How Does Streptomycin Work?

Streptomycin is a powerful antibiotic that inhibits growth of bacteria while having very little effect on eukaryotes. It blocks protein synthesis by binding to the bacterial ribosome.

Let's review the steps of protein synthesis. The three steps are initiation, where the ribosome and factors are assembled at the start codon on the messenger RNA (mRNA); elongation, where the polypeptide chain elongates as the translation machinery moves along the mRNA; and termination, where the assembly falls apart and the completed polypeptide chain is release.

During the elongation phase there are three sites at the interface between the ribosome and the mRNA where transfer RNAs (tRNAs) can bind. The P site holds the peptidyl-tRNA molecule. The growing polypeptide chain is bound to the tRNA molecule that contributed the last amino acid. The A site binds the incoming aminoacylated tRNA molecule. The anticodon of this aa-tRNA is complementary to the mRNA codon located in the A site. Insertion of the correct aa-tRNA is mediated by elongation factor Tu (in bacteria)..

Formation of the peptide bond then occurs in a reaction catalyzed by peptidyl transferase—an enzymatic activity of the ribosomal RNA in the ribosome. When this happens the growing peptide chain (grey balls) is transferred to the tRNA that was in the A site.

The next step is to shift the ribosome relative to the mRNA bringing the peptidyl-tRNA molecule into position in the P site and freeing up the A site for a new amimoacyl tRNA to bind. This step is called translocation and it is mediated by elongation factor G (EF-G). During the translocation the uncharged tRNA is temporarily moved to the exit site (E site) before being released.

Streptomycin inhibits the translocation step by binding to the small subunit ribosomal RNA and blocking the activity of EF-G.

Here's a picture (below) of what the bacterial ribosome looks like. Most of it is RNA (yellow chain) folded into a complex conformation. The three dimensional structure is stabilized by a number of small proteins (orange + blue) bound to the outer surface of the RNA. One of these proteins is S12, located in the grove where mRNA binds to the ribosome. S12 stabilizes the RNA three-dimensional structure to which streptomycin binds.


Bacteria rapidly develop resistance to streptomycin, which explains why it isn't as effective today as it was when it was first introduced in the 1940s. One of the common resistance mutations affects ribosomal protein S12. The mutant protein is able to maintain the proper RNA conformation in the presence of streptomycin and this allow translocation to proceed.

---

Thesis Defense - 35th Anniversary

 
Today is the 35th anniversary of my Ph.D. oral defense. The event took place in the Department of Biochemical Sciences at Princeton University back in 1974.

It began with a departmental seminar. When the seminar was over I retired with my committee to a small classroom for the oral exam.

I don't remember everyone who was on my committee. My Ph.D. supervisor (Bruce Alberts) was there, as was my second reader, Abe Worcel. I know Uli Laemmli was there and so was Arnie Levine. I'm pretty sure the external member of the committee was Nancy Nossal from NIH in Bethesda, MD (USA). It's a bit of a blur after all these years.

I remember being fairly confident about the exam. After five and a half years I was pretty sure that everyone on my committee wanted to get rid of me and the easiest way to do that was to let me pass. Bruce stood to gain $3000 per year of research money and Uli was going to get back the basement of his house where Ms. Sandwalk and I had been living for the past month.

The toughest questions were from Uli Laemmli, which should not come as a surprise to anyone who knows him. He has this annoying habit of expecting people to understand the basic physics and chemistry behind the biochemical sciences. Fortunately, my inability to answer most of his questions didn't deter him from voting to pass me.

This photograph was taken at a party that evening. I look pretty calm at that point but this may have had a lot to do with the various refreshments that were being served.

The amazing thing about the photograph—as I'm sure you all agree—is how little I've changed since then—apart from a haircut.

Back in those days we didn't spend a lot of time writing a thesis. I started in the middle of January and the entire process of writing and defending took nine weeks. My thesis was bound and delivered to the library about one week after the Ph.D. oral.

