How Viagra Works

 
Mondays Molecule was sildenofil (5-[2-ethoxy-5- (4-methylpiperazin-1- ylsulfonyl) phenyl]-1- methyl-3-propyl-1,6-dihydro-7H-pyrazolo [4,3-d] pyrimidin-7-one) better known as its citrate salt, Viagra®.

Viagra® is most often used in the treatment of erectile disfunction. The way it works is to inhibit a specific enzyme called phosphodiesterase-5 located in the smooth muscle of the arteries that supply blood to the penis. In order to understand the significnace of this inhibition, we need a little background.

Nitric oxide (NO) is a chemical produced by special nerve cells called NANC nerve cells. (NANC stands for nonadrenergic-noncholinergic.) Under certain, rather special, conditions the brain sends a signal down the axon of a NANC nerve cell located in the penis. This causes NO to be released into the blood stream in the arteries of the penis.

One of the main roles of NO is to trigger the relaxation of the smooth muscle that lines the arteries. This leads to vasodilation and the lowering of blood pressure. In the penis this causes engorgement as the arteries expand and fill up with blood. The result is an erection that's stimulated by NO.

Nitric oxide acts locally. It diffuses into adjacent cells and binds to an enzyme called guanylyl cyclase. The binding of NO activates the enzyme, stimulating it to produce cyclic guanosine monophosphate or cGMP. The substrate for this reaction is guanosine triphosphate (GTP), a molecule that's similar to ATP except that the base is guanine instead of adenine.

ATP can be also be cyclized to form cAMP—a compound analogous to cGMP. cAMP is a common signal in many hormone-induced signal transduction pathways (and in creating a sense of smell). Like cAMP, cGMP is a signalling molecule. It activates specific enzymes that add phosphate to various proteins causing them to become more, or perhaps less, active. During an erection, the cGMP signal leads to changes in phosphorylation of muscle proteins causing the muscles to relax and the arteries to expand.

As you might expect, cGMP is not infinitely stable; otherwise a man might have an erection forever. cGMP is removed by the action of cGMP phosphodiesterase, which converts it to GMP. The turnover of cGMP in the penis is quite rapid leading to lack of signal unless NO is continually produced by the NANC nerve cells in order to replenish the supply of cGMP by reactivating guanylyl cyclase. This production of NO requires the attention of the brain, which has to keep focused on the task at hand.

The smooth muscle cells in the penis contain a special cGMP phosphodiesterase called phosphodiesterase-5 (PDE5). Sometimes the degradation of cGMP by PDE5 outpaces the production of cGMP by guanylyl cyclase. In such cases, the steady-state levels of cGMP aren't sufficient to signal muscle relaxation and no erection occurs. This is a common cause of erectile disfunction.

Viagra® works by inhibiting PDE5 thus blocking the breakdown of cGMP. This causes levels of cGMP to increase and an erection is prolonged. The structure of the PDE5 enzyme has been solved by Sung et al. (2003) in the presence of bound sildenafil (Viagra®) and two other inhibitors, tadalafil (Cialis®) and vardenafil (Levitra®). The structures are shown as stereo images in the figure below.

The upper image is the PDE5 proetin with overlapping molecules of sildenafil (red) and tadalfil (green) bound to the enzyme. The bottom images shown the structures of the three inhibitors. Viagra® binds to the site where cGMP would normally bind, thus blocking the degradation of cGMP. The structure of Viagra® is similar to cGMP and this exlains why it is such a potent inhibitor.

Sung B-J., Hwang, K.Y., Jeon, Y.H., Lee, J.I., Heo, Y.S., Kim, J.H., Moon, J., Yoon, J.M., Hyun, Y.L., Kim, E., Eum, S.J., Park, S.Y., Lee, J.O., Lee, T.G., Ro, S., and Cho, J.M. (2003) Structure of the catalytic domain of human phosphodiesterase 5 with bound drug molecules. Nature 425:98-102.

The Best Writing on Science Blogs 2006

 
Coturnix (A Blog Around the Clock) has put together an anthology of the best science writing on blogs for 2006. It's being published in a book called "the open laboratory." Read about The Great Unveiling and buy the book. Most of your friends are in it.

None of my contributions made the cut. Maybe next year. I'm still going to buy a copy when I'm in Chapel Hill next weekend.

Ethical Issues in Science

 
One of the things I have to do this week is deal with the teaching of so-called "ethics" in genetics and biochemistry courses. Let me give you two examples in order to focus the debate: genetically modified foods, and a proper diet.

It's almost a requirement these days that introductory genetics courses include a section on genetically modified crops. This invariably leads to tutorials, or labs, or essays, about whether GM-foods are a good thing or not. These discussions are usually lots of fun and the students enjoy this part of the course. Professors are convinced they are teaching ethics and that it's a good thing to show students that ethics is an important part of science.

In introductory biochemistry courses we often have a section on fuel metabolism. That's the part of biochemistry that deals specifically with how your food is converted to energy. It's human biochemistry. In that section of the course the Professor often raises the question of proper diet. Is it okay to eat meat? Are trans fatty acids bad for you? Should you be eating carbohydrates? Our experience is that Professors who teach this section often have very strong opinions and their personal ethical stance is portrayed as scientific fact.

These are two different cases. In the first one, the question is whether the value of debating controversial "ethical" issues outweighs the disadvantages. The biggest downside, in my opinion, is the emphasis on technology as opposed to pure basic science. By giving prominence to "ethical" issues we are emphasizing the consequences of genetic knowledge as it relates to the human condition.

I prefer to spend my time trying to convince students that knowledge for its own sake is valuable. It's hard to do that if the fun part of the course has to do with the application of genetic technology in the creation of genetically modified foods.

The second case involves a different kind of ethics. Here, the students aren't debating whether you should eat trans fatty acids or not. They are being given an ethical perspective disguised as a scientific fact. I don't think this is a good idea. At the very least, the issue should be presented as controversial and students should be encouraged to read the medical literature; which, by the way, has very little to do with the biochemistry being taught in class.

Should students be discussing the benefits of the Atkins diet? Perhaps, but it should be a discussion and not a lecture, right? And does a focus on human eating behavior detract from the importance of basic scientific knowledge? I think it does.

Part of the problem arises from a desire to please the students. How often do we hear the complaint that students aren't interested in biochemistry and genetics? The students are bored by science so we have to add sections on genetically modified foods and genetic screening to our introductory genetics courses. Isn't this strange? Rather than concentrate on making the basic science as interesting and exciting as possible, we cater to the students by giving them the topics they think are interesting. That's no way to educate.

There's another problem; what is ethics? Sometimes it's hard to see the difference between simple controversy and ethics. Sometimes it's hard to define exactly what "ethics" is all about in spite of the fact that "bioethics" is one of the biggest growth industries in science. Here's where a philosopher or two could weigh in.

Plastic Duckies

 
On January 29, 1992 a 40-foot container fell off a ship in the middle of the Pacific Ocean. Inside the container were 29,000 "Floatees," small bathtub toys. There were blue turtles, yellow ducks, red beavers, and green frogs. Over the next few years, these toys washed up on shores all around the Pacific, especially in Indonesia, Australia, and South America [Friendly Floatees].

The story of these Floatees has been told many times. For years beachcombers around the world have been talking about Beachcombing Science from Bath Toys.

Thousands of the Floatees drifted north where they passed through the Bering Straight and became locked in the pack ice north of the Arctic Circle. The prediction was that they would emerge into the Atlantic in 2003 and, sure enough, Floatees started to turn up in New England and Great Britain. More are expected this year [Drake's other armada].

