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Thursday, December 18, 2008

Speciation in Monkeyflowers

 
Within a species there may be distinctive subspecies that have different allele frequencies. The differences are maintained because there is restricted gene (allele) flow between them. The two subspecies may look very different or they may be very similar in appearance.

Genetic exchange between the subspecies is often prevented because the subspecies are geographically separated. This is the first step on the path to allopatric speciation. But genetic exchange can also be restricted by other mechanisms, for example the timing of reproduction, that occurs even if the subspecies inhabit the same environment. This could lead to sympatric speciation.

In either case, the two subspecies will become distinct species—as defined by the biological species concept—when it becomes impossible to form hybrids due to genetic incompatibility. The study of actual speciation events is a hot topic in evolution these days. One of the goals is to identify the genes responsible for preventing the formation of fertile hybrids. The other goal is to identify the mechanism by which the alleles of these genes become fixed in the subspecies. Is it by natural selection or random genetic drift? (Shuker et al. 2005)

One of the best studied examples of speciation in action is due to the work of H.D. Bradshaw and Douglas Schemske at the University of Washington in Seattle, Washington (USA) (Schemske is now at Michigan State University). They studied two species of monkeyflowers that grow near streams and rivers in the mountains and valleys of western North America.

Mimulus lewisii (top) is found primarily at higher elevations (1600 m to 3000 m) while Mimulus cardinalis (right) grows at lower elevations (sea level to 2000 m). Their ranges overlap at moderate elevations in the mountains of California but hybrids are exceedingly rare.

The species differ in a number of characteristics including leaf shape and stem height but the most obvious differences are in the flowers. Mimulus lewsii has pink flowers that are quite open. They attract bumblebees and in the wild 100% of pollinations within this subspecies are by bees. Mimulus cardinalis has red flowers with a more narrow shape. These flowers attract hummingbirds who are responsible for 98% of pollination events in M. cardinalis.

When crossed in a greenhouse, the two species produce fertile hybrids so technically they are not really species but subspecies.

Ramsey et al. (2003) have studied the barriers to gene flow in the wild. Much of it is due to ecogeographic isolation, which is a fancy way of saying that the species don't often come in contact. They grow at different elevations and each species has become adapted to that elevation so that M. lewisii, for example, does not survive well at low elevations and M. cardinalis can't take the cold and the shorter growing season at high elevations.

The fact that the two species have different pollinators is a major factor in preventing gene flow between them. Hummingbirds hardly ever visit M. lewisii and in the overlapping zones there were very few recorded instances of bees visiting flowers from both species. Thus, the opportunities for cross-pollination were effectively zero. What this means is that, "even in sympatry these species are isolated to a large degree by pollinators" (Ramsey et al. 2003).

There are other factors contributing to genetic isolation. The hybrid plants are somewhat less fit and cross-pollination results in fewer seeds than pollination within a (sub)species. The sum of all these factors means that, in the wild, the total reproductive isolation between the two species is 0.9974 to 0.9998. In other words, they don't mix! (But recall that they can readily form fertile hybrids when crossed in the greenhouse.)

In this example, a major component of the restricted gene flow is due to physical separation of the species and that separation is the result of adaptation to different environments. In that sense, the path to speciation is driven, in part, by natural selection. The species are not genetically incompatible so we're not dealing with mutations that prevent hybridization as would be the case if they were true biological species.

Attention has focused on flower color and shape since that determines whether an individual is pollinated by bumblebees or hummingbirds. It's another step toward preventing gene flow between the species. Is it due primarily to selection or drift?

Schemske and Bradshaw (1999) identified a locus, called yellow upper (YUP), that plays a large role in determining flower color in the two species. The locus affects carotenoid distribution in the petals. In M. cardinalis carotenoids are found throughout the petals and the flowers are red. Bees are not attracted to red flowers. The YUP allele in M. lewisii results in less carotenoid and the flowers are pink. These flowers attract bees.

A subsequent study by Bradshaw and Schemske (2003) established that the YUP alleles are directly responsible for much of the pollinator discrimination observed in monkeyflowers. In the second study the authors created near-isogenic lines (NIL) that differed only at the YUP locus.

The normal M. lewisii flower is pink and the petals are in an open shape (a). The normal M. cardinalis flower is red and the shape of the flower is quite different (c). The dominant YUP allele from M. lewisii prevents carotenoid deposition and when it is bred into M. cardialis the flowers are pink (d). The recessive yup allele from M. cardinalis causes more carotenoid to be deposited making the flowers orange in an M. lewisii background (b).

The plants were tested in a natural environment where the ranges of the two species overlapped and both bees and humingbirds were common. Bees preferred the pink flowers whether they were in an M. lewisii background or an M. cardialis background. Conversely, hummingbirds preferred the orange and red flowers in both backgrounds. Thus, the two species have adapted to different pollinators and a large part of this adaptation is due to flower color.

Here's where it gets tricky. Is the switch from bee pollination to hummingbird pollination driven by natural selection? In other words, when the mutation causing red flowers first arose did it confer a fitness advantage on the individuals that came to be pollinated by hummingbirds?

Here's how Bradshaw and Schemske (2003) address this question,
As ‘mutations’ at the YUP locus decrease visitation by the current pollinator guild, and simultaneously increase visitation by a new pollinator guild, are there plausible ecological circumstances in which the mutant might be favoured by natural selection? The combined rate of bumblebee and hummingbird visitation to the yellow-orange-flowered ‘mutants’ of M. lewisii is just 26% of that to the wild-type pink flowers, and the combined rate for dark-pinkflowered ‘mutants’ of M. cardinalis is 95% of the wild type. This implies that a change in the relative abundance of bumblebees and hummingbirds, compared with the pollinator assemblage present during our field experiments, would be required for the mutant to be favoured by natural selection in the common ancestor of M. lewisii and M. cardinalis. The change in relative abundance of pollinators necessary to produce equal visitation to both flower colour phenotypes can be estimated from our data. A ninefold decrease in the relative abundance of bumblebees would produce equal combined visitation rates in the wild-type pink-flowered and ‘mutant’ yellow-orange-flowered M. lewisii NILs. At the equilibrium point, 99% of visitors to wild-type M. lewisii flowers would be bumblebees, whereas 87% of visitors to ‘mutants’ would be hummingbirds. In the M. cardinalis NILs, a twofold increase in the relative abundance of bumblebees would produce equal visitation rates to pink and red flowers. At the equilibrium point, hummingbirds would be virtually the only visitor to the wild-type red M. cardinalis flowers, and remain the major visitor (89% of visits) even to the dark-pink ‘mutants.’
In order for the red flower allele to be fixed by natural selection there would have to be a significant decline in the bee population at the time the mutation arose. Presumably, this decline would have only occurred in a small part of the range leading to a subpopulation with red flowers while the main, wild-type, population (pink flowers) continued to be visited by bees.