The second page of my thesis has only three words on it. It says, "To Leslie Jane." This is Ms. Sandwalk. She really should have her name on the cover 'cause I couldn't have graduated without her. Typing my thesis was only one of her many contributions. There are 257 pages in my thesis and she typed every one. As a matter of fact, she typed them twice, one draft and then the final version.

The figures in my thesis were all hand drawn. I've included one (below) to illustrate what I was doing during those five and a half years.

The Alberts lab was interested in DNA replication during bacteriophage T4 infections of E. coli. We knew that replication was carried out by a complex protein machine that assembled at a replication fork but we didn't know all the players or what they did.

The T4 proteins required for DNA replication were known from genetic studies. The most important genes were genes 30 (ligase), 32 (single-stand DNA binding protein), 41, 43 (DNA polymerase), 44, 45, and 62. The products of the unknown genes were called 41P, 44P, 45P and 62P.

We wanted to purify and characterize those proteins; my target was the product of gene 41, or 41P.

We had a cool assay, developed mostly by a postdoc in the lab named Jack Berry. What we did was to prepare a cell lysate from cells that had been infected by bacteriophage carrying an amber mutation in one of the genes. This lysate could not support DNA synthesis, as measured by incorporation of ³²P nucleotides, unless we added back the missing component. This is the basis of an in vitro complementation assay that worked for each of the unknown proteins.

In my case, I used traditional protein purification methods to isolate fractions of proteins and them tested them for activity in the complementation assay. The figure below shows the elution profile of proteins bound to a hydroxylapatite column. The peak centered on fraction 61 is the activity of the complementation assay. It indicates that 41P elutes early as a sharp peak in the elution profile.



The complementation assay doesn't tell us anything about the function of 41-protein, only that it complements an extract that's deficient in 41P. Strictly speaking, it doesn't even tell us that the activity is due to the product of gene 41 since it could be something else that complements in vitro.

Fortunately we had another way of identifying 41P. I started my purification with extracts from 17 liters of infected cells. To this I added extracts from cells that had been labeled with radiaoctive amino acids. One batch was from a wild-type infection where all T4 proteins are labeled with ¹⁴C amino acids. The other batch is from an infection with an amber mutation in gene 41. In this case every protein except 41P is labeled with ³H amino acids.

You can adjust the settings on a scintillation counter so they distinguish between ¹⁴C and ³H but there's some overlap. The equations for calculating the contribution of each isotope in each window are relatively simple. All you need are good standards to get the distribution. One of the most fun things I did as a graduate student was to write a computer program (in Fortran) that did these calculations automatically and plotted them on a plotter. This was back in the time when computers were housed in large separate buildings and required dozens of people to look after them.

If you look of the elution profile in the figure you'll see there's an excess of ¹⁴C over ³H in the same fractions where the complementation activity is located. What this means is that the wild-type extract has a protein at that position that's not found in the am41 extract. It's another way of identifying the product of gene 41.

The double label technique was useful 35 years ago but nobody does it anymore. It was fun while it lasted.

(I never did figure out what 41P did during DNA replication but a few years after I left a postdoc identified 41P as a helicase—an enzyme that unwinds DNA ahead of the replication fork. The enzyme is now called gp41 for "gene product.")

---

Old Tools

 

---

Old Tools

 

---

What's the best way to describe a graduate student?

 
The controversy over the 1952 Nobel Prize reminds me that we haven't had a poll in a long time. Check out the poll in the left-hand sidebar. How would you describe a graduate student?

You must answer by April Fool's Day.

---

Nobel Laureate: Selman Waksman

 

The Nobel Prize in Physiology or Medicine 1952

"for his discovery of streptomycin, the first antibiotic effective against tuberculosis"

Selman Abraham Waksman (1888 - 1973) won the Noble Prize in 1952. The award was for discovering streptomycin.

Waksman was a soil microbiologist at Rutgers University in New Jersey (USA). In the 1930s, after the success of penicillin, he decided to change the focus of his research and look for more antibiotics. He reasoned that soil microorganisms should be a good source of novel anti-bacterial drugs.