There's a picture of a plastic duckie on the cover of this month's Harpers magazine. The feature story is MOBY-DUCK: Or, the Synthetic Wilderness of Childhood by Donovan Holn. It's a wonderful read. Donaovan Holn has weaved together the story of the Floatees and his personal voyage of discovery. As you follow along you will learn about ocean currents, flotsam and jetsam, beachcombing, childhood, and so much more.

Astrobiology: A Null Set

 
Phil Plait of Bad Astronomy recently lost out to PZ Mierz of Pharyngula in the contest for best blog. His penalty for not getting enough astronomy enthusiasts to cast ballots is to write something about biology.

So naturally he chooses Astrobiology as his example— a discipline without a single living example. Typical astronomer, taking the easy way out.

As I tell my students, biology is much harder than physics and astronomy. Any biologist can handle physics with their eyes closed but physics students (and Professors) are afraid of biology. It's way too messy for them.

The Logic of Irreducible Complexity

 
Ross Thomas (HALFaCANUCK) uses predicate calculus to analyze whether the following argument,

the irreducibly complex nature of the eye proves God's existence

is logically correct. [Irreducible illogicality] The answer will surprise you.

P.S. Don't tell the IDiots about this one!

Alanis Morissette Doesn't Get Irony

 
Guy Kawasaki interviews Jon Winokur [Ten Questions with Jon Winokur: How to Heighten Your Sense of the Absurd]. In response to a question about what he's working on now (Q12) Winokur say he's writing a book called The Big Curmudgeon. Winokur then goes ont to say,

It drives me crazy when people say “ironic” when they mean “coincidental.” The classic example is Morissettian Irony, which I define in the book as “irony based on a misapprehension of irony, i.e., no irony at all.” It’s named for the pop singer Alanis Morissette, whose hit single, “Ironic” mislabels coincidence and inconvenience as irony.

In the song, situations purporting to be ironic are merely sad, random, or annoying (“It's a traffic jam when you're already late/It's a no-smoking sign on your cigarette break”). In other words, “Ironic” is an un-ironic song about irony. Which, of course, is ironic in itself. But wait, there’s more, a “bonus irony” if you will: “Ironic” has been cited as an example of how Americans don’t get irony, despite the fact that Alanis Morissette is Canadian!

I hate it when people don't get irony ... or sarcasm.

[To see the video, go to Alanis Morissette, click on "music" then on "ironic" at the bottom, third from the left.]

[Hat Tip: Jim Lippard]

[Photo Credit: Agência Brasil disponibiliza, gratuitamente, imagens e fotos. Para cumprir a legislação em vigor, solicitamos aos nossos usuários a gentileza de registrar os créditos como no exemplo: nome do fotógrafo—via Wikipedia.]

Basic Concepts: The Central Dogma of Molecular Biology

The demise of the Central Dogma of Molecular Biology is becoming an annual event. Most recently, it was killed by non-coding RNA (ncRNA) (Mattick, 2003; 2004). In previous years the suspects included alternative splicing, reverse transcriptase, introns, junk DNA, epigenetics, RNA viruses, trans-splicing, transposons, prions, epigenetics, and gene rearrangements. (I’m sure I’ve forgotten some.)

What’s going on? The Central Dogma sounds like the backbone of an entire discipline. If it’s really a “dogma” how come it gets refuted on a regular basis? If it’s really so “central” to the field of molecular biology then why hasn’t the field collapsed?

In order to answer these questions we need to understand what the Central Dogma actually means. It was first proposed by Francis Crick in a talk given in 1957 and published in1958 (Crick, 1958). In the original paper he described all possible directions of information flow between DNA, RNA, and protein. Crick concluded that once information was transferred from nucleic acid (DNA or RNA) to protein it could not flow back to nucleic acids. In other words, the final step in the flow of information from nucleic acids to proteins is irreversible.

Fig. 1. Information flow and the sequence hypothesis. These diagrams of potential information flow were used by Crick (1958) to illustrate all possible transfers of information (left) and those that are permitted (right). The sequence hypothesis refers to the idea that information encoded in the sequence of nucleotides specifies the sequence of amino acids in the protein.

Crick restated the Central Dogma of Molecular Biology in a famous paper published in 1970 at a time when the premature slaying of the Central Dogma by reverse transcriptase was being announced (Crick, 1970). According to Crick, the correct, concise version of the Central Dogma is ...

... once (sequential) information has passed into protein it cannot get out again (F.H.C. Crick, 1958)

The central dogma of molecular biology deals with the detailed residue-by-residue transfer of sequential information. It states that such information cannot be transferred from protein to either protein or nucleic acid. (F.H.C. Crick, 1970)

Announcing the (Premature) Death of the Central Dogma
The central dogma of biology holds that genetic information normally flows from DNA to RNA to protein. As a consequence it has been generally assumed that genes generally code for proteins, and that proteins fulfil not only most structural and catalytic but also most regulatory functions, in all cells, from microbes to mammals. However, the latter may not be the case in complex organisms. A number of startling observations about the extent of non-protein coding RNA (ncRNA) transcription in the higher eukaryotes and the range of genetic and epigenetic phenomena that are RNA-directed suggests that the traditional view of genetic regulatory systems in animals and plants may be incorrect.

Mattick, J.S. (2003) Challenging the dogma: the hidden layer of non-protein-coding RNAs in complex organisms. BioEssays 25:930-939.

---

The central dogma, DNA makes RNA makes protein, has long been a staple of biology textbooks.... Technologies based on textbook biology will continue to generate opportunities in bioinformatics. However, more exciting prospects may come from new discoveries that extend or even violate the central dogma. Consider developmental biology. The central dogma says nothing about the differences between the cells in a human body, as each one has the same DNA. However, recent findings have begun to shed light on how these differences arise and are maintained, and the biochemical rules that govern these differences are only being worked out now. The emerging understanding of developmental inheritance follows a series of fundamental discoveries that have led to a realization that there is more to life than the central dogma.

Henikoff, S. (2002) Beyond the central dogma. Bioinformatics 18:223-225.

---

It will take years, perhaps decades, to construct a detailed theory that explains how DNA, RNA and the epigenetic machinery all fit into an interlocking, self- regulating system. But there is no longer any doubt that a new theory is needed to replace the central dogma that has been the foundation of molecular genetics and biotechnology since the 1950s.

The central dogma, as usually stated, is quite simple: DNA makes RNA, RNA makes protein, and proteins do almost all of the work of biology.

Gibbs. W.W. (2003) The unseen genome: gems among the junk. Sci. Am. 289:26-33.

Unfortunately, there’s a second version of the Central Dogma that’s very popular even though it’s historically incorrect. This version is the simplistic DNA → RNA → protein pathway that was published by Jim Watson in the first edition of The Molecular Biology of the Gene (Watson, 1965). Watson’s version differs from Crick’s because Watson describes the two-step (DNA → RNA and RNA → protein) pathway as the Central Dogma. It has long been known that these conflicting versions have caused confusion among students and scientists (Darden and Tabery, 2005; Thieffry, 1998). I argue that as teachers we should teach the correct version, or, at the very least, acknowledge that there are conflicting versions of the Central Dogma of Molecular Biology.

The pathway version of the Central Dogma is the one that continues to get all the attention. It’s the version that is copied by almost all textbooks of biochemistry and molecular biology. For example, the 2004 edition of the Voet & Voet biochemistry textbook says,

In 1958, Crick neatly encapsulated the broad outlines of this process in a flow scheme he called the central dogma of molecular biology: DNA directs its own replication and its transcription to yield RNA, which, in turn, directs its translation to form proteins. (Voet and Voet, 2004)

If the Watson pathway version of the Central Dogma really was the one true version then it would have been discarded or modified long ago. In his original description, Watson drew single arrows from DNA to RNA and from RNA to protein and stated ....

