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Tuesday, August 21, 2007

Identity of the Product of Mendel's Green Cotyledon Gene

 
This posting has been replaced by Identity of the Product of Mendel's Green Cotyledon Gene (Update).


Another of Mendel's seven genes has been identified. This one is described in his 1865 paper Experiments in Plant Hybridization [MendelWeb] as character number 2.
2. To the difference in the color of the seed albumen (endosperm). The albumen of the ripe seeds is either pale yellow, bright yellow and orange colored, or it possesses a more or less intense green tint. This difference of color is easily seen in the seeds as their coats are transparent.
Mendel's reference to the color of albumin, or endosperm, is inaccurate. He was actually observing the color of the cotyledons—the "seed leaves" that surround the embryo in the pea seed. These tiny leaves are covered by a seed coat that is partially transparent.

In wild-type peas the seeds turn yellow as they mature (i) but certain mutants exhibit a "stay-green" phenotype where the peas retain their green color (I). The figure shows seeds from a plant with the II genotype (top) and the ii genotype (bottom). The seed coat has been removed from the lower pair of each group of four peas.

In a paper just published in the Proceedings of the National Academy of Sciences (USA) a group in Japan has identified the "stay green" gene that Mendel worked with (Sato et al., 2007). It turns out that the gene, called SGR (stay-green), encodes an enzyme that is localized to chloroplasts and plays a role in the degradation of chlorophyll during senescence and maturation of seeds. When the enzyme is defective chlorophyll isn't broken down and the tissue stays green.

This brings to three the number of Mendel's genes that have a known function. The wrinkled pea phenotype is caused by a defect in the gene for starch branching enzyme (Bhattacharya et al., 1990) [Biochemist Gregor Mendel Studied Starch Synthesis]. The tall/short phenotypes are caused by defects in the gene for gibberellin 3β-hydroxylase (Martin et al., 1997). Gibberellins are plant growth hormones.

[Photo Credit: The photograph of mutant and wild-type pea seeds is taken from Figure 1 of Sato et al. (2007)]

Bhattacharyya, M. K., Smith, A. M., Ellis, T. H., Hedley, C., and Martin, C. (1990) The wrinkled-seed character of a pea described by Mendel is caused by a transposon-like insertion in a gene encoding starch-branching enzyme. Cell 60:115-122.

Martin D.N., Proebsting W.M., Hedden P. (1997) Mendel's dwarfing gene: cDNAs from the Le alleles and function of the expressed proteins. Proc. Natl. Acad. Sci. (USA) 94:8907–8911.

Sato Y., Morita R., Nishimura M., Yamaguchi H., and Kusaba M. (2007) Mendel’s green cotyledon gene encodes a positive regulator of the chlorophyll-degrading pathway. Proc. Natl. Acad. Sci. (USA) (early publication, [August 20, 2007]).

Monday, August 20, 2007

Monday's Molecule #39

 
Today's molecule is complex but it has a very simple common name. The common name is not sufficient—you must supply the formal IUPAC name to win the prize. There's a direct connection between this Monday's Molecule and Wednesday's Nobel Laureate.

The reward (free lunch) goes to the person who correctly identifies the molecule and the Nobel Laureate(s). Previous free lunch winners are ineligible for one month from the time they first collected the prize. There's only one (Marc) ineligible candidate for this Wednesday's reward since many recent winners haven't collected their prize. The prize is a free lunch at the Faculty Club.

In preparation for the beginning of classes in three weeks I'm going to start requesting email responses. 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 the Nobel Laureate. All responses will be posted tomorrow along with the time that their message was received on my server. This way I may select multiple winners if several people get it right.

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

Sunday, August 19, 2007

Like a Broken Record ...

 
Matt Nisbet is at it again. His particular spin frame on the rationalism vs. superstition debate is that the rationalists are making too much noise. According to Nisbet, we atheists are hurting the "cause" (what cause?) by speaking out loudly against superstition in the form of religion. Apparently it would be better to tone down the rhetoric in order to avoid offending those who believe in superstition. This is the strategy that has been followed by Americans for the last 100 years or so. No matter how stupid the religious extremists are, whether from the pulpit or on talk radio, we mustn't say that they are stupid because that would hurt their feelings. Or rather, it would hurt the feelings of the moderate believers who tolerate and support the religious extremists.