Streptomycin was the most famous of the many antibiotics discovered in Waksman's lab. It was largely due to the dedicated work of a graduate student, Albert Schatz, who first identified streptomycin's potent effect on gram negative bacteria in October 1943. Over the next few years, Waksman became famous for discovering streptomycin and Schatz was all but forgotten.

In 1950, Schatz sued his former supervisor for recognition, and a share of the royalties. The case was settled out of court with Rutgers agreeing that Schatz and Waksman would be identified as co-discoverers of streptomycin. Schatz received a share of the royalties.

In spite of this settlement, the Nobel Prize committee awarded the prize to Wakesman and not to Waksman and Schatz. This was mildly controversial at the time but didn't qualify as a major scandal. It seems more egregious today.

The issue is part of a continuing controversy about how to attribute recognition when graduate students are working under the direction of their supervisors. There's no better way to start a fight than to bring this up with a group of graduate students. Are they apprentices, slaves, or collaborators?

I am indebted to Philip Johnson of York University (Toronto, Canada) for alerting me to the controversy and for sending along this excellent article about Albert Schatz.

Waksman does not specifically mention Schatz's contribution in his Nobel lecture but he is mentioned in the presentation speech (see below) in an obvious attempt to minimize his contribution. Knowing what we know now, should the Nobel Prize website be modified to include a discussion of the controversy? I think it should.

THEME:
Nobel Laureates

In 1940 Dr.Waksman and his collaborator had succeeded in isolating the first antibiotic, which was called «actinomycin» and it was very toxic. In 1942 another antibiotic was detected and studied, called «streptothricin». This had a high degree of activity against many bacteria and also against the tubercle bacillus. Further studies revealed that streptothricin was too toxic. During the streptothricin studies Dr. Waksman and his collaborators developed a series of test-methods, which turned out to be very useful in the isolation of streptomycin in 1943.

Encouraged by the discovery of streptothricin and stimulated by the triumphal development of penicillin treatment, the research team headed by Dr.Waksman continued their untiring search for new antibiotic-producing microbes. Before the discovery of streptomycin no less than 10,000 different soil microbes had been studied for their antibiotic activity. Dr. Waksman directed this work and distributed the various lines of research among his young assistants. One of these was Albert Schatz, who had previously worked with Dr. Waksman for 2 months and in June 1943 returned to the laboratory. Dr. Waksman gave him the task of isolating new species of Actinomyces. After a few months he isolated two strains of Actinomyces which were shown to be identical with Streptomyces griseus, discovered by Dr. Waksman in 1915. In contrast to the previous one the rediscovered microbe was shown to have antibiotic activity. To this antibiotic Dr. Waksman gave the name «streptomycin». He studied the antibiotic effect of streptomycin with Schatz and Bugie and found that it was active against several bacteria including the tubercle bacillus. These preliminary studies were completed in a relatively short time, thanks to the clear principles which had been set out previously by Dr. Waksman for the study of streptothricin.

---

The images of the Nobel Prize medals are registered trademarks of the Nobel Foundation (© The Nobel Foundation). They are used here, with permission, for educational purposes only.

Making Tracks

 
Look at the photo on the right. Do you know why this is an important discovery? Did you know you could win a case of beer for discoveries like this?

Find the answer on Catalogue of Organisms: More Crunchy Scleritome Goodness. Find out more about the little "problematic" animal in the photo.

---

Stasis Is Data, says Don McLeroy

 
Don McLeroy is a creationist dentist from Texas. His claim to fame is that he is the current chair of Texas State Board of Education. That board is trying to insert creationist-friendly standards into the state curriculum.

Today, the Austin American Statesman published an op-ed piece by McLeroy in which he defends creationism: Enlisting in the culture war.

It makes for amusing reading. I want to address one particular issue that illustrates how creationists misunderstand the science they criticize. It vividly points out what we are up against. The opponents of science don't even take the time to understand what they oppose.