The authors don't mention the other possibility; namely, that the red flower allele (yup) spread in a subpopulation by random genetic drift. In this scenario, there is no selective advantage to individual plants if they are pollinated by humingbirds. Clearly the evolution of pollinator discrimination by flower color will lead to restricted gene flow between the two species but it is not clear whether this epiphenomenon is due to selection for hummingbird pollination or random genetic drift.


[Photo Credits: Mimulus lewisii or Purple monkey-flower (top) is from flickr. Mimulus cardinalis or Cardinal monkeyflower (second from top) is from the Arizona-Sonore Desert Museum.


Bradshaw, H.D. Jr. and Schemske, D.W. (1999) Allele substitution at a flower colour locus produces a pollinator shift in monkeyflowers. Nature 426:176-178. [doi:10.1038/nature02106] [PDF]

Ramsey, J., Bradshaw, H.D. Jr., Schemske, D.W. (2003) Components of Reproductive Isolation between the Monkeyflowers Mimulus lewisii and M. cardinali (Phrymaceae). Evolution 57:1520-1534. [PDF]

Schemske, D.W. and Bradshaw, H.D. Jr. (2003) Pollinator preference and the evolution of floral traits in monkeyflowers (Mimulus). Proc. Natl. Acad. Sci. (USA) 96:11910-11915. PDF]

Shuker, D.M., Underwood, K., King, T.M., and Butlin, R.K. (2005) Patterns of male sterility in a grasshopper hybrid zone imply accumulation of hybrid incompatibilities without selection. Proc. Biol. Sci. 272:2491-2497. [DOI: 10.1098/rspb.2005.3242]

Is Bill O’Reilly Really this Stupid?

 
Don't answer that. It's a rhetorical question.

Honestly, I just don't understand how someone who's a prominent television personality can be so totally ignorant of the very issue that he rants about. It's not rocket science. The law isn't that hard to understand.

Maybe there's something about being religious that clouds the mind?

Listen for the following words from attorney Megan Kelley, "I've never met a non-lawyer who argues the law so confidently, albeit, so wrongly."




[Hat Tip: Friendly Atheist: You Are Wrong! You Are *So* Wrong!]

Wednesday, December 17, 2008

Get a Job

 
Canada Research Chair (Tier I)
in Comparative Genomics and Evolutionary Bioinformatics
at Dalhousie University, Halifax, Canada

The Faculty of Medicine at Dalhousie University is seeking to attract an outstanding individual eligible for nomination for a Tier I Canada Research Chair faculty position in the area of comparative genomics and evolutionary bioinformatics. The successful candidate will be recognized internationally as a leader in this research area and will join the newly formed Centre for Comparative Genomics and Evolutionary Bioinformatics (http://cgeb.dal.ca/), an interdisciplinary research group with diverse and complementary interests in molecular evolution, microbial diversity, protistology, phylogenetics, genomics, proteomics and bioinformatics. Dalhousie is a leading Canadian research-oriented University, located in Halifax on the scenic Atlantic coast of Nova Scotia.

The Canada Research Chairs program was established by the Government of Canada to foster world class centres of research excellence in a global, knowledge-based economy (www.chairs.gc.ca). Applicants should have a Ph.D. in Biochemistry/Molecular Biology or a related discipline, and currently hold the rank of Professor or Associate Professor (with expectation of promotion to Professor within 1-2 years). The successful candidate will be offered a tenured or tenure-track appointment in the Department of Biochemistry & Molecular Biology (www.biochem.dal.ca/) with limited teaching responsibilities. Preference will be given to applicants with interdisciplinary expertise in both laboratory-based biochemical/molecular biological approaches as well as bioinformatics and/or computer science.

To apply send a curriculum vitae, a brief outline of research achievements and goals, and arrange for three letters of reference to be sent, under separate cover, to: Dr. David M. Byers (Chair, Search Committee), Department of Biochemistry & Molecular Biology, Dalhousie University, Sir Charles Tupper Medical Building, 5850 College Street, Halifax, NS, B3H 1X5 Canada. Interviews may commence as early as January 15th, however we will continue to receive applications until a successful candidate has been chosen up to March 1, 2009. All Chairs are subject to review and final approval by the CRC Secretariat.

Dalhousie University is an Employment Equity/Affirmative Action employer. The University encourages applications from qualified Aboriginal people, persons with a disability, racially visible persons and women.


Get a Job

 
Assistant Professor, Tenure Stream
in Cellular and Molecular Biology of Lipids
Department of Pediatrics, Atlantic Research Centre
Dalhousie University
Halifax, Nova Scotia, Canada


The Department of Pediatrics at Dalhousie University invites applications for a probationary tenure-track position at the rank of Assistant Professor. Candidates should have demonstrated potential to develop a nationally and internationally recognized research program in the field of lipid metabolism, signaling or transport, with emphasis on human diseases such as cancer, obesity, diabetes or cardiovascular. The successful candidate will join an established, interactive group of investigators with complementary research interests at the Atlantic Research Centre (ARC). Members of the ARC have ready access to established core research facilities that include: tissue culture and animal care, cellular imaging (confocal and electron microscopy, flow cytometry), mass spectrometry and microarray technology.

Applicants must hold a PhD degree or equivalent and have at least three years post-doctoral training in biomedical sciences. The successful applicant will be expected to compete for external research and salary support, supervise graduate students and contribute to the teaching activities of the Department. Salary will be commensurate with qualifications and experience. Further information concerning this position, the Department and the ARC may be obtained by consulting arc.medicine.dal.ca and associated links.

Dalhousie University is a research-intensive institution located in the historic port city of Halifax, Nova Scotia, which boasts excellent recreational, cultural and lifestyle opportunities (www.halifax.ca/visitors.asp).

Interested applicants should submit a CV as well as send a statement outlining their research and teaching interests. They should have three letters of reference sent under separate cover directly to the Chair of the Search Committee. At least 2 of these references must come from academic referees.

Chair, Search Committee
Atlantic Research Centre
Room C302, CRC Building, 5849 University Avenue,
Dalhousie University
Halifax, Nova Scotia,
Canada B3H 4H7

Closing date for receipt of applications is January 31, 2009. Starting dates are negotiable; the positions may be filled by Sept. 1, 2009.