Of course Matt doesn't recognize that this is just his personal opinion. Oh no, that wouldn't be right, would it? If you are going to attack Dawkins, Hitchins, and Harris then you'd better frame it make it sound like an attack based on solid scientific reasoning. Here's what Matt Nisbet says in his latest posting [Why the New Atheist Noise Machine Fails].
Everything we know from social science research on attitude formation and beliefs predicts that the communication strategy of the New Atheist noise machine will only further alienate moderately religious Americans, the very same publics who might otherwise agree with secularists on many social issues.
Everything we know from history predicts that social change is often stimulated and led by vocal "extremists" who dare to speak out even if it offends those who prefer the status quo. This was true of the women's movement, the civil rights movement, and the gay rights movement. In those cases it was the moderate male chauvinists, the moderate racists, and the moderate homophobes who were initially offended. They didn't like being told that their long-held beliefs were wrong. In all those cases I suspect there were Matt Nisbets who tried to silence the outspoken leaders because they were offending the average moderate citizen.

If social science "research" says that the cause of outspoken individuals always fails then that says a lot more about the so-called "research" of social scientists than it does about reality.
The Dawkins/Hitchens PR campaign provides emotional sustenance and talking points for many atheists, but when it comes to selling the public on either non-belief or science, the campaign is likely to boomerang in disastrous ways.
The experiment is under way. Up until 2005, atheism was pretty much hidden under a bushel and religious superstition was rarely confronted in public. The result is that America is the most religious country in the industrialized world and evolution isn't taught in schools. Let's see if there's any change in the status quo over the next decade as the Dawkins/Hitchens framing PR campaign continues. According the Nisbet, the country will become even more religious because of the backlash. I'm betting that religion will become less important to Americans when they realize that there are other options.

There are times when I wonder which side Nisbet is on. It sounds to me like he's perfectly happy with the way things have been for the past several decades.

Don't Mess with Canadians

 
I recently returned from spending a week in a foreign country. I did not behave like the Canadian in this video although there were times ...



[Hat Tip: Canadian Cynic]

Friday, August 17, 2007

The Cause of Variation in a Population

John Dennehy of The Evilutionary Biologist has posted a wonderful article on This Week's Citation Classic. The classics are two back-to-back papers on genetic variation in fruit flies (Hubby and Lewontin (1966), Lewontin and Hubby (1966)). That's Lewontin on the left.

Please get on over to The Evilutionary Biologist and read what John has to say. These were very important and groundbreaking papers when they came out and everyone needs to know why.

Here's some background.

In the olden days there were two competing theories to explain variation (heterozygosity) in a population. The classical theory said that mutations are constantly being removed from the population by positive natural selection or purifying selection. Variation is a transient phenomenon that would disappear entirely if it weren’t for new mutations that arise at a significant rate.

The balance theory maintains that variation in a population is often due to balancing selection. The best known example of balancing selection is the allele for sickle cell disease. In the heterozygous state it confers resistance to malaria but in the homozygous state it is often lethal. Both the sickle cell allele and the wild type allele are maintained in the human population by balancing selection.

Hubby and Lewontin (1966) discovered that there was a huge amount of genetic variation in fruit flies. Their data suggested that 50% of all loci had multiple alleles. This is difficult to reconcile with the balance theory and it was also a big surprise to those who supported the classic theory. It seemed unlikely that at any given point in the evolutionary history of a species that so many genes could be undergoing selection. Further work confirmed that other species contained a huge amount of variation.

The solution to this surprising observation was the recognition that most of the alleles were neutral. The variation is explained by fact that fixation by random genetic drift is much slower than fixation by natural selection. Thus, while the variation is transient in the sense that it is a snapshot of an ongoing process, the process is not selection but drift.