Let's start by looking at the chart (right). It illustrates the now-famous pattern of punctuated equilibria as detected in the fossil record. What it shows is that speciation by cladogenesis (splitting) is associated with morphological change. When a new species evolves from a parent species it does so quite rapidly. After the speciation event (horizontal lines on the chart) the two species exist side-by-side in the same environment for millions of years without significant morphological change. Eventually they becomes extinct as shown by the termination of the vertical lines.

Species exist for 5-10 million years. During most of that time they do not change very much. This is what Eldredge and Gould called "stasis." The entire pattern is one of stasis interrupted by short periods of evolution at the time of speciation, or "punctuated equilibria."

The patterns in the fossil record raise interesting questions. One of the most important is whether it represents the normal pattern of evolution or whether it is confined to a minority of clades. What causes stasis? Why is change associated with cladogenesis? Why do species go extinct? All of these are widely discussed in the scientific literature.

None of the questions is a challenge to evolution. Punctuated equilibria is a pattern that might lead to an extension of evolutionary theory.

Now let's look at what McLeroy writes in his op-ed piece.
It is absolutely safe to say that if you meet somebody who claims not to believe in evolution, that person is ignorant, stupid or insane (or wicked, but I’d rather not consider that).

Richard Dawkins

The next step in resolving this controversy is simply to use the scientific method to weigh in on the issue of evolution. Consider the fossil record. What do we actually observe? What are the data?

Stephen Jay Gould stated: "The great majority of species do not show any appreciable evolutionary change at all. [This is called 'stasis.'] These species appear ... without obvious ancestors in the underlying beds, are stable once established and disappear higher up without leaving any descendants."

"...but stasis is data..."

Once we have our observations, we can make a hypothesis. The controversial evolution hypothesis is that all life is descended from a common ancestor by unguided natural processes. How well does this hypothesis explain the data? A new curriculum standard asks Texas students to look into this question. It states: "The student is expected to analyze and evaluate the sufficiency or insufficiency of common ancestry to explain the sudden appearance, stasis, and sequential nature of groups in the fossil record." It should not raise any objections from those who say evolution has no weaknesses; they claim it is unquestionably true.

I don't see a problem with explaining punctuated equilibria to high school students, assuming, of course, that Texas has competent science teachers. It would teach students about critical thinking and reinforce some of the fundamental concepts of evolution.

This isn't what McLeroy has in mind. I think it's very clear what he thinks about punctuated equilibria. He thinks it supports some (unstated) version of creationism. The point of his op-ed piece is to convince his supporters that scientists are trying to hide important evidence for creationism.

I'm assuming that McLeroy simply doesn't understand the science behind punctuated equlibria, or evolution, and that's why he misrepresents it in his article. This means that McLeroy is ignorant, stupid, or insane. There's another possibility but we won't consider that.

Here's something I found on the Wikipedia website for Don McLeroy.

In 2009, McLeroy spoke at a board meeting with several quotes from scientists in an attempt to discredit evolution. The quotes were later revealed by a biology teacher to be incomplete, out of context, or incorrect taken from a creationist website.[10][11] McLeroy said that while "some of the material was taken from the creationist site, he added: “A lot of the quotes I did get on my own.”

You may be wondering if these out-of-context quotations include anything on punctuated equilibria or stasis. It would be embarrassing to find out that McLeroy repeated those misleading quotations only a few weeks after learning that they were wrong. Here's the list: Collapse of a Texas Quote Mine.

Pray for Texas. The decision on education standards will be made any day now.

---

[Image Credit: Punctuated Equilibrium and Patterns from the Fossil Record]

Old Tools

 

---

I'm Beginning to Really Like Jerry Coyne

 
That's because he writes things like Must we always cater to the faithful when teaching science?.