All qualified candidate are encouraged to apply; however, Canadians and permanent residents will be given priority. Dalhousie University is an Employment Equity/Affirmative Action employer. The University encourages applications from qualified Aboriginal people, persons with a disability, racially visible persons and women.


Get a Job

 
Department of Biochemistry
College of Medicine
University of Saskatchewan
Assistant Professor

The Department of Biochemistry invites applications for a tenure-track position at the level of Assistant Professor. Candidates must have a Ph.D. with at least 2 years of post-doctoral experience. The successful applicant is expected to establish a strong, independent and externally funded research program in biochemistry, preferably in a research area related to metabolism, gene expression, lipid and carbohydrate biochemistry or the biochemical basis of diseases. An interest and/or experience in bioinformatics would be an asset.

In addition, participation in teaching of both the undergraduate medical and biochemistry curricula will be required. The successful applicant will have a broad range of collaborative possibilities on campus with scientists in other departments and colleges, including the Canadian Light Source (www.cls.usask.ca/) and the Saskatchewan Structural Sciences Centre (www.usask.ca/sssc/).

Please submit both electronic and signed hard copies of the application, including curriculum vitae; a detailed statement on research interests and of previous teaching experience in a single PDF document to:

Dr. R.L. Khandelwal
Head, Department of Biochemistry, College of Medicine
University of Saskatchewan
107 Wiggins Road, Saskatoon, SK S7N 5E5 Canada.
E-mail: ramji.khandelwal@usask.ca
Phone:(306) 966-4368
Fax: (306) 966-4390

Applicants should also arrange for three confidential letters of reference to be sent separately to the same address.

The closing date for receipt of applications is February 1, 2009. The effective date for appointment is between April 1, 2009 and July 1, 2009.

All qualified candidates are encouraged to apply. However, Canadian citizens and permanent residents will be given priority. The University of Saskatchewan is committed to Employment Equity. Members of Designated Groups (women, Aboriginal people, people with disabilities and visible minorities) are encouraged to self-identify on their applications.


Nobel Laureate: Fred Sanger

 

The Nobel Prize in Chemistry 1980.

"for their contributions concerning the determination of base sequences in nucleic acids"



Frederick Sanger (1918 - ) was awarded the Nobel Prize for developing the chain termination, or dideoxy, method of sequencing DNA (The Sanger Method of DNA Sequencing). The method relies on synthesis of DNA in vitro using dideoxynucleotides that cause chain termination from time to time. The original method has been adapted to high throughput methods that are fully automated.

Fred Sanger shared the Nobel Prize with Walter Gilbert. It was Sanger's second Nobel Prize, his first was for developing methods to sequence proteins.


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.

[Photo Credit: The photograph show Fred Sanger in front of the Wellcome Trust Sanger Institute.]

Tuesday, December 16, 2008

Testing Natural Selection: Part 1

 
The latest issue of Scientific American has an interesting article by H. Allen Orr entitled Testing Natural Selection.
Biologists working with the most sophisticated genetic tools are demonstrating that natural selection plays a greater role in the evolution of genes than even most evolutionists had thought.
Orr is an adaptationist. His perspective on evolution focuses on natural selection as the predominant mechanism. He tends to dismiss all other mechanisms as either uninteresting or unimportant.

I though it might be interesting to compare what a pluralist might say about some of the things in the article. It's one way of highlighting the difference between the two points of view.

Naturally, as a pluralist, I disagree with some statements. My main beef, however, is with the growing tendency to over-emphasize natural selection as we approach the 200th anniversary of Darwin's birth and the 150th anniversary of publication of On the Origin of Species. I think it's possible to describe the differences between evolution in the eighteenth century and evolution in the 21st century without diminishing Darwin's contributions.

Orr begins his article by describing natural selection. He explains that there are several kinds of mutations ...
Most important, we know something about the effects of mutations on fitness. The overwhelming majority of mutations are harmful—that is, they reduce fitness; only a tiny minority are beneficial, increasing fitness.
That's not exactly how I would put it. I would have added that there's a third type of mutation that is neither harmful nor beneficial—neutral mutations.

Furthermore, I would have explained that the frequency of these three different kinds of mutations can vary considerably from one species to the next depending on the organization of the genome. In animals and plants, for example, most of the DNA does not seem to be essential so that the overwhelming majority of mutations are neutral and a smaller number—those that interfere with an essential function—are deleterious. A few mutations can be beneficial.

Orr goes on to say ....
Most mutations are bad for the same reason that most typos in computer code are bad: in finely tuned systems, random tweaks are far more likely to disrupt function than to improve it.
I would not use this analogy because it emphasizes something that I think is false; namely that organisms are "fine tuned systems." I tend to think of them as sloppy Rube Goldberg machines and not as well-tested computer code.

I would say that most mutations in essential regions of the genome are deleterious because random hits in DNA are more likely to make things worse than to make things better. The distinction is subtle, but important. Many adaptationists use language implying that living organisms are almost perfectly adapted to their present environment.

In the next section, Orr describes the advances of population genetics and its influence on how we understand natural selection. I would have described how population genetics led to an understanding of all type of evolution, and not just natural selection. Here's what Orr says,
Population geneticists have also provided insight into natural selection by describing it mathematically. For example, geneticists have shown that the fitter a given type is within a population, the more rapidly it will increase in frequency; indeed, one can calculate just how quickly the increase will occur. Population geneticists have also discovered the surprising fact that natural selection has unimaginably keen “eyes,” which can detect astonishingly small differences in fitness among genetic types. In a population of a million individuals, natural selection can operate on fitness differences as small as one part in a million.
I would have said that the growth of population genetics in the early part of the 20th century led to the recognition of random genetic drift as an important mechanism of evolution. Models were developed to explain how natural selection affected the increase in frequency of a beneficial allele and how neutral alleles could also increase in frequency even though they were invisible to natural selection.

The population geneticists also discovered that harmful alleles could become fixed by accident, although that turns out to be a rare event. More importantly, they discovered that natural selection has a stochastic component. Beneficial alleles will only become fixed part of the time. The probability depends on the fitness advantage. For example, if an allele has a fitness advantage of 10% then it will only become fixed 20% of the time. In 80% of cases when such an allele arises in a population it will be lost by random genetic drift before it becomes fixed.1

As the fitness advantage diminishes, the probability of fixation becomes lower and lower so that alleles with small fitness advantages (<1%) will hardly ever change the species. That's what population geneticists discovered about natural selection.