The arrow encircling DNA signifies that it is the template for its self-replication; the arrow between DNA and RNA indicates that all cellular RNA molecules are made on DNA templates. Most importantly, both these latter arrows are unidirectional, that is, RNA sequences are never copied on protein templates; likewise, RNA never acts as a template for DNA.

Fig. 2. Watson’s version of the Central Dogma. This figure is taken from the first edition of The Molecular Biology of the Gene (p. 298).

Watson's statement is clearly untrue, as the discovery of reverse transcriptase demonstrated only a few years after his book was published. Furthermore, there are now dozens of examples of information flow pathways that are more complex than the simple scheme shown in Watson’s 1965 book. (Not to mention the fact that many information flow pathways terminate with functional RNA’s and never produce protein.)

Watson’s version of the Central Dogma is the one scientists most often refer to when they claim that the Central Dogma is dead. The reason it refuses to die is because it is not the correct Central Dogma. The correct version has not been refuted.

Crick was well aware of the difference between his (correct) version and the Watson version. In his original 1958 paper, Crick referred to the standard information flow pathway as the sequence hypothesis. In his 1970 paper he listed several common misunderstandings of the Central Dogma including ....

It is not the same, as is commonly assumed, as the sequence hypothesis, which was clearly distinguished from it in the same article (Crick, 1958). In particular, the sequence hypothesis was a positive statement, saying that the (overall) transfer nucleic acid → protein did exist, whereas the central dogma was a negative statement saying that transfers from protein did not exist.

The Sequence Hypothesis and the Central Dogma in 1957
My own thinking (and that of many of my colleagues) is based on two general principles, which I shall call the Sequence Hypothesis and the Central Dogma. The direct evidence for both of them is negligible, but I have found them to be of great help in getting to grips with these very complex problems. I present them here in the hope that others can make similar use of them. Their speculative nature is emphasized by their names. It is an instructive exercise to attempt to build a useful theory without using them. One generally ends in the wilderness.

The Sequence Hypothesis. This has already been referred to a number of times. In its simplest form it assumes that the specificity of a piece of nucleic acid is expressed solely by the sequence of its bases, and that this sequence is a (simple) code for the amino acid sequence of a particular protein.

This hypothesis appears to be rather widely held. Its virtue is that it unites several remarkable pairs of generalizations: the central biochemical importance of proteins and the dominating role of genes, and in particular of their nucleic acid; the linearity of protein molecules (considered covalently) and the genetic linearity within the functional gene, as shown by the work of Benzer and Pontecorvo; the simplicity of the composition of protein molecules and the simplicity of nucleic acids. Work is actively proceeding in several laboratories, including our own, in an attempt to provide more direct evidence for this hypothesis.

The Central Dogma. This states that once “information” has passed into protein it cannot get out again. In more detail, the transfer of information from nucleic acid to nucleic acid, or from nucleic acid to protein may be possible, but transfer from protein to protein, or from protein to nucleic acid is impossible. Information means here the precise determination of sequence, either of bases in the nucleic acid or of amino acid residues in the protein.

Crick, F.H.C. (1958) On protein synthesis. Symp. Soc. Exp. Biol. XII:138-163 quoted in Judson, H.F. The Eight Day of Creation, Expanded Edition (1979, 1996) p. 332.

So, how do we explain the current state of the Central Dogma? The Watson version is the one presented in almost every textbook, even though it is not the correct version according to Francis Crick. The Watson version has become the favorite whipping boy of any scientist who lays claim to a revolutionary discovery, even though a tiny bit of research would uncover the real meaning of the Central Dogma of Molecular Biology. The Watson version has been repeatedly refuted or shown to be incomplete, and yet it continues to be promoted as the true Central Dogma. This is very strange.

The Crick version is correct—it has never been seriously challenged—but few textbooks refer to it. One exception is Lewin’s GENES VIII (Lewin, 2004) (and earlier editions). Lewin defines the Central Dogma of Molecular Biology as,

The central dogma states that information in nucleic acid can be perpetuated or transferred but the transfer of information into protein is irreversible. (B. Lewin, 2004)

I recommend that all biochemistry and molecular biology teachers adopt this definition—or something very similar—and teach it in their classrooms.

Crick, F.H.C. (1958) On protein synthesis. Symp. Soc. Exp. Biol. XII:138-163. [PDF]

Crick, F. (1970) Central Dogma of Molecular Biology. Nature 227, 561-563. [PDF file]

Darden, L. and Tabery, J. (2005) Molecular Biology

Lewin, B. (2004) GENES VIII Pearson/Prentice Hall

Mattick, J.S. (2003) Challenging the dogma: the hidden layer of non-protein-coding RNAs in complex organisms. BioEssays 25:930-939

Mattick, J.S. (2004) The hidden genetic program of complex organisms. Sci. Am. 291:60-67.

Thieffry, D. (1998) Forty years under the central dogma. Trends Biochem. 23:312-316.

Watson, J.D. (1965) The Molecular Biology of the Gene. W.A. Benjamin. Inc. New York

Chapel Hill, North Carolina

I'm going to Chapel Hill next weekend. It's one of my favorite places in the world. My daughter lives there. (Hi Jane, are you ready?)

I'm going to meet some bloggers.

Monday's Molecule #9

 
Name this molecule. You must be specific. We need the exact chemical name and the common name. The common name will be much more familiar to you. We'll discuss how this molecule works after you've been given a chance to identify it.

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

Even at a conference, you've got to eat!

 
Even at a conference, you've got to eat! I'm going to Mama Dip's for Bar-B-Que on Saturday night. Are you going too?

Chicken with Ribs
pork ribs and choice of fried or bar-b-que chicken
Chopped Bar-B-Que Pork with Chicken
choice of fried or bar-b-que chicken
Brunswick Stew & Chopped Bar-B-Que
served with coleslaw and cornbread only
Bar-B-Que Pork Ribs & Chopped Bar-B-Que Pork
for the true connoisseur
Chicken & Dumplings
broiled chicken seasoned and cooked with rolled dumplings
Chittlins
really "down home" served plain or pan fried
Chicken & Gravy
our 1/4 fried chicken smothered in gravy, white or dark meat
Salmon Biscuit
fried salmon patty sandwiched between a sliced buttermilk biscuit
Country Ham Biscuit
country ham sandwiched between a sliced buttermilk biscuit
Sausage Biscuit
pork sausage sandwiched between a sliced buttermilk biscuit
Chicken Tender Biscuit
chicken tenders smothered in gravy sandwiched between a sliced buttermilk biscuit
Sweet Potato Biscuit
Mama Dip's sweet potato biscuits served hot with butter

Safer than LSD and 'Shrooms

 
Would you take this drug if it made you dream you were climbing in the Himalayas with a duck, an ape, and a turtle? Kevin Beck would.

The duck wasn't a very good climber but it was turtles all the way up.

There's Some Kinda Test Going ON

 
The BBC reports that South Africa close in on victory. Here's an excerpt from the article,

Nazir was dropped by Pollock before the break off the luckless Ntini and could have been run out twice before thrashing the seamer over mid-wicket for six and seeing his stumps re-arranged attempting a repeat.

Naved, who survived a strong caught behind appeal off Pollock in the first over after tea, and Kaneria took over to launch a succession of meaty blows.

Three fours came in one over from Ntini and a startled Pollock was thrashed over long-off and mid-wicket for huge maximums.