As long as I have been a scientist, I have lived with my colleagues’ view that one cannot promote the acceptance of evolution in this country without catering to the faithful. This comes from the idea that many religious people who would otherwise accept evolution won’t do so if they think it undermines their faith, promoting atheism or immoral behavior. Thus various organizations promoting the teaching of evolution, including the National Academy of Sciences and the National Center for Science Education, have published booklets or websites that explicitly say that faith and science are compatible. In other words, that is their official position. The view of many other scientists that faith and science (or reason) are incompatible is ignored or disparaged. As evidence for the compatibility, the most frequent reason cited is that many scientists are religious and many of the faithful accept evolution. While this proves compatibility in the trivial sense, it doesn’t show, as I’ve pointed out elsewhere, that the two views are philosophically compatible.

....

Because of this, I think that organizations promoting the teaching of evolution should do that, and do that alone. Leave religion and its compatibility with faith to the theologians. That’s not our job. Our job is to show that evolution is true and creationism and ID aren’t. End of story.

I agree. Organizations like NCSE, AAAS, and the National Academies should just talk about science. As soon as they start to say that science and religion are compatible they are misrepresenting a huge number of scientists and stepping outside their mandates.

---

Monday's Molecule #114: Winners

 
UPDATE: The molecule is streptomycin, 5-(2,4-diguanidino-3,5,6-trihydroxy-cyclohexoxy)- 4-[4,5-dihydroxy-6-(hydroxymethyl) -3-methylamino-tetrahydropyran-2-yl] oxy-3-hydroxy-2-methyl-tetrahydrofuran-3-carbaldehyde. Streptomycin inhibits protein synthesis in bacteria. The Nobel Laureate is Selman Waxman.

This week's winners are Bill Chaney of the University of Nebraska and Elvis Cela of the University of Toronto.

---

Identify this molecule and briefly describe its function. You must supply the common name and one of the the formal IUPAC names.

I'm looking for the Nobel Laureate who discovered this molecule.

The first person to identify the molecule and the Nobel Laureate wins a free lunch at the Faculty Club. Previous winners are ineligible for one month from the time they first won the prize.

There are seven ineligible candidates for this week's reward: Guy Plunket III from the University of Wisconsin, Deb McKay of Toronto, Maria Altshuler of the University of Toronto, David Schuller of Cornell University, Adam Santoro of the University of Toronto, Dima Klenchin from the university of Wisconsin, and Alex Ling from the University of Toronto.

Dima has offered to donate a free lunch to a deserving undergraduate so I'm going to continue to award an additional free lunch 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 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. I reserve the right to select multiple winners if several people get it right.

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

---

Let the Physicists Fix the Economy.

 
Chad Orzel at Uncertain Principles has an interesting idea on how to fix the current economic crisis. He thinks all traders and financial wizards should be fired because Physics Can Fix This.

And, seriously, do you really think that these transactions are too complicated for physicists to figure out? We're talking about people who have spent the last several years thinking about folding and twisting strings in eleven dimensions. Unless the transaction records are all encrypted in some private cipher, they'll have no trouble figuring it out. And even if they are encrypted, that will only slow things down a little-- given what we know about the rocket scientists on Wall Street, the cipher key is probably written on a Post-It stuck to the computer. With a magnet.

Better yet, they'll be cheap. We're talking about theoretical physics grad students and post-docs-- most of them are currently working for less than Vikram Pandit spends on shoes. The pre-bonus salary given to a typical financial executive is more money than they can reasonably expect to make in their current line of work. It'll be a major blow to the over-priced restaurant industry in lower Manhattan, but they'll rebound once they learn to mark up Ramen noodles a thousand percent.

And best of all, we don't have to worry about them getting greedy and wrecking the entire global economy in order to make some short-term gains. We're talking about people who, to this point, have completely sacrificed their financial well-being in pursuit of higher mathematical truth. They're used to working toward the long-term success of abstract goods.

Sounds good to me. It can't possibly be any worse.

---

Medical Care? - Canada Bad, America Great

 
OldFart is an American doctor who sometimes posts on M.D.O.D.. Here's what (s)he wrote last Friday [Natasha Richardson R.I.P.].