The results of Hubby and Lewontin (1966) led directly to Neutral Theory.
The neutral theory also asserts that most intraspecific variability at the molecular level (including DNA and protein polymorphisms) is selectively neutral, and is maintained in the species by the balance between mutational input and random extinction. In other words, the neutral theory regards protein and DNA polymorphisms as a transient phase of molecular evolution and rejects the notion that the majority of such polymorphisms are adaptive and actively maintained in the species by some form of balancing selection.
                M. Kimura
This explanation is also known as the Neoclassical Theory. Balancing selection is now thought to play only a minor and insignificant role in the cause of variation in a population.
... the neoclassical theory is not refuted by occasional observations of overdominance for fitness, because the theory does not deny that cases exist but only that they are common and explain a significant proportion of natural variation. So it is no use trotting out that tired old Bucephalus, sickle-cell anemia, as a proof that single-locus heterosis can exist. Anyone who has taught genetics for a number of years is tired of sickle-cell anemia and embarrassed by the fact that it is the only authenticated case of overdominace available. “If balancing selection is so common," the neoclassicists say, "why do you always end up talking about sickle-cell anemia?"
                R. Lewontin

[Photo credit: The photograph of Richard Lewontin is from (Photographs of Participants in the Molecular Evolution Workshop)]

Wednesday, August 15, 2007

Where's the Evidence for Intelligent Design Creationism?

 
Denyse O'Leary has friend named David Warren. Warren writes articles for newspapers and he and Denyse are friends because they both worship at the church of anti-Darwinism. Over on Post-Darwinist Denyse brags about the latest article written by her friend [ Another Toronto journalist takes swat at Darwinists (or Darwinoids)]. Note the title of the blog article. It's more of the same old, same old, "Darwinist" baiting. Turns out that 99.9% of the IDiot movement is about attacking evolution (their version) and 0.1% is about presenting evidence for intelligent design. (And even that tiny amount of evidence has been refuted or shown to be irrelevant.)

So what about David Warren? Is he any different—don't hold your breath. Here's the article that he wrote for some Canadian newspapers [Panspermianism]. The main point of the article is supposed to be that panspermia is ruled out because scientists have shown that DNA won't survive in outer space (*yawn*). But the real purpose of the article is to whine about the evil atheist materialists and how they are suppressing the IDiots.
Much of the “star chamber” atmosphere, that has accompanied the public invigilation of microbiologists such as Michael J. Behe, and other very qualified scientists working on questions of design in organisms and natural systems, can only be explained in this way. The establishment wants such research to be stopped, because it challenges the received religious order, of atheist materialism. Any attempt, or suspected attempt, to acknowledge God in scientific proceedings, must be exposed and punished to the limit of the law; or by other ruthless means where the law does not suffice.
There's more, but you get the idea. The IDiot movement is scientifically bankrupt. They have no scientific evidence to back them up so the only thing they can do is lash out at their opponents. When is the last time you've seen an article from an IDiot that explains any evidence for the existence of an Intelligent Designer? That's right, hardly ever. Is there a reason why they don't support their case with real data? Yep, you bet there is. And that's exactly why they have to stoop to attacking "Darwinism" at every chance they get. They don't have any other option. Pathetic, isn't it?

[Image credit: The photograph is from one of my students, Zarna. That's her in the picture. She took it last December in India (Oh My God)]

Should Cloning Humans Be Legal?

 
In the July 21 issue of New Scientist, Hugh McLachlan thinks that we should legalize cloning of humans [Let's legalise cloning].
But why are we so against the idea of cloned human babies? As a bioethicist specialising in reproductive issues, I believe it has more to do with an irrational fear of cloning than any logical reason. All the arguments in favour of a ban describe risks that we accept quite easily and naturally in other areas of reproduction.

One argument against human cloning is the idea that it is morally wrong or undesirable to create replicas of people. But although a clone has the same gene set as the adult from which it was cloned, environmental factors will ensure that the resulting individual is not an identical copy, either psychologically or physically. What's more, we accept genetically identical people in the form of twins. If anything, clones would be less alike than twins because they would be different ages and be brought up in different contexts. Objecting to cloning on these grounds makes no sense.
I agree with McLachlan. Aside from the safety issue, there doesn't seem to be any good reason to forbid the cloning of humans.

This is a topic that's frequently discussed in "ethics" classes. I've never really understood what "ethics" actually means—but I'm working on it. The cloning of humans isn't an ethical issue for me personally because there isn't a conflict between two versions of what I think I ought to do. However, maybe it's an ethical issue for society as a whole because there are some people who think that it is unethical to clone people. Is that right? What's unethical about it?