Harris saw off Kaneria to bring the carnage to an end but the momentum had shifted back towards Pakistan.

Hmmm ... it looks like English but .....

Does anyone want to explain to this ignorant Canadian what's happening?

A Professor's Worst Nighmare

 
Has this ever happened to you? Read what happens when a Professor doesn't look in the mirror after putting on his pants [A classic professorial moment].

Time-shifting "Studio 60 on the Sunset Strip"

 
Freakonomics reports that my favorite TV show, Studio 60 on the Sunset Strip, is the show that people are most likely to record and watch at some other time [“Studio 60″: Tops in Time-Shifting]. I thought this might reflect the sophistication of the Studio 60 audience but then I read the rest of the top ten time-shifted shows .....

Massacre in Canada

 
The results of the latest grant competition in Canada are leaking out and the news is bad. Canadian health science research is being gutted.

The main funds for health science research come from the Canadian Institutes of Health Research (CIHR). This is the agency that funds basic science in biochemistry, molecular biology, immunology, human genetics etc. CIHR grants are the backbone of research in my department (Biochemistry) and many others.

The word from CIHR is that only 15% of the September applicants will be funded. Many of my colleagues have already received notice that they are below the cutoff. Their grants will be terminated.

These colleagues are not incompetent scientists. Many of them publish 3-5 papers a year in high quality journals. In most cases they have had continuous funding since they were first hired 10-20 years ago. Their groups consist of research assistants (lab technicians), several post-docs, and several graduate students. The lab techs and the post-docs will be terminated and the graduate students may not be able to finish their degrees.

This is a disaster. You cannot sustain high quality research if your chances of getting a grant are only 15%. What's happening is that excellent scientists are being kicked out of the system due to lack of funds at CIHR. This has got to change. The Conservative Government of Stephen Harper is ruining careers.

Already there's talk of a moratorium on hiring new faculty members. Why should we bring in new scientists if their chances of success are so small? (The funding rate for new grants is even lower than 15%.)

Stay tuned.

Birth-and-Death Evolution in Mammalian Gene Families

Once we recognize the accidental nature of evolution as described in birth-and-death evolution of gene families [The Evolution of Gene Families] we are better prepared to appreciate the significance of other studies.

In an earlier posting [Mammalian Gene Families: Humans and Chimps Differ by 6%] I described the results of Demuth et al. (2006) who looked at global expansion and contraction of gene families. They published this diagram to show the extent of gene loss and gain in mammalian lineages.

Figure 1. Distribution of gene gain and loss among mammalian lineages.

Creative Commons Attribution License

The Creationists made a big deal about this when the paper first came out but we can now see that the expansion and contraction of gene families is just part of the normal, ongoing, process of birth-and-death evolution.

Can Anyone Answer This Question?

 
Check out the new look of Uncommon Descent, the blog by Dembski, O'Leary, and friends. It almost looks as though someone intelligent designed it.

Isn't it interesting that the best they can come up with is a bacterial flagellum—a structure whose evolution is getting to be fairly well understood?

While you're there, read Every day biology is looking more and more designed and see if you can answer the question posed by the author,

I receive Nature E-Alerts in a number of biological research fields. Almost every time I read the abstracts and even the titles, or spend more time delving into the detail, I hear “Intelligent Design” silently screamed from the pages. Am I deluded ...?

Update: Joshua Rosenau has an answer at [Simple answers to stupid questions (now with bonus answer to bonus question!)].

The Evolution of Gene Families

The genes for olfactory receptors are part of a gene family. A gene family, by definition, means that there's two or more related genes in a genome. In the case of olfactory receptor genes there are hundreds of different genes spread out over many chromosomes. All the copies are closely related (homologous). They clearly descend from a common ancestor following a gene duplication event.

The evolution of gene families has been studied for over 50 years. We now recognize three different modes of evolution. The two simplest modes are shown below.

Imagine a gene duplication event occurring in a common ancestor at the left-hand side of these trees. Two genes, A and B, are now present in the genome of every species that descends from this common ancestor. In divergent evolution, each of the genes evolves independently after the duplication. Thus, we have two separate phylogenies: one for the A genes and one for the B genes. The two phylogenies will be identical. This is the most common mode of evolution for gene families, especially if the A gene and the B gene are separated in the genome (i.e., on different chromosomes). The classic example is evolution of the α- and β-globin genes in vertebrates.

In concerted evolution, the trees looks like the one on the right. If we assume that the gene duplication event occurred in the last common ancestor of fish, chickens, mice, and humans, then the pattern we see looks very strange. Instead of showing two independent phylogenies, the A and B genes in each species are much more closely related to each other than to family members in any other species. The prototypical example is the evolution of ribosomal RNA genes in all species.

This form of evolution is termed concerted evolution because the pair of genes (A and B) evolved in a concerted manner. They talk to each other. When a mutation occurs in one gene it is transferred to the other so that both genes change in the same direction. The only differences between family members within a species are those that have only become fixed in the very recent past.

The most important mechanism of concerted evolution is gene conversion. This is a form of recombination where the sequence of one gene "converts" the other. It explains how the two genes can communicate. Gene conversion can take place between any two homologous genes in the genome but it is much more common between two homologous genes that are adjacent to each other, especially if they are transcribed in the same direction as a result of a tandem duplication. Gene conversion has been well studied. It is known to produce the results shown in the figure.

There's another way to explain the result in the right-hand tree without invoking concerted evolution. It's possible that our initial assumption is wrong. Perhaps the common ancestor had only a single gene and gene duplications occurred independently within each lineage. This would give a result similar to the tree shown. While this is possible, it seems very unlikely that for a single pair of genes the same duplication would occur in every lineage. With larger genes families such multiple duplication events are more probable.

The third mode of gene family evolution is a combination of the patterns seen in divergent evolution and in concerted evolution. If duplications of family members occur frequently then this gives rise to the birth of new genes. Newborn genes will closely resemble one another, as in concerted evolution. The number of family members does not keep expanding because some of the genes become inactivated—they become pseudogenes and they die. The resulting pattern of evolution will look like a mixture of divergent and concerted evolution. The mode is called "birth-and-death."

The figure below is from a review by Nei and Rooney (2005). Masatoshi Nei is one of the discoverers of birth-and-death evolution (Nei and Hughes, 1992).

Note that in birth-and-death evolution some genes survive in a lineage and some genes are lost. The birth and death of genes can be random or it can be under selection. The point is that not all members of the gene family in the ancestor will show up in all species descending from the common ancestor, and that sometimes several members of the gene family will be much more closely related than you would expect from divergent evolution.

Niimura and Nei (2006) studied the evolution of olfactory receptor genes. In order to study the evolution of gene families you have to be sure you have included every copy of the gene in your study. If you're going to test birth-and-death hypotheses, you also have to include all the pseudognes.

Niimura and Nei (2006) were able to do this for the mouse and human olfactory receptor genes because the complete genomes have been published. By examining the sequences of all genes and pseudogenes, they were able to determine that the most recent common ancestor (MCRA) of mice and humans had 754 functional genes (see figure below). Of these ancestral genes, 691 are still functional in the mouse genome but only 326 remain functional in the human genome.

This study can now be extended because there are complete genome sequences of chickens, frogs, and fish. In addition, there is enough sequence information from lampreys to estimate the number of olfactory receptor genes in that species.

The result is shown above in (b). The ancestor of jawed and jawless fish had two olfactory receptor genes: one type 1 gene and one type 2 gene. Each of these genes gave rise to subfamilies in fish so that the MCRA between fish and tetrapods had six type 1 genes and three type 2 genes. Various members of these subfamilies expanded or contracted in number in the lineages leading to modern fish, amphibians, birds, and mammals. This is birth-and-death evolution.