The probability of fixation of neutral alleles (or nearly neutral alleles) is very low but since there are so many more of them than beneficial alleles, much of evolution is characterized by changes due to random genetic drift.

The next section is "How Common Is Natural Selection?". This is where Orr asks the key question ...
One of the simplest questions biologists can ask about natural selection has, surprisingly, been one of the hardest to answer: To what degree is it responsible for changes in the overall genetic makeup of a population? No one seriously doubts that natural selection drives the evolution of most physical traits in living creatures—there is no other plausible way to explain such large-scale features as beaks, biceps and brains. But there has been serious doubt about the extent of the role of natural selection in guiding change at the molecular level. Just what proportion of all evolutionary change in DNA is driven, over millions of years, by natural selection—as opposed to some other process?
We've discussed this distinction between molecular changes and physical traits many times. One of the most annoying characteristics of adaptationists is that they insist on relegating other mechanisms of evolution to the level of DNA sequences but refuse to consider anything but natural selection when it comes to visible phenotypes. There is no justification for this assumption. Many physical traits can be neutral or even deleterious. They were not fixed by natural selection.2

What Orr says is simply not true. There are many biologists who seriously doubt that natural selection drives the evolution most physical traits, even though such pluralists readily agree that most adaptions are due to natural selection. Random genetic drift is a plausible way to explain many physical traits.
Until the 1960s biologists had assumed that the answer was “almost all,” but a group of population geneticists led by Japanese investigator Motoo Kimura sharply challenged that view. Kimura argued that molecular evolution is not usually driven by “positive” natural selection—in which the environment increases the frequency of a beneficial type that is initially rare. Rather, he said, nearly all the genetic mutations that persist or reach high frequencies in populations are selectively neutral—they have no appreciable effect on fitness one way or the other. (Of course, harmful mutations continue to appear at a high rate, but they can never reach high frequencies in a population and thus are evolutionary dead ends.) Since neutral mutations are essentially invisible in the present environment, such changes can slip silently through a population, substantially altering its genetic composition over time. The process is called random genetic drift; it is the heart of the neutral theory of molecular evolution.
As I've already pointed out, random genetic drift was discovered in the 1920s and it was incorporated into the first version of the Modern Synthesis in the 1940s. It dropped out of favor when the synthesis hardened at the time of the Darwin centennial in 1959.

Random genetic drift was revived in the late 1960's with the discovery of neutral alleles. Drift is the way in which selectively neutral alleles become fixed in a population. Random genetic drift and neutral theory are not synonyms.

As I indicated above, since the vast majority of animal and plant genomes is non-essential, it stands to reason that the vast majority of alleles will be neutral. Thus at the molecular level, at least, random genetic drift must be the dominant mechanism of evolution.

By the 1980s many evolutionary geneticists had accepted the neutral theory. But the data bearing on it were mostly indirect; more direct, critical tests were lacking. Two developments have helped fix that problem. First, population geneticists have devised simple statistical tests for distinguishing neutral changes in the genome from adaptive ones. Second, new technology has enabled entire genomes from many species to be sequenced, providing voluminous data on which these statistical tests can be applied. The new data suggest that the neutral theory underestimated the importance of natural selection.
Hmmm ... I could see where this was going even before I read it. Orr is about to quote the infamous work of Drosophila geneticists who have devised complicated tests to show that some synonymous mutations might confer a selective advantage in one species but not in another closely related species. Some of the papers claim that many alleles in coding regions are not neutral even thought they don't change the amino acid. There's no question that this is true in some cases.

It's also true that mutations altering the amino acid are sometimes beneficial, and therefore selected. However, if you align the amino acid sequences of a given gene from hundreds of species and map them on to the structure of the protein it becomes readily apparent that most substitutions cannot have a significant effect on the function of the protein. They must be neutral, or nearly neutral. As a matter of fact, in most proteins it is difficult to find any clearly beneficial alleles present in one species and not in the others.
In one study a team led by David J. Begun and Charles H. Langley, both at the University of California, Davis, compared the DNA sequences of two species of fruit fly in the genus Drosophila. They analyzed roughly 6,000 genes in each species, noting which genes had diverged since the two species had split off from a common ancestor. By applying a statistical test, they estimated that they could rule out neutral evolution in at least 19 percent of the 6,000 genes; in other words, natural selection drove the evolutionary divergence of a fifth of all genes studied. (Because the statistical test they employed was conservative, the actual proportion could be much larger.) The result does not suggest that neutral evolution is unimportant—after all, some of the remaining 81 percent of genes may have diverged by genetic drift. But it does prove that natural selection plays a bigger role in the divergence of species than most neutral theorists would have guessed. Similar studies have led most evolutionary geneticists to conclude that natural selection is a common driver of evolutionary change even in the sequences of nucleotides in DNA.
Pluralists disagree. We still think that random genetic drift is by far the dominant mechanism at the molecular level and that it even plays a significant role at the level of visible phenotypes.

In addition, we like to remind adaptationists that most beneficial alleles are eliminated by random genetic drift before they ever become fixed in a population.


1. Many biologists, and most evolutionary psychologists, do not understand this important point. They think that all they have to do is identify some (real or imagined) benefit and it will automatically take over the population no matter how small the benefit.

2. I know that Orr said "most" physical traits and not "all" physical traits. It's a distinction without meaning since the percentage of non-adaptive changes that adaptationists are willing to admit, grudgingly, is not much different than zero.

The Sanger Method of DNA Sequencing

 
In 1976 Frederick Sanger developed a method for sequencing DNA enzymatically using the Klenow fragment of E. coli DNA polymerase I. Sanger was awarded his second Nobel Prize for this achievement (he received his first Nobel Prize for developing a method for sequencing proteins). The advantage of using the Klenow fragment for this type of reaction is that the enzyme lacks the 5′ → 3′ exonuclease activity, which could degrade newly synthesized DNA. However, one of the disadvantages is that the Klenow fragment is not very processive and is easily inhibited by the presence of secondary structure in the single-stranded DNA template. This limitation can be overcome by adding SSB or analogous proteins, or more commonly, by using DNA polymerases from bacteria that grow at high temperatures. Such polymerases are active at 60° to 70°C, a temperature at which secondary structure in single-stranded DNA is unstable.