Do we define "ethical" issues in terms of conflict between different groups? If so, is there a way of distinguishing between issues where the two sides are almost equally represented and those where one side has an overwhelming majority? For example, is the cloning of humans still an ethical issue in a society where 99% of the population is opposed? Does it cease to be an ethical issue if 99% are persuaded to accept human cloning?

Tuesday, August 14, 2007

Amazing Grace

 
Last night we saw a screening of the film Amazing Grace in a small cozy theater. At the end of the movie there was a fascinating talk by one of the producers Ken Wales. We learned a lot about how the film was made.

The film follows the efforts of William Wilberforce to abolish slavery in the British Empire at the end of the eighteenth century. Wilberforce and his close friend William Pitt the Younger, who became Prime Minister in 1783, finally succeeded in eliminating slavery by 1807.

There's mention of the fact that Wilberforce was a Christian and some of his allies were preachers but this isn't an important theme. The movie makes it clear that Pitt, who was a prime mover in social change, did not share Wilberforce's beliefs. During the discussion afterward it was clear that the religious motivation was important to some people.

The title of the movie comes from the song Amazing Grace whose words were composed by John Newton, an ex-slave trader who converted to Christianity. Newton, who has a significant part in the movie, influenced Wilberforce and served as his mentor.

One interesting scene depicts a debate in the House of Commons in 1778. The newly elected Wilberforce is advocating the withdrawal of British forces from America, thus abandoning the attempt to put down the rebellion. Wilberforce is attacked and challenged to distinguish between appeasement and surrender. "It's merely a question of timing," he says.

This scene, and many others, reveal that Great Britain was a functioning democracy at the time of the American Revolution. It contrasts markedly with the general impression of Americans who tend to think that this sort of representative democracy was invented by them in 1776.

William Wilberforce's third son was Samuel Wilberforce ("Soapy Sam") who became the Bishop of Oxford and debated evolution with Thomas Huxley in 1860.

Tangled Bank #86

 

The 86th issue of the Tangled Bank has been posted on Fish Feet [Tangled Bank #86].

Monday, August 13, 2007

Peter Lawrence on What's Wrong with Science

 
Peter Lawrence is a Professor at the University of Cambridge in Cambridge, UK. He has worked on various aspects of fruit fly development for almost 40 years. Readers may know him as one of the authors of Wolpert's Principles of Development or as the author of The Making of a Fly.

Peter is a very smart guy. He thinks a lot about the "big picture" and not just the minutiae of day-to-day work in a competitive environment. That's why his article in this month's issue of Current Biology is worth reading. Lawrence writes about what's wrong with modern science [The Mismeasure of Science].

For most scientists, there won't be any revelations in the article but it's put together well and covers all the bases. The main point is that today's scientists have to worry far too much about "productivity" in order to get funded. The system is geared towards artificial measurements of research success that may, or may not, reward creativity and innovation.

Modern science, particularly biomedicine, is being damaged by attempts to measure the quantity and quality of research. Scientists are ranked according to these measures, a ranking that impacts on funding of grants, competition for posts and promotion. The measures seemed, at first rather harmless, but, like cuckoos in a nest, they have grown into monsters that threaten science itself. Already, they have produced an “audit society” [2] in which scientists aim, and indeed are forced, to put meeting the measures above trying to understand nature and disease.

The journals are evaluated according to impact factors, and scientists and departments assessed according to the impact factors of the journals they publish in. Consequently, over the last twenty years a scientist's primary aim has been downgraded from doing science to producing papers and contriving to get them into the “best” journals they can [3]. Now there is a new trend: the idea is to rank scientists by the numbers of citations their papers receive. Consequently, I predict that citation-fishing and citation-bartering will become major pursuits.
You need to read the full article to get all the details.

So, what can we do about it? It's an old complaint, one that's been openly discussed even since I first met Peter Lawrence back in the mid-1970's. If a bunch of (relatively) smart scientists can't figure out how to fix the problem then maybe it's unfixable.