The patterns produced by birth-and-death evolution look much more like random fluctuations than something produced by sustained directional selection. Niimura and Nei (2006) caution against adaptationist explanations of the differing numbers of genes in various species of mammals. For example, it is widely assumed that the reason mice have more functional olfactory receptor genes than humans is because mice have a better sense of smell. But Niimura and Nei (2006) point out that dogs are supposed to have an excellent sense of smell even though they have fewer OR genes than rodents. The number of genes could be due to chance and not selection. (Or, most likely, a combination of accident and selection.)

Nei, M. and Hughes, A.L. (1992) Balanced polymorphism and evolution by the birth-and-death process in the MHC loci. In 11th Histocompatibility Workshop and Conference, ed. K. Tsuji, M. Aizawa, and T. Sasazuki, pp. 27-28. Oxford, UK: Oxford Univ. Press

Nei, M. and Rooney, A. P. (2005) Concerted and Birth-and-Death Evolution in Multigene Families. Ann. Rev. Genet. 39: 121-152.

Niimura, Y. and Nei, M. (2006) Evolutionary dynamics of olfactory and other chemosensory receptor genes in vertebrates. J. Hum. Genet. 51: 505-517.

Evolution and Religion According to John West

 
John West, one of the leading IDiots at the Discovery Institute, continues his defense of religion (his version) with A Further Response to Larry Arnhart, pt. 4: Darwinism, Religion, and Intelligent Design. He says,

In the section of my book on religion, I make clear that “evolution” can be compatible with theism in general and Biblical theism in particular—depending on how one defines the term “evolution.” If all one means by “evolution” is “change over time,” or “microevolution” through natural selection, or even biological “common descent,” then evolution would seem perfectly compatible with most forms of theism. Only if one insists that evolution is an undirected Darwinian process of chance and necessity, with no particular end in view, does there seem to be a serious problem with traditional theism.

Personally, I wouldn't use the term "Darwinism." I would say. "According to science, evolution is an undirected process with no particular end in view." In a rare example of intelligent insight, West has recognized a truth that many evolutionists and appeasers overlook. The scientific version of evolution is not compatible with theism.

Basic Terms and Concepts

 
Coturnix over at Blog Around the Clock has proposed an explanation of Basic Terms and Concepts. This seems to be an idea hatched by the ScienceBlogs group, but I'm going to assume that anyone can play. John Wilkins has started it off with his expanation of CLADE.

The post below is my definition of Evolution and I'll follow up with The Central Dogma of Molecular Biology tomorrow Monday.

What Is Evolution?

Most non-scientists seem to be quite confused about precise definitions of biological evolution. Part of the confusion is because the word "evolution" has many different meanings, depending on the context. When we talk about biology we are thinking about biological evolution and that's the term I want to define here. What do biologists mean when they refer to biological evolution?

One of the most respected evolutionary biologists has recently defined biological evolution as follows:

Biological (or organic) evolution is change in the properties of populations of organisms or groups of such populations, over the course of generations. The development, or ontogeny, of an individual organism is not considered evolution: individual organisms do not evolve. The changes in populations that are considered evolutionary are those that are ‘heritable' via the genetic material from one generation to the next. Biological evolution may be slight or substantial; it embraces everything from slight changes in the proportions of different forms of a gene within a population, such as the alleles that determine the different human blood types, to the alterations that led from the earliest organisms to dinosaurs, bees, snapdragons, and humans.

Douglas J. Futuyma (1998) Evolutionary Biology 3rd ed., Sinauer Associates Inc. Sunderland MA p.4

Note that biological evolution refers to populations and not to individuals. In other words, populations evolve but individuals do not. This is a very important point. It distinguishes biological evolution from other forms of evolution in science (e.g., stellar evolution). Another important point is that the changes must be genetic, or heritable—they must be passed on to the next generation. Evolution is the process by which this occurs and it is spread out over many generations. Thus, the short minimal definition of biological evolution is,

Evolution is a process that results in heritable changes in a population spread over many generations.

This is a good working scientific definition of evolution; one that can be used to distinguish between evolution and similar changes that are not evolution. Another common short definition of evolution can be found in many textbooks:

In fact, evolution can be precisely defined as any change in the frequency of alleles within a gene pool from one generation to the next.

Helena Curtis and N. Sue Barnes, Biology, 5th ed. 1989 Worth Publishers, p.974

One can quibble about the accuracy of such a definition, but it also conveys the essence of what evolution really is. When biologists say they have observed evolution, they mean that they have detected a change in the frequency of genetic variants (alleles) in a population. (Often the genetic change is inferred from phenotypic changes.) When biologists say that humans and chimps have evolved from a common ancestor, they mean there have been successive heritable changes in the two separated populations since they became isolated.

Unfortunately, outside of the scientific community, the common definitions of evolution are quite different. For example, in the Oxford Concise Science Dictionary we find the following definition:

evolution: The gradual process by which the present diversity of plant and animal life arose from the earliest and most primitive organisms, which is believed to have been continuing for the past 3000 million years

This is inexcusable for a dictionary that's supposed to be a dictionary of science. Not only does this definition exclude prokaryotes, protozoa, and fungi, but it specifically includes a term "gradual process" that should not be part of the definition. More importantly the definition seems to refer more to the history of evolution than to evolution itself. Using this definition it is possible to debate whether evolution is still occurring, but the definition provides no easy way of distinguishing evolution from other processes. For example, is the increase in height among Europeans over the past several hundred years an example of evolution? Are the color changes in peppered moth populations examples of evolution? The definition of evolution in the Oxford Concise Science Dictionary is not a proper scientific definition of evolution.

Standard dictionaries are even worse.

evolution: ...the doctrine according to which higher forms of life have gradually arisen out of lower.. (Chambers)

evolution: ...the development of a species, organism, or organ from its original or primitive state to its present or specialized state; phylogeny or ontogeny (Webster's)

These definitions are simply wrong. The problem is that it's common for non-scientists to enter into a discussion about evolution with such a definition in mind. This often leads to fruitless debate since the experts are thinking about evolution from a different perspective. When someone claims they don't believe in evolution they cannot be referring to an acceptable scientific definition of biological evolution because that would be denying something that is easy to prove. It would be like saying they don't believe in gravity!

Anti-evolutionists often claim scientists are being dishonest when they talk about evolution. The anti-evolutionists believe that evolution is being misrepresented to the public. The real problem is that the public in general, and anti-evolutionists in particular, do not understand what evolution is all about. Their definition of evolution is very different from the common scientific definition and, as a consequence, they are unable to understand what evolutionary biology really means. Scientist are not trying to confuse the general public by using a rigorous definition of evolution. Quite the contrary, saying that evolution is simply "a process that results in heritable changes in a population spread over many generations" is a way of simplifying discussions about evolution.

Note that I have described the minimal scientific definition of biological evolution. Nobody believes that this is all there is to evolution. There are other processes, such as speciation for example, that are clearly important parts of the process of evolution. [Macroevolution]

Objections to the Minimal Definition

Some people, including some scientists, are uncomfortable with this minimal definition because they think it excludes some important parts of evolutionary biology. I'll try and discuss the various objections in a short while but first let me explain why we need a strict minimal definition in the first place.

I've already alluded to one of the classic questions that a proper definition can answer—the increased height of Europeans over the past five centuries. Armed with a good definition of biological evolution we can focus on one of the key requirements; namely, heritable change. It turns out that the increase in height is due to a better diet and not to genetic changes. Therefore, this is not evolution according to the scientific definition.