The Sanger sequencing method uses 2′,3′-dideoxynucleoside triphosphates (ddNTPs), which differ from the deoxyribonucleotide substrates of DNA synthesis by lacking a 3′-hydroxyl group (see below). The dideoxyribonucleotides, which can serve as substrates for DNA polymerase, are added to the 3′ end of the growing chain. Because these nucleotides lack a 3′-hydroxyl group, subsequent nucleotide additions cannot take place and incorporation of a dideoxynucleotide terminates the growth of the DNA chain. When a small amount of a particular dideoxyribonucleotide is included in a DNA synthesis reaction, it is occasionally incorporated in place of the corresponding dNTP, immediately terminating replication. The length of the resulting fragment of DNA identifies the position of the nucleotide that should have been incorporated.

Chemical structure of a 2′,3′-dideoxynucleoside triphosphate.
B represents any base.
DNA sequencing using ddNTP molecules involves several steps (as shown below). The DNA is prepared as single-stranded molecules and mixed with a short oligonucleotide complementary to the 3′ end of the DNA to be sequenced. This oligonucleotide acts as a primer for DNA synthesis catalyzed by DNA polymerase. The oligonucleotide-primed material is split into four separate reaction tubes. Each tube receives a small amount of an α[32P]-;abelled dNTP whose radioactivity allows the newly synthesized DNA to be visualized by autoradiography.

Next, each tube receives an excess of the four nonradioactive dNTP molecules and a small amount of one of the four ddNTPs. For example, the A reaction tube receives an excess of nonradioactive dTTP, dGTP, dCTP, and dATP mixed with a small amount of ddATP. DNA polymerase is then added to the reaction mixture. As the polymerase replicates the DNA, it occasionally incorporates a ddATP residue instead of a dATP residue, and synthesis of the growing DNA chain is terminated. Random incorporation of ddATP results in the production of newly synthesized DNA fragments of different lengths, each ending with A (i.e., ddA). The length of each fragment corresponds to the distance from the 5′-end of the primer to one of the adenine residues in the sequence.

Adding a different dideoxyribonucleotide to each reaction tube produces a different set of fragments: ddTTP produces fragments that terminate with T, ddGTP with G, and ddCTP with C. The newly synthesized chains from each sequencing reaction are separated from the template DNA.

Finally, the mixtures from each sequencing reaction are subjected to electrophoresis in adjacent lanes on a sequencing gel, where the fragments are resolved by size. The sequence of the DNA molecule can then be read from an autoradiograph of the gel.


This technique has also been modified to allow automation for high throughput applications like genomic sequencing. Instead of using radioactivity automated sequencing relies on fluorescently labeled dideoxynucleotides (four colors, one for each base) to detect the different chain lengths. In this system the gel is “read” by a fluorimeter and the data are stored in a computer file. Additionally, the sequencing machine can also provide a graphic chromatogram that shows the location and size of each fluorescent peak on the gel as they passed the detector.


The bottom figure is from Wikipedia. The other figures and the text are from Horton, H.R., Moran, L.A., Scrimgeour, K.G., Perry, M.D., and Rawn, J.D. (2006) Principles of Biochemistry 4th edition, Pearson Prentice Hall, Upper Saddle River, New Jersey, USA.
© Laurence A. Moran, Pearson Prentice Hall

Atheists Are Smarter than Agnostics

 
Science proves it.


Monday, December 15, 2008

Why Everyone Should Learn the Theory of Evolution

 
Why Everyone Should Learn the Theory of Evolution is the title of an editorial on the Scientific American website.

The editors begin by pointing out that Charles Darwin was a genius who deserves every bit as much recognition as Albert Einstein. I agree 100%. In my opinion Darwin is the greatest scientist who ever lived and it's about time we started to recognize his genius.

The rest of the editorial isn't as good. It's clear that the editors have a myopic view of evolution. They seem to think that the sort of evolution everyone should learn can be found in The Origin of Species.
But Darwin is so much more than just a quaint, Victorian historical figure whose bust in the pantheon deserves a place among those of other scientific greats. Theory needs to explain past, present and future—and Darwin’s does all three in a form that requires no simplifying translation. His theory is readily accessible to any literate person who allots a pleasurable interlude for On the Origin of Species, its prose sometimes bordering on the poetic: “... from so simple a beginning endless forms most beautiful and most wonderful have been, and are being, evolved.”
Now, you can learn a lot about evolution from reading Darwin's 1859 book. You can learn, for example, about natural selection and you can also learn about the inheritance of acquired characteristics.

You won't learn anything about genetics or biochemistry or developmental biology or bacteria or genomes or whether birds are related to dinosaurs.

The editors link to another article published in this month's Scientific American: The Evolution of Evolution. The article by Gary Stix attempts to explain Darwin's Living Legacy--Evolutionary Theory 150 Years Later. It doesn't do a very good job but at least it raises some interesting questions.
The concept of evolution as a form of branching descent from a common ancestor achieved a relatively rapid acceptance, but accommodation for natural selection came much more slowly, even within the scientific community. The hesitation was understandable. In his work, Darwin had not described a mechanism for inheritance, attributing it to minuscule, hypothetical “gemmules” that ejected from each tissue and traveled to the sex organs, where copies were made and passed to subsequent generations. It took until the decades of the 1930s and 1940s for natural selection to gain broad acceptance.

It was then that the modern synthesis emerged as an expansive framework that reconciled Darwin’s natural selection with the genetics pioneered by Gregor Mendel. In 1959, the centennial of the publication of Origin of Species, the place of natural selection seemed assured.

But in the ensuing years, the scope of evolutionary biology has had to broaden still further to consider such questions as whether the pace of evolution proceeds in fits and starts—a paroxysm of change followed by long periods of stasis. Do random mutations frequently get passed on or disappear without enhancing or diminishing fitness, a process called genetic drift? Is every biological trait an evolutionary adaptation, or are some characteristics just a random by-product of a physical characteristic that provides a survival advantage?

The field has also had to take another look at the notion that altruistic traits could be explained by natural selection taking place across whole groups. And as far as the origin of species, what role does genetic drift play? Moreover, does the fact that single-celled organisms often trade whole sets of genes with one another undermine the very concept of species, defined as the inability of groups of organisms to reproduce with one another? The continued intensity of these debates represents a measure of the vigor of evolutionary biology—as well as a testament to Darwin’s living legacy.
We know the answers to some of these questions. The modern version of evolution is the one that everyone should learn—not the 150-year-old version that Darwin wrote about.

If the editors of Scientific American don't understand the difference then our society is in a lot worse trouble than I imagined.



Monday's Molecule #101

 
This is the last Monday's Molecule for 2008. There will be a short Christmas break. Monday's Molecule will return on January 5th. As part of the Christmas celebrations, this week's molecule is a gift.