Here's where I think Lawrence drops the ball. He proposes the same tired old "remedies" that we've never adopted in the past in spite of the fact that we all pay lip service to their benefits. He wants us all to pay attention to "quality" and "originality" over quantity. He wants us to be more careful about putting authors names on a paper. He wants a code of ethics for scientists. He wants to reform the peer review process in the leading journals. None of this is going to happen as long as money is tight and the granting agencies have to come up with defensible policies for turning down 75% of grant applications.

The short term solution is to put more money into the grant system and to stop hiring more scientists. The long term solution is to look for better ways of funding. I like the idea of giving large block grants to departments and letting the researchers divide it up as they see fit. This would have worked well in any department I've been in but I hear horror stories about other departments.


[Photo Credit: The photograph of Peter Lawrence is from his website at the University of Cambridge (Peter A. Lawrence]
Lawrence, P.A. (2007) The mismeasurement of science. Current Biology 17:R583-R585.

Half-Truths in Sicko?

 
Jim Giles reviewed Michael Moore's Sicko in the July 14th issue of New Scientist [Review: Sicko, directed by Michael Moore]. Like many reviews, this one conceded that Moore has a point about the shape of health care in the USA but was reluctant to admit that other countries are doing better. One paragraph mentioned "half-truths."
For the most part, Moore makes his case by absenting himself from the screen and allowing those who have been let down by the system to do the talking. Then he travels to the UK and France and finds that what conservatives in the US damn as "socialised medicine" actually works well. He does the same in Cuba, ferrying ill Americans to the island where they receive excellent healthcare at almost no cost. The result is a moving, funny and shocking film. It is a powerful call for change, despite its half-truths.
In last week's issue of New Scientist, a letter writer challenged Giles to produce his "half-truths," pointing out that the Sicko website documents every claim in the movie.

Here's how Jim Giles responded ...
The most obvious half-truths were the slanted depictions of the healthcare systems in the UK, France, and Cuba. The British NHS can be great, but waiting lists are often long and access to certain drugs can depend on where a patient lives. France's system is indeed highly rated, but Moore did not mention the very high taxes there. Cuba's public health is far above what would be expected for a country with limited resources and suffering the consequences of the US trade embargo, but it also restricts access to certain drugs and technologies.
Some of these sound very much like half-truths to me. Yes, waiting lists for non-lifethreatening procedures are often longer in countries with socialized medicine. That is, they are longer than the wait for similar procedures in a fully private system where people can afford to pay for it. On the other hand, the waiting time in the UK is a lot shorter than it is for Americans who can't afford decent health insurance, isn't it?

Access to certain drugs is restricted in all socialized medicine systems. For example, the system won't pay for drugs that don't work and haven't been approved. This is bad news for quacks who generally do much better under a private system. Socialized medicine often won't pay for expensive drugs if a cheaper alternative is available. Is this what Giles meant?

It's true that taxes are higher in countries that provide universal access to medical treatments. This isn't a half-truth in Sicko. As I recall, it's one of the main points. The US system is more expensive in spite of the fact that it's run by the private sector.

Sunday, August 12, 2007

Gene Genie #13

 




Gene Genie #13 has been posted on The Genetic Geneologist [Gene Genie #13: Into the Future].

The Hominid Bush

 
Brian Switek of Laelaps has posted a wonderful essay on Homo sapiens: The Evolution of What We Think About Who We Are. Read it.

In a just world, the IDiots like Jonathan Wells would read what Brian, and others, have to say and stop spreading lies about what scientists think.

[Photo Credit: The photograph of Hamlet is from The Young Shakespeare Workshop]

Jim Watson on the Discovery of the Double Helix

 
THEME
Deoxyribonucleic acid (DNA)
This is a nice addition to my earlier postings on the story of DNA [The Story of DNA (Part 1)][The Story of DNA (Part 2)]. This story (below) is straight from the horse's mouth.



[Hat Tip:Shalini].

University of Toronto Professor in Space

 
That's astronaut Dave Williams on the right. He's a University of Toronto adjunct professor of surgery. According the the University of Toronto press release,Williams was a Professor here in emergency medicine until he was selected for the astronaut training program in 1992 [U of T professor to walk in space].