We can also ask whether the development of antibiotic resistance in bacteria is a valid example of biological evolution. In this case the answer is "yes" because a new antibiotic resistance allele has arisen by mutation and subsequently became fixed in the population. Anyone who wants to offer an alternative minimal definition of evolution will have to make sure that it will help answer questions such as these.

Sometimes it's convenient to refer to evolution as "descent with modification." This conveys a different impression of evolution than the minimal definition. Descent with modification refers to the long-term consequences of short-term changes within a population. It incorporates additional concepts such as speciation, which is an important part of macroevolution. Paleontologists are one group of scientists who aren't directly concerned with the minimal definition of evolution since they are mostly interested in the history of life. They have to deduce that evolution, in the sense of the minimal definition, has taken place from evidence of phenotypic change in the fossil record.

The bad thing about "descent with modification" is that it's not a very rigorous definition. It doesn't rule out modifications that are not genetic in origin and it doesn't rule out individuals evolving—as opposed to populations.

Many people are confused about the difference between a definition and an explanation. That's why we often see incorrect "definitions" that describe how natural selection works. This is wrong. In order to be useful, a definition has to enable us to distinguish examples of evolution from non-evolution but the definition should be neutral with respect to how evolution occurs. It should not distinguish, for example, between Lamarckian evolution and Darwinian evolution even though we know that one of these explanations is incorrect.

Attempts to define evolution in terms of natural selection are not only logically flawed but scientifically flawed as well. They exclude change due to random genetic drift when every evolutionary biologist agrees that drift is a mechanism of evolution.

Evolving Definitions

In 1997 a group of twenty scientists chaired by Douglas J. Futuyma issued a working draft of a "white paper" on Evolution, Science, and Society. The paper was written on behalf of eight scientific societies who wanted to make a statement about evolution. The initial draft defined evolution as,

Biological (or organic) evolution consists of change (modification) in the hereditary characteristics of groups of organisms over the course of generations. Such groups of organisms, termed populations or species, are formed by division of ancestral populations or species, and the descendant groups then change independently. Hence, in a long-term perspective, evolution is the descent, with modification, of different lineages from common ancestors.

This is a pretty good definition. It includes the minimal definition but adds the idea that long-term evolution is descent with modification. The initial draft definition was modified [final draft] so that on the current website it now reads,

Biological evolution consists of change in the hereditary characteristics of groups of organisms over the course of generations. From long-term perspective, evolution is the descent with modification of different lineages from common ancestors. From a short-term perspective, evolution is the ongoing adaptation of organisms to environmental challenges and changes.

This last sentence is really unfortunate. These twenty scientists have now agreed to a definition that specifically mentions the mechanism of adaptation. This is not how one should define evolution. One wonders whether they mean to exclude random genetic drift or whether they simply lost sight of their goal in trying to work out a compromise definition.

The Gene Centrist Objection

Ernst Mayr wrote an entire book on the subject of this little essay. One might expect some insight from one of the original founders of the Modern Synthesis but, unfortunately, we aren't going to get any help from Mayr. On page 157 he says,

Evolution in sexually reproducing organisms consists of genetic changes from generation to generation in populations, from the smallest local deme to the aggregate of interbreeding populations in a biological species.

Ernst Mayr (2001) What Evolution Is, Basic Books, New York p.157

This is good stuff. It restricts the changes to genetic changes and it clearly identifies the population as the unit that evolves. There's no mention of any particular mechanism. But—and you knew there was going to be a "but" didn't you?—good things never last. In his chapter on macroevolution Mayr describes the work of his colleagues Rensch and Simpson. These workers were able to study macroevolutionary events without referring to allele frequencies in a population. Mayr coments,

This approach was consistent with the modern definition of evolution as a change in adaptedness and diversity, rather than a change in gene frequencies, as suggested by the reductionists.

Ernst Mary (2001) What Evolution Is, Basic Books, New York p.189

Consistency is not one of the hallmarks of Ernst Mayr's writings. That's why he can propose two conflicting definitions in the same book, even a book that's devoted to the topic of defining biological evolution! Nevertheless, Mayr does highlight two different objections to the minimal definition that I am defending.

First, Mayr wants a definition that restricts evolution to the mechanism of adaptation. This is a lost battle. There may have been a time in the 20th century when a majority of biologists rejected random genetic drift and other non-adaptationist forms of evolution but that time is long gone. Mayr was one of the last hold-outs. Besides, as I mentioned above, it isn't appropriate to restrict the definition of evolution to a particular mechanism even if you strongly believe that it's the only possible mechanism. That's not how you define something.

Second, Mayr doesn't like reducing evolution to the level of the gene. This charge of reductionism is more interesting. In spite of the fact that Mayr was one of the founders of the Modern Synthesis, he never had much respect for genes and population genetics, or "bean-bag genetics" as he called it. He makes this point very strongly in the preface to his book.

... most treatments of evolution are written in a reductionist manner in which all evolutionary phenomena are reduced to the level of the gene. An attempt is then made to explain the higher-level evolutionary process by "upward" reasoning. This approach invariably fails. Evolution deals with phenotypes of individuals, with populations, with species; it is not a "change in gene frequencies." The two most important units in evolution are the individual, the principle object of selection, and the population, the stage of diversifying evolution.

Ernst Mary (2001) What Evolution Is, Basic Books, New York p.xiv

I happen to agree with some of those who criticize the extreme reductionist views of scientists like Richard Dawkins but in this case Mayr has it all wrong. When we define evolution as a change in the heritable characteristics of a population we are not reducing evolution to the level of the gene. We are merely stating that populations don't evolve unless they undergo genetic changes. This is not controversial in spite of Mayr's objection. He is confused about the difference between a definition of evolution and a proposed mechanism of change—as was obvious in his attempt to include adaptation. This is a remarkable error in a book called "What Evolution Is."

The Minimal Definition and Macroevolution

The minimal definition of evolution is not inconsistent with Hierarchical Theory and a focus on macroevolution as opposed to microevolution. This point is worth emphasizing since the minimal definition has often been criticized for excluding lots of evolution that takes place at higher levels. Stephen Jay Gould—no fan of reductionism and no stranger to hierarchical theory—addressed this problem in his last anthology.

The Darwinian principle of natural selection yields temporal change—"evolution" in the biological definition—by a twofold process of generating copious and undirected variation within a population, and then passing only a biased (selected) portion of this variation to the next generation. In this manner, the variation within a population at any moment can be converted into differences in mean values (such as average size or average braininess) among successive populations through time.

Gould, S.J. (2002) "What Does the Dreaded 'E' Word Mean Anyway?" in I HAVE LANDED Harmony Books, New York p. 246

The purpose of his essay was to point out the fundamental difference between this biological definition and the common vernacular meaning of the word "evolution." (I wish he hadn't used the word "selected" in his definition since it implies natural selection and Gould knows that there are other mechanisms.) Gould points out that other sciences, such as astronomy, use the word "evolution" in a very different sense—one that is actually closer to the original nineteenth century meaning. The vernacular meaning carries an implication of purpose and direction that is entirely absent from the biological definition of changes in the heritable characteristics of a population over time. This is why Darwin never used the dreaded "E" word.

Gould argues that an understanding of the true importance of the biological definition is absolutely essential to understanding why the general public is confused. He is especially concerned about emphasizing the lack of progress and direction in the definition of biological evolution. He advocates that scientists owe it to the general public to teach the biological definition.