How do you think Natasha Richardson's family likes that socialized medicine in Canada??

Any 3rd year med student or an EMT worth his salt would know she was a set-up for an epidural hematoma. It is an incredibly classic story for it. And so easy to diagnose with an 8 second CT of the brain.

But in Canada I bet she was "put in queue" for a CT scan next week and had to fly to the US in order to get one in a real hospital's ED. But by then she was brain dead.

Still want Hussein's version of medicine here you fuckin' brain dead liberals?? Could save a lot of tax payor's dollars, huh? Everybody could get the "same access" to health care huh?

Just not when it's your family..

My prayers to Ms Richardson's family.

Every civilized country has socialized medicine because they think it's a fundamental right to get medical care without having to worry about how to pay for it. What is it about American doctors that they are so opposed to this concept?

M.D.O.D. is a group blog. Another American doctor, 911doc, has added this update ...

EDITOR'S NOTE: OLDFART POSTED BELOW A FEW HOURS AGO AND SITTING HERE IN BED WITH THE WIFE I LEARNED, IN THAT REPUTABLE MEDICAL JOURNAL 'PEOPLE MAGAZINE', THAT MRS. RICHARDSON HAD INDEED REFUSED TRANSPORT AND MEDICAL CARE AFTER WHAT WAS A MINOR FALL ON A 'BUNNY SLOPE' (ON WHICH SHE WAS NOT WEARING A HELMET).

THOUGH I TOO WONDERED IF THE 'QUEUE UP' PROBLEM WAS AT PLAY HERE IT EVIDENTLY WAS NOT, AND SO WHILE WE WILL NO DOUBT HAVE OTHER OPPORTUNITY TO COMPARE THE ACCESS TO EMERGENCY CARE IN SOCIALIZED COUNTRIES TO THE ACCESS TO EMERGENCY CARE HERE, THIS IS NOT THE CASE TO DO IT WITH.

I WILL ASK THIS QUESTION OF ANY CANADIAN PHYSICIANS WHO HAPPEN BY HOWEVER. HOW QUICKLY CAN ONE GET A CT OF THE BRAIN IN A CASE SUCH AS THIS WHERE THERE APPARENTLY WAS NO OBVIOUS TRAUMA AND THE ONLY COMPLAINT ONE HOUR AFTER THE FACT WAS A WORSENING HEADACHE? HOW ABOUT FOR A INTERNATIONAL CELEBRITY?

I'm also curious. How easy is it to get a CT scan in the first aid station at the bottom of a ski slope in either country? How often are CT scans performed in the small town local hospitals? In the USA does it matter whether you have insurance or would everyone be given a CT scan after banging their head? Do celebrity actresses get treated differently than single mothers earning $35,000 per year with no health insurance?

And what does Hussein have to do with medical care in Canada?

---

[Hat Tip: Pure Pedantry]

Old Tools

 
Eva has posted some photos of old lab equipment and tools [Old Tools]. Check them out to see if you recognize anything.

Here's another contribution. This one is pretty easy but starting tomorrow they're going to get much harder. (Click to embiggen.)

---

Signals of Positive Selection in Humans?

Signals of recent positive selection in a worldwide sample of human populations is the title of a paper that has just been published in Genome Research (Pickrell et al. 2009).

These workers looked for signs of positive selection using techniques similar to those employed by Hawks et al. in their 2007 paper. That 2007 paper serves as one of the important bits of evidence in the recently published book, The 10,000 Year Explosion.

The idea is to pick out regions of the genome that have linked clusters of polymorphisms (SNPs = single nucleotide polymorphisms). These cluster are called haplotypes and they indicate that a region of the genome has not undergone much recombination in the recent past, because recombination tends to shuffle polymorphisms. One way this linkage could be preserved is when a part of the genome is under positive selection so its increase in frequency is rapid. This is called a selective sweep.