Your task is to identify this molecule and give it a biochemically accurate name (the IUPAC name would be perfect). The Nobel Laureate should be obvious once you identify the molecule.

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

There are four ineligible candidates for this week's reward: Ms. Sandwalk from Mississauga, Ontario, Canada, Alex Ling of the University of Toronto, Timothy Evans of the University of Pennsylvania, and John Bothwell of the Marine Biological Association of the UK in Plymouth, UK. John, Dale and Ms. Sandwalk have offered to donate the free lunch to a deserving undergraduate so the next two undergraduates to win and collect a free lunch can also invite a friend. Alex got the first one.

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 Laureate(s) 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.

UPDATE: The molecule is 2&prime,3′-dideoxycytidine 5′-monophosphate. This molecule differs from the normal cellular version of deoxycytidine because it is missing a second hydroxyl group at the 3′ position on the sugar. The triphosphate version of this molecule is a substrate for DNA polymerase and it will be incorporated into a growing DNA chain. However, once it is incorporated, the polymerization reaction stops because the 3′ hydroxyl group is essential for addition of the next nucleotide.

Dideoxynucleotides are used in the chain termination method of DNA sequencing developed by Frederick Sanger. Sanger received his second Nobel Prize in 1980 for developing this method, which remains the most popular method of DNA sequencing.

I was surprised that only a few people responded and even more surprised that some of the regulars didn't give a correct name for this molecule. There is no winner this week because I am being strict about nomenclature. If you didn't specify where the phosphate is attached (5′) or you used "cytosine" instead of "cytidine," then you don't get a free lunch! (Cytosine is the base, cytidine is the nucleoside.)


Conservatives Condone Torture, Liberals Don't

 
Let me make this perfectly clear—in my opinion, any society that condones and practices torture is a society in which the rights of all individuals are diminished. The rights of individuals and the goal of a just society are qualitative traits, not quantitative traits. If some people are deprived of those rights and if some people aren't part of the just society, then the "rights" don't exist and the society is not just. You can't have the right to fair treatment under the law in some situations but not in others. That's a mockery of justice.

Reuel Marc Gerecht is a former Central Intelligence Agency officer and a fellow at the Foundation for Defense of Democracies (FDD). The leadership of FDD consists of people like Newt Gingrich, Bill Kristol, Steve Forbes, and Joe Lieberman. They are "small-c" conservatives. Mostly Republicans, I think (including Lieberman, the Republican-in-all-but-name).

Last Saturday Gerecht wrote an opinion piece in The New York Times in defense of torture [Out of Sight].

He starts off by defending extraordinary rendition. This is the tactic of sending suspected criminals to other countries where they can be tortured and then returned to the USA. The idea is to be able to deny that the USA is in violation of its own Constitution and respect for human rights.
Mr. Obama will soon face the same awful choices that confronted George W. Bush and Bill Clinton, and he could well be forced to accept a central feature of their anti-terrorist methods: extraordinary rendition. If the choice is between non-deniable aggressive questioning conducted by Americans and deniable torturous interrogations by foreigners acting on behalf of the United States, it is almost certain that as president Mr. Obama will choose the latter.
Aside from the fact that torture is legally and ethically wrong, there's three other slight problems with this tactic. First, who are they trying to deceive? Is there anyone with an IQ over 50 that can be fooled by extraordinary rendition?1 Second, there's very little evidence that torture works. Third, many innocent people have been tortured.

Canada is particularly sensitive about rendition because of Maher Arar. Arar, a Canadian citizen, was arrested in 2002 at Kennedy Airport in New York and send to Syria where he was tortured and confined for 10 months. He was subsequently released and the Canadian government has established that he is innocent [Canadian cleared of terrorism after rendition, torture in Syria].

We don't know how many other innocent people have been tortured but chances are the numbers are substantial. The problem with rendition is that the individuals are deprived of their right to face their accusers and prove their innocence. No respectable society should condone such behavior.

Gerecht then raises the standard canard that seems to be the last refuge of those who would violate people's rights.
However, troubles in Pakistan may well reverse Mr. Obama’s luck. He has said he intends to be hawkish about fighting Al Qaeda and the Taliban in Central Asia. So, let us suppose that he increases the number of Special Forces raids into Pakistan, and those soldiers capture members of Al Qaeda and their computers, and learn that the group has advanced plans for striking American and European targets, but we don’t know specifically where or when.

What would Mr. Obama do? After all, if we’d gotten our hands on a senior member of Al Qaeda before 9/11, and knew that an attack likely to kill thousands of Americans was imminent, wouldn’t waterboarding, or taking advantage of the skills of our Jordanian friends, have been the sensible, moral thing to do with a holy warrior who didn’t fear death but might have feared pain?
No, Mr. Gerecht, torture is not a sensible, moral thing to do. It is stupid and immoral.

Stupid because the chances of finding out useful information under such circumstances are slim to zip. Stupid because under the Golden Rule we are putting the lives of all of our citizens at risk when they are captured by the bad guys. Stupid because it is contrary to the very thing that we are supposed to be fighting for. Stupid because the Americans who carry out rendition can be, and should be, put in jail. (I would even advocate that those who advocate breaking the law as almost as guilty.)

Immoral because .... never mind, he wouldn't know morality if it bit him on the posterior.

This issue is important in Canada for another reason. Our recently appointed Liberal leader, Michael Ignatieff, has a somewhat checkered history of modest support for torture. Recently his writings have been more clear about his opposition to torture while pointing out the moral dilemma [If torture works ...]. I'm going to quote extensively from his essay because this is a man who will be Prime Minister of Canada.
It is difficult to think about torture honestly. In a recent article on the interrogation techniques employed by the US, the writer Mark Bowden observed that few "moral imperatives make such sense on a large scale, but break down so dramatically in the particular." The moral imperative—do not torture, any time, anywhere, in any circumstances—is mandated by the UN convention against torture and other cruel, inhuman or degrading treatment or punishment. "No exceptional circumstances whatsoever, whether a state of war or a threat of war, internal political instability or any other public emergency," says the convention, can "be invoked as a justification of torture." That terrorists themselves torture does not change these imperatives. Our compliance does not depend on reciprocity.

.....

Elshtain justifies coercive interrogation using a complex moral calculus of "dirty hands": good consequences cannot justify bad acts, but bad acts are sometimes tragically necessary. The acts remain bad, and the person must accept the moral opprobrium and not seek to excuse the inexcusable with the justifications of necessity.