I don't mention these differences to lament, or complain, or to criticize astronomical usage. After all, their concept of 'evolution' remains more faithful to etymology and the original English definition; whereas our Darwinian reconstruction has virtually reversed the original meaning. In this case, since neither side will or should give up its understanding of "evolution"—astronomers because they have retained an original and etymologically correct meaning, evolutionists because their redefinition expresses the very heart of their central and revolutionary concept of life's history—our best solution lies simply in exposing and understanding the legitimate differences, and in explaining the good reasons behind the disparity of use.

In this way, at least, we may avoid confusion and the special frustration generated when prolonged wrangles arise from mis-understandings about words, rather than genuine disputes about things and causes in nature. Evolutionary biologists must remain especially sensitive to this issue, because we still face considerable opposition, based on conventional hopes and fears, to our emphasis on an unpredictable history of life evolving in no inherently determined direction. Since astronomical 'evolution' upholds both contrary positions—predictability and directionality—evolutionary biologists need to emphasize their own distinctive meaning, especially since the general public feels much more comfortable with the astronomical sense—and will therefore impose this more congenial definition upon the history of life if we do not clearly explain the logic, the evidence, and the sheer fascination of our challenging conclusion.

(ibid p. 250-252)

I agree with Gould. That's why I think it's important to explain the real biological definition of evolution as a change in the heritable characteristics of a population over time. We can explain that this is a minimal definition, and that there's more to evolution than this, but we shouldn't back away from the real meaning of the term since it conveys some important messages. If we cave into pressure from the general public to make evolution into something they can understand, with all their biases, then we will have lost the battle before we even begin.

The amazing thing about the minimal definition of biological evolution is that it doesn't carry any baggage concerning the history of life or its future. As soon as we try to define evolution in terms of the historical record, we run into all kinds of problems because we confuse evolution as a process with evolution as a history of life. The scientific definition attempts to describe the minimum thing that might be called evolution. We know that the history of life is more complicated than this and we know that evolutionary theory encompasses other things such as the formation and extinction of populations. There is no conflict between the minimal definition of evolution as a change in the genetic composition of populations and macroevolution. Gould understands this.

[This is a slightly modified version of an essay that appears here. An earlier version is on the TalkOrigins Archive.]

My Library Card

 
Everybody else is doing it. Here's my library card. Make your own at Catalog Card Generator.

Canadian Scientists Show that Speaking Two Languages Protects You from Dementia

 
Biology News Net reports that a Canadian study shows bilingualism has protective effect in delaying onset of dementia by four years. It's total nonsense, of course, ... but what the heck, it makes good press, n'est-ce pas?

I'm embarrassed that so-called scientists at my university are allowing such rubbish to be published in a press release. The clear implication is that there's something about speaking two languages that delays the onset of dementia and Alzheimer's. Correlation is not the same as cause and effect. Repeat after me, a correlation does not necessarily identify a cause.

Update: Here's the original press release from the Baycrest Centre.

Little Mosque on the Prairie

 
There's a new sitcom on Canadian television called "Little Mosque on the Prairie." The first show aired on Wednesday and it's already attracting a lot of attention. See Monado's review at Little Mosque on the Prairie starts this week.

Does Disbelieving Evolution Reflect a Lack of Understanding of It?

 
Bill Dembski is troubled by the latest report in Science that shows a correlation between acceptance of evolution and education. [See PZ Myers' summary on Pharyngula.] The data suggests that the more educated you become the more likely you are to accept evolution. In other words, the data suggests that IDiots are, well, idiots.

You can see why Dembski is upset [Does understanding coerce belief?]. The truth hurts. Dembski then goes on to give us a good demonstration of the negative correlation between intelligence and belief in intelligent design.

But why should disbelieving evolution reflect a lack of understanding of it? Alternatively, does understanding evolution automatically force one to believe it? I remember speaking at the University of Toronto in 2002 when a biologist challenged me about how holding to ID renders one a nonscientist. I asked him if that disqualified Isaac Newton from being a scientist. His instant response was, “but he didn’t know about evolution.”

I don't know if Dembki is referring to me or to one of my colleagues who was at the meeting. I recall accusing Dembski of stupidity and of not being a good scientist, but there were so many of us making the same point that I don't know which one Dembski remembers. (Dembski has mentioned this meeting many times. It must have been very traumatic for him.)

At the risk of boring anyone with an IQ over 80, let me make the point that Dembski is deliberately missing. In 2002, if you rejected evolution you were an idiot. That's because the evidence for evolution is overwhelming. The same correlation holds today, only more so.

To answer the question posed in the title; yes, disbelieving in evolution reflects a lack of understanding of evolution. That's an empirical observation. There are very, very few IDiots who understand evolution. (Don't believe me? Read Uncommon Descent and Evolution News & Views.) Dembski sure aint' one of them. He didn't understand the basic principles of evolutionary theory in 2002 and he's given no indication of having learned anything since then.

Newton didn't know about evolution so he couldn't have rejected it. He wasn't stupid and he wasn't a bad scientist. He also didn't know about general relativity and plate tectonics but that didn't mean he was stupid either. If Newton were alive today you can be sure he would accept evolution, continental drift and general relativity. In the 21st century, anyone who rejects these fundamental concepts in science doesn't deserve to be called a scientist.

Barack Obama Is a Closet Muslim

 
Friday's Urban Legend: FALSE

There's an email circulating that Barack Obama was educated as a Muslim in a Wahabbi school in Indonesia. According to the email message ("The Enemy Within"), his step-father, Lolo Soetoro, was a Muslim who brought up Obama in the Muslim tradition. (The truth is that Obama's mother was an atheist and so was his biological father. His step-father was a non-practicing Muslim.)

Later on as an adult, Obama joined the United Church of Christ in order to convince voters that he was a Christian but he's still an ideological Muslim, according to the email message.

The take-home message is FALSE according to snopes.com [The Enemy Within] but there are elements of truth in the email message. It's worth reading the entire snopes article in order to understand Obama's religious views. This is the sort of thing that's going to come out during the Presidential campaign and if the snopes article is accurate, there's trouble brewing.

Stem Cell Debate in the USA

 
Furriners like me sometimes have a hard time following American politics. Take the debate over funding stem cell research, for example. America doesn't do it. Bush is very much against changing the law to permit development of new lines of stem cells. It's against his religion.

Mathew Nesbit has written an excellent summary of the situation over at Skeptical Inquirer [Political Communication in the 2007 Stem Cell Debate]. He follows up with a report on his blog [STEM CELL BILL PASSES THIRTY-SEVEN VOTES SHORT OF VETO OVERRIDE]. Apparently this is another fight over which "power" (President or Congress) is supposed to make laws. You'd think the Constitution would be clear about those things.

Now, if only someone could explain who's supposed to be in charge of making war ..... people seem to be confused about that as well.

Human Races Populations

 
I get pretty sick of hearing that there's no such thing as "races" in the species Homo sapiens. RPM has revived the controversy in More About Human Populations. Read the comments as well.

Apparently, it's more politically correct to refer to human "populations" and avoid the r-word.

We Really Are Quite Small

 

Olfactory Receptor Genes

 
The human genome contains 388 different olfactory receptor (OR) genes. These genes encode olfactory receptors, the molecules that detect odors [A Sense of Smell: Olfactory Receptors]. Our genome also has 414 olfactory receptor pseudogenes. These are stretches of DNA that resemble functional genes but they have accumulated mutations rendering them non-functional. In some cases, a single mutation has disrupted the open reading frame—these pseudogenes have recently evolved from functional genes. In most cases the olfactory receptor pseudogenes have multiple mutations, including extensive insertions and deletions, indicating that these pseudogene lost functionality millions of years ago.

None of the olfactory receptor genes have introns. This is a huge advantage because it is much easier to recognize functional genes and pseudogenes by scanning the genome.