Pickrell et al. (2009) examined a database of 657,143 SNPs called the Human Genome Diversity-CEPH Panel (HGDP). These polymorphisms come from a global sample of 53 populations. The Hawks et al. (2007) paper examined the HapMap database of 3.1 million SNPs from three populations.

Pickrell et al. (2009) also detect a large number of regions that are candidates for positive selection. Their sites overlap those of the earlier study—about half of their sites were also identified by Hawks et al. (2007).

A number of candidates for positive selection are discussed in the paper but the authors note that many of the potential sites are not near any genes that have been well-characterized. It's important to look at individual cases in order to get a feel for the data, especially since the possibility of false positives is a concern.

Specific Examples

Here are a few of the single genes that were identified in one or more groups (e.g. Bantu, Europeans, native American etc.) They are from the top ten strongest signals so they presumably represent some of the best cases for selection.

Heat Shock Transcription Factor 2 (HSF2): This is one of two genes for the major heat shock transcription factor. The heat shock genes are highly conserved and so is their regulation. It's very unlikely that a mutation in the native North American population would be beneficial relative to the allele in all other populations.

succinate-CoA ligase, GDP-forming, β-subunit (SUCLG2) This is the gene for succinyl-CoA synthetase, one of the enzymes of the Krebbs cycle. The data suggest that an allele of this gene was positively selected in the population of Oceania (Pacific Ocean). This doesn't seem very likely.

oxoacyl-ACP synthase, mitochondrial (OXSM) This is the mitochondrial version of a β-ketoacyl synthetase, a standard enzyme required for fatty acid synthesis. An allele shows signs of positive selection in Eurasian populations but not in any other population. It doesn't seem likely that there's an allele conferring a beneficial effect that hasn't already become fixed in mammals over 100 million years ago.

mannosidase, alpha, class 2A, member 1 (MAN2A1) This is a mannosidase located in the Golgi. It's required for one of the last stages in the oligosaccharide maturation pathway—a pathway that's found in all eukaryotes. Pickrell et al. (2009) suggest that an allele of this gene has been selected in the pygmy and Bantu populations. Again, it isn't likely that a standard metabolic gene would be selected in this way.

False Positives?

The patterns of potential selective sweeps strongly suggest local and/or regional sweeps. Since this is the pattern you might expect from random genetic drift, it raises a question about false positives. The authors of the 2009 paper say, ...

Further exploration of the geographic patterns in these data and their implications is warranted, but from the point of view of identifying candidate loci for functional verification, the fact that putatively selected loci often conform to the geographic patterns characteristic of neutral loci is somewhat worrying. This suggests that distinguishing true cases of selection from the tails of the neutral distribution may be more difficult than sometimes assumed, and raises the possibility that many loci identified as being under selection in genome scans of this kind may be false positives. Reports of ubiquitous strong (s = 1-5%) positive selection in the human genome (Hawks et al. 2007) may be considerably overstated. [My emphasis-LAM]

It should come as no surprise that John Hawks disagrees. He has posted a rebuttal on his blog at: Overstating the obvious.

It's an interesting debate but let's not lose sight of the most important point—it is a scientific debate. The case for massive amounts of accelerated human evolution has not been proven in spite of what you might read in The 10,000 Year Explosion and in articles in the popular press.

UPDATE: See Razib's posting: Signals of recent positive selection in a worldwide sample of human populations...maybe

---

Hawks, J., Wang, E.T., Cochran, G.M., Harpending, H.C., and Moyzis, R.K. (2007) Recent acceleration of human adaptive evolution. Proc. Natl. Acad. Sci. (USA) 104:20753-20758. Epub 2007 [PubMed] [DOI:10.1073/pnas.0707650104]

Pickrell, J.K., Coop, G., Novembre, J., Kudaravalli, S., Li, J.Z., Absher, D., Srinivasan, B.S., Barsh, G.S., Myers, R.M., Feldman, M.W., and Pritchard, J.K. (2009) Signals of recent positive selection in a worldwide sample of human populations. Genome Research 23 published in advance March 23, 2009 [DOI: 10.1101/gr.087577.108]