My own work on "lesser evils" brings me close to the Elshtain position. I agree with her that necessity may require the commission of bad acts, which necessity, nevertheless, cannot absolve of their morally problematic character—but I still have a problem. If one enumerates the forms of coercive interrogation that have been judged to be inhuman and degrading by the Israeli and the European courts—hooding, holding subjects in painful positions, exposing them to cold or heat or ear-splitting noise—these techniques also seem unacceptable, though at a lower threshold of awfulness, than torture. Like Elshtain, I am willing to get my hands dirty, but unlike her, I have practical difficulty enumerating a list of coercive techniques that I would be willing to have a democratic society inflict in my name. I accept, for example, that a slap is not the same thing as a beating, but I still don't want interrogators to slap detainees because I cannot see how to prevent the occasional slap deteriorating into a regular practice of beating. The issue is not, as Elshtain implies, that I care overmuch about my own moral purity but rather that I cannot see any clear way to manage coercive interrogation institutionally so that it does not degenerate into torture.

So I end up supporting an absolute and unconditional ban on both torture and those forms of coercive interrogation that involve stress and duress, and I believe that enforcement of such a ban should be up to the military justice system plus the federal courts. I also believe that the training of interrogators can be improved by executive order and that the training must rigorously exclude stress and duress methods.

Two significant problems remain. First of all, there is the problem of the exceptional case, one where lives can be saved by the application of physical methods that amount to torture. "Ticking bomb cases" cannot be wished away. They might arise especially where an American or European city faced the threat of WMD. An outright ban on torture and coercive interrogation leave a conscientious security officer with little choice but to disobey the ban. In this event, as the Israeli supreme court has said, even a conscientious agent acting in good faith to save lives should be charged with a criminal offence and be required to stand trial. At trial, a defence of necessity could be entered in mitigation of sentence, but not to absolve or acquit. This is the only solution I can see that remains consistent with an absolute ban on torture and coercive interrogation. Let us not pretend that the enforcement of this rule would be easy. Where the threat could be shown to be genuine, it seems evident that few legal systems would punish such a conscientious offender. So an outright ban on torture creates the problem of the conscientious offender. This is a small price to pay for a ban on torture.

Does an outright ban on torture and coercive interrogation meet the test of realism? Would an absolute ban on torture and coercive interrogation using stress and duress so diminish the effectiveness of our intelligence-gathering that it would diminish public safety? It is often said—and I argued so myself—that neither coercive interrogation nor torture is necessary, since entirely lawful interrogation can secure just as effective results. There must be some truth to this. Israeli interrogators have given interviews assuring the Israeli public that physical duress is unnecessary. But we are grasping at straws if we think this is the entire truth. As Posner and others have tartly pointed out, if torture and coercion are both as useless as critics pretend, why are they used so much? While some abuse and outright torture can be attributed to individual sadism, poor supervision and so on, it must be the case that other acts of torture occur because interrogators believe, in good faith, that torture is the only way to extract information in a timely fashion. It must also be the case that if experienced interrogators come to this conclusion, they do so on the basis of experience. The argument that torture and coercion do not work is contradicted by the dire frequency with which both practices occur. I submit that we would not be "waterboarding" Khalid Sheikh Mohammed—immersing him in water until he experiences the torment of nearly drowning—if our intelligence operatives did not believe it was necessary to crack open the al Qaeda network that he commanded. Indeed, Mark Bowden points to a Time report in March 2003 that Sheikh Mohammed had "given US interrogators the names and descriptions of about a dozen key al Qaeda operatives believed to be plotting terrorist attacks." We must at least entertain the possibility that the operatives working on Sheikh Mohammed in our name are engaging not in gratuitous sadism but in the genuine belief that this form of torture—and it does qualify as such—makes all the difference.

If they are right, then those who support an absolute ban on torture had better be honest enough to admit that moral prohibition comes at a price. It is possible, at least in theory, that subjecting interrogators to rules that outlaw torture and coercive interrogation, backed up by punishment if they go too far, will create an interrogation regime that allows some interrogation subjects to resist divulging information and prevents our intelligence services from timely access to information that may save lives.

If there is a significant cost to an outright ban on coercive interrogation and torture, what can possibly justify it? Many of the arguments that human rights activists make in justification amount to the claim that torture shames their moral identity as human beings and as citizens, and that they do not wish such acts to be committed in their names. Other citizens in a democracy may not value their own moral scruple over the collective interest in having accurate security information, even if collected by dubious means. It may be obvious to human rights activists how to adjudicate these claims, but it is not obvious to me. That is, I do not see any trumping argument on behalf of the rights and dignity of security detainees that makes their claims prevail over the security interests (and human right to life) of the majority. The best I can do is to relate the ban on torture to the political identity of the democracies we are trying to defend—by claiming that democracies limit the powers that governments can justly exercise over the human beings under their power, and that these limits include an absolute ban on subjecting individuals to forms of pain that strip them of their dignity, identity and even sanity.

We cannot torture, in other words, because of who we are. This is the best I can do, but those of us who believe this had better admit that many of our fellow citizens are bound to disagree. It is in the nature of democracy itself that fellow citizens will define their identity in ways that privilege security over liberty and thus reluctantly endorse torture in their name. If we are against torture, we are committed to arguing with our fellow citizens, not treating those who defend torture as moral monsters. Those of us who oppose torture should also be honest enough to admit that we may have to pay a price for our own convictions. Ex ante, of course, I cannot tell how high this price might be. Ex post—following another terrorist attack that might have been prevented through the exercise of coercive interrogation—the price of my scruple might simply seem too high. This is a risk I am prepared to take, but frankly, a majority of fellow citizens is unlikely to concur.
I'm more skeptical than Ignatieff about the efficacy of torture. Just because lots of people do it does not sound like a good argument for defending the usefulness of torture.

Nevertheless, when it comes to the bottom line, I'm with Michael Ignatieff, "We cannot torture ... because of who we are." If there's a price to be paid for doing the right thing then I'm prepared to pay it and suffer the consequences.


1. Apparently patriotic conservatives are easily fooled—that's why I set the cutoff IQ so high.

[Hat Tip: daimnation! via Canadian Cynic]

Sunday, December 14, 2008

Women of The View Discuss Evolution

 
PZ Myers posted this on Pharyngula but in case some of you haven't seen it there, I though I'd post it too.

I find it really shocking that people would talk like this on television knowing that they're being watched by millions of people. Surely they realize that what they're saying conflicts with the consensus among scientific experts? I can understand how they might justify their anti-science position in their own minds in the privacy of their church or home but in public?

They must have a very low opinion of scientists.