The human genes and pseudogenes are clustered. Some clusters contain dozens of genes while others have only a few. There are 95 different clusters spread over all chromosomes except chromosome 20 and the Y chromosome. The first figure (below) is from a review by Niimura and Nei (2006). It shows the locations of the OR gene clusters. The vertical lines above the chromosome indicate the number of functional genes at that position—the taller the line the more genes. Lines below the chromosome indicate pseudogenes at that position.


A phylogenetic tree of the 388 functional OR genes reveals two main classes. All 57 class I genes are clustered together on chromosome 11. The class II genes can be subdivided into several subgroups labelled A to S in the figure below (Fig. 2 from Niimura and Nei (2006)). Several clusters are shown in order to illustrate the fact that genes of the same subclass tend to cluster together. Large letters indicate functional genes and small letters indicate related pseudogenes. Genes below the line are transcribed in the opposite direction from those above the line. (X identifies unclassified genes.)

Adjacent, closely related genes that are transcribed in the same direction are said to be tandemly duplicated, indicating that they probably arose by gene duplication. For example, most of the subclass A genes in cluster 11.11 probably resulted from repeated duplication of single A-type gene at that site.

The mouse genome contains 1037 functional genes and 354 pseudogenes in 69 clusters. Almost all of the clusters map to related clusters in the human genome. If we look at the relationship between the clusters on human chromosome 11 (Hs11) and mouse chromosome 2 Mm2), we see that the mouse cluster is larger and parts of it have been split up into four different clusters in humans. Nevertheless, the general order of genes is similar in mice and humans. There are more mouse OR genes, as expected. It has long been known that genes on human chromosome 11 are related to genes on mouse chromosome 2. (The figure is from Niimura and Nei (2006)).

How did this large gene family evolve? It seems clear that the common ancestor of mice and humans must have had many OR genes. It appears that the number of genes has probably changed considerably in one, or both, lineages. Why, and how, do some genes become inactivated? Is evolution of gene families due to natural selection or someting else? See "The Evolution of the Olfactory Receptor Gene Family" in tomorrow's posting.)

Niimura Y. and Nei M. (2006) Evolutionary dynamics of olfactory and other chemosensory receptor genes in vertebrates. J. Hum. Genet. 51:505-17

Cut and Run

 
"Cut and run" is straight talk for a military strategy otherwise known as "strategic redeployment" or "tactical victory." In some circles it's called "defeat" but that's a little too close to the truth to be acceptable.

The cut and run strategy means withdrawing all troops from Iraq and Afghanistan immediately. Not next year, and not next month. Tomorrow would be good. I'd vote for that.

Why should our troops stay in the Middle East? The most common argument in favor of continued occupation is that we broke Afghanistan and Iraq and it's now up to us to stay there and fix them (The Pottery Barn Rule).

This is a strange argument if you think about it for more than a second—a length of time that seems to just about cover the average attention span of neocon war hawks. What we've done in Afghanistan and Iraq is to destabilize those countries by removing a strong central government that provided peace and security to the majority of their citizens—albeit, at the expense of freedom and, in many cases, lives. Not perfect but better than what they've got today. That's why 80% of Iraqis preferred the life they had before the invasion (Iraqis say they were better off under rule of Saddam Hussein).

By staying there and propping up a Quisling "democracy" that's incapable of maintaining law and order, we are encouraging and protecting the local warlords and private militia. We are creating an environment that promotes a low-level civil war that will never produce a victory for either side. In other words, our troops might be contributing to the problem, not the solution. Furthermore, the Pottery Barn Rule runs counter to the stated goal of the invasions, which were supposed to allow the citizens to choose their own form of government. They own it; they should fix it.

The proper strategy is to withdraw. Cut your loses and get out as fast as possible. That's the only honorable way out of a losing strategy. Just like Vietnam. If we don't leave now, we'll be having this debate a year from now, only the countries will be even more broken. (I said the same thing a year ago, and I expect to be saying it in 2008 and 2009 and ....)

Thousands of allied soldiers died during the invasions and the subsequent occupations of Afghanistan and Iraq. Many people are opposed to the idea to admitting we made a mistake because of the extreme sacrifices that these soldiers have made. They ask the tough question, "Does this mean that all those men and women died in vain?"

Yes. That's one of the unfortunate consequences of making a bad decision. While there was some justification for invading Afghanistan in 2001, we have overstayed our welcome and it's time for the Afghanis to settle their own internal squabbles.

But there was never any rational justification for invading Iraq. Most of us know that by now. Everyone who has died there has died in vain—including tens of thousands of innocent Iraqi citizens. It's sad to have to admit this, especially when talking to the friends and loved ones of fallen soldiers, but pretending it ain't so isn't going to help. You can't use the fact that soldiers died unnecessarily as an excuse to send more troops into battle.

Happy Sir John A. Macdonald Day!

 
Sir John A. Macdonald became the very first Prime Minister of Canada on July 1, 1867. He is one of the Fathers of Confederation. (There were no mothers back then.)

Sir John A. was a hard-working, hard-drinking immigrant. He was born in Glasgow, Scotland in 1815 and he celebrated his birthday on January 11th. There are many stories about his drinking. Here's what Wikipedia says,

Macdonald was well known for his wit and also for his alcoholism. He is known to have been drunk for many of his debates in parliament. Two apocryphal stories are commonly repeated; the first describing an election debate in which Macdonald was so drunk he began vomiting violently on stage while his opponent was speaking. Picking himself up Macdonald told the crowd, "see how my opponent's ideas disgust me." The second version has Macdonald responding to his opponent's query of his drunkenness with "It goes to show that I would rather have a drunk Conservative than a sober Liberal."

In typical Canadian fashion, we honour our most famous Canadian (he's on the $10 bill) by going off to work. There's no holiday for Canadians on January 11th. You celebrate by raising a glass of scotch when you get home in the evening, or maybe at lunch.

Now, don't get me wrong. I appreciate the fact that our government at least gives us a day off to celebrate the birthdays of two other famous people: Queen Victoria and Jesus. But they're not Canadians.

SBC - NC'07

 
I'm going to the 2007 North Carolina Science Blogging Conference. Are you?

Nobel Laureates: Richard Axel and Linda B. Buck

 
The Nobel Prize in Physiology or Medicine 2004.

"for their discoveries of odorant receptors and the organization of the olfactory system"

Richard Axel and Linda B. Buck won the Nobel Prize for discovering olfactory receptor genes. They showed that mice have about 1000 different olfactory receptor genes, each one encoding a different receptor.

You can watch a video recording of the acceptance speeches or read them as PDF documents [Axel Lecture][Buck Lecture].

Oh My God!

 
This is a photograph taken by Zarna, one of my students who just came back from a trip to India.

The Difference Between Rationalism and Superstition

 
Bill Dembski's Comments About Comments.

I don’t plan on policing or editing comments. If you post a comment that I don’t think is productive, I’ll probably not just eliminate your comment but you from this blog (which, given the way WordPress handles comments, means all your comments will be removed). So if you have any doubts about whether I’m going to react negatively to your comments, back them up — I won’t. Note also that I’ve had it happen where someone ingratiates himself with me and then turns. Bait and switch is a sure way to be banned from commenting here.

My policy on comments: anyone can post whatever they like, especially if they disagree. There will be no censorship of ideas on Sandwalk.

Darwin's Grave

 
Mike Dunford visited Westminster Abbey today and stood at the place where Charles Darwin is buried. He wonders what an agnostic should do under those conditions. See A Strange Moment.

Here's a photo of Darwin's final resting place in Westminster Abbey.