation can be found here.)

---

Check out Uncertain Principles for another version of La Marseillaise—this is the famous scene in Casablanca.

Monday's Molecule #129

 
Today's molecule is very famous so you aren't going to get any hints other than the fact it's from the species Gallus gallus

You need to name the molecule, identify its function, and explain why it is so famous. That will lead you to one or more Nobel Laureates whose Nobel Prize was directly related to this protein and, more importantly, its gene.

The first person to identify the molecule and the Nobel Laureate(s), wins a free lunch. Previous winners are ineligible for six weeks from the time they first won the prize.

There are seven ineligible candidates for this week's reward: Mike Fraser of the University of Toronto, Jason Oakley of the University of Toronto, Bill Chaney of the University of Nebraska, Ian Clarke of New England Biolabs Canada in Pickering ON, Canada. Dima Klenchin of the University of Wisconsin at Madison, Dara Gilbert of the University of Waterloo, and Anne Johnson of Ryerson University.

I have an extra free lunch for a deserving undergraduate so I'm going to continue to award an additional prize to the first undergraduate student who can accept it. Please indicate in your email message whether you are an undergraduate and whether you can make it for lunch.

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(s) and names the Nobel Laureate(s). Note that I'm not going to repeat Nobel Prizes so you might want to check the list of previous Sandwalk postings by clicking on the link in the theme box.

Correct responses will be posted tomorrow.

Comments will be blocked for 24 hours.

---

The figure is from Williams et al. (1997).
Williams, J.C., Weijland, A., Gonfloni, S., Thompson, A., Courtneidge, S.A., Superti-Furga, G., Wierenga, R.K. (1997) The 2.35 A crystal structure of the inactivated form of chicken Src: a dynamic molecule with multiple regulatory interactions. J. Mol. Biol. 274:757-75. [PubMed] [doi:10.1006/jmbi.1997.1426]

Timmy's Takes Manhattan

 
Tim Hortons is opening 13 stores in Manhattan and several more in Brooklyn. The first nine stores started serving coffee and donuts yesterday. Click here for a photo of New Yorkers lining up at the Penn Station store. The story even made the New York Times.

This is all part of a secret plot by Canadians to take over the best parts of the USA. (There are no plans to open stores in Texas.) Once we succeed we will impose universal health care¹ and ban Starbucks.

---

1. Also known as socialized medicine.