Scientific American: The Evolution of Evolution

 
The latest edition of Scientific American is all about "The Evolution of Evolution."

Here's how the editor-in-chief, John Rennie introduces the articles.
When Charles Darwin published "On the Origin of Species" in 1859, he touched off a Cambrian explosion in evolutionary thought. Naturalists had theorized about evolution for centuries before him, but their ideas were generally unfruitful, untestable or wrong. Darwin's breakthrough insight was not that a simple mechanism—natural selection—made evolution possible. Rather it was that in organisms whose environments changed nonrandomly and whose reproductive success in that environment depended on inherited traits, evolution became inevitable.

In the decades that followed, Darwin's ideas connected up with the nascent field of genetics and then, at an ever quickening pace, with molecular biology, ecology and embryology. The explanatory power his concepts proved irresistible. Today 200 years after his birth and 150 years after "Origin of Species," Darwin's legacy is a larger, richer, more diverse set of theories than he could have imagined.
You will enjoy reading the articles to see exactly what Scientific American means when they talk of a "richer, more diverse set of theories." Here's the list.

SciAm Perspectives: A Theory for Everyman
; by The Editors; 1 Page
Evolution should be taught as a practical tool for understanding drug resistance and the price of fish.
Darwin's Living Legacy; by Gary Stix; 6 Pages
A Victorian amateur undertook a lifetime pursuit of slow, meticulous observation and thought about the natural world, producing a theory 150 years ago that still drives the contemporary scientific agenda.
Testing Natural Selection; by H. Allen Orr; 8 Pages
Biologists working with the most sophisticated genetic tools are demonstrating that natural selection plays a greater role in the evolution of genes than even most evolutionists had thought.
From Atoms to Traits; by David M. Kingsley; 8 Pages
Charles Darwin saw that random variations in organisms provide fodder for evolution. Modern scientists are revealing how that diversity arises from changes to DNA and can add up to complex creatures or even cultures.
The Human Pedigree; by Kate Wong; 4 Pages
Some 180 years after unearthing the first human fossil, paleontologists have amassed a formidable record of our forebears.
This Old Body; by Neil H. Shubin; 4 Pages
Evolutionary hand-me-downs inherited from fish and tadpoles have left us with hernias, hiccups and other maladies.
What Will Become of Homo sapiens?; by Peter Ward; 6 Pages
Contrary to popular belief, humans continue to evolve. Our bodies and brains are not the same as our ancestors’ were—or as our descendants’ will be.
Four Fallacies of Pop Evolutionary Psychology; by David J. Buller; 8 Pages
Some evolutionary psychologists have made widely popularized claims about how the human mind evolved, but other scholars argue that the grand claims lack solid evidence.
Evolution in the Everyday World; by David P. Mindell; 8 Pages
Understanding of evolution is fostering powerful technologies for health care, law enforcement, ecology, and all manner of optimization and design problems.
The Science of Spore; by Ed Regis; 2 Pages
A computer game illustrates the difference between building your own simulated creature and real-life natural selection.
The Latest Face of Creationism; by Glenn Branch and Eugenie C. Scott; 8 Pages
Creationists who want religious ideas taught as scientific fact in public schools continue to adapt to courtroom defeats by hiding their true aims under ever changing guises.


Gene Genie #41

 
The 41th edition of Gene Genie has been posted at ScienceRoll [Gene Genie #41: Carnivalome].
Gene Genie is the blog carnival of clinical genetics and personalized medicine. I’ve received more than 25 submissions for this edition which is dedicated to the human genome and videos in clinical genetics.
The beautiful logo was created by Ricardo at My Biotech Life.

The purpose of this carnival is to highlight the genetics of one particular species, Homo sapiens.

Here are all the previous editions .....
  1. Scienceroll
  2. Sciencesque
  3. Genetics and Health
  4. Sandwalk
  5. Neurophilosophy
  6. Scienceroll
  7. Gene Sherpa
  8. Eye on DNA
  9. DNA Direct Talk
  10. Genomicron
  11. Med Journal Watch
  12. My Biotech Life
  13. The Genetic Genealogist
  14. MicrobiologyBytes
  15. Cancer Genetics
  16. Neurophilosophy
  17. The Gene Sherpa
  18. Eye on DNA
  19. Scienceroll
  20. Bitesize Bio
  21. BabyLab
  22. Sandwalk
  23. Scienceroll
  24. biomarker-driven mental health 2.0
  25. The Gene Sherpa
  26. Sciencebase
  27. DNA Direct Talk
  28. Greg Laden’s Blog
  29. My Biotech Life
  30. Gene Expression
  31. Adaptive Complexity
  32. Highlight Health
  33. Neurophilosophy
  34. ScienceRoll
  35. Microbiology Bytes
  36. Human Genetic Disordrs
  37. The Genetic Genealogist
  38. ScienceRoll
  39. Genetics & Health
  40. Human Genetics Disorders
  41. ScienceRoll


Saturday, December 13, 2008

Epigenetics at SEED

Epigenetics is one of the latest fads in biology. It arises out of evo-devo and its proponents tell us that epigenetics will transform the way we think about evolution. I've been trying to understand this phenomenon starting with some simple questions about what, exactly, is so new. I'd be happy if someone could just explain what they mean by "epigenetics" [Epigenetics in New Scientist, Epigenetics Revisited, Epigenetics, Epigenetics Again].

Eva Jablonka is a Professor at the Cohn Institute for the History and Philosophy of Science and Ideas at Tel-Aviv University (Israel). Jablonka was one of the 16 people who met in Alterberg, Austria last summer to discuss the faults in modern evolutionary biology. She writes an article entitled "Extending Darwinism" in the latest issue of SEED magazine.
I and several other biologists believe the MS [Modern Synthesis1] is in need of serious revision. Growing evidence indicated that there is more to heredity than DNA, that heritable non-DNA variations can take place during development, sometimes in response to an organism's environment. The notion of soft inheritance is returning to reputable scientific inquiry. Moreover, there seem to be cellular mechanisms activated during periods of extreme stress that trigger bursts of genetic and non-genetic heritable variations, inducing rapid evolutionary change. These realizations promise to profoundly alter our view of evolutionary dynamics.
Nothing new here, folks. It's just the same old gibberish that we've been hearing for the past several years.

If there is as much natural variation induced by environmental factors as lab studies suggest, then rapid evolutionary change could occur without any genetic change at all.

Eva Jablonka
But there is one thing that's worth noting. Eva Jablonka has done what few of her fellow epigeneticists have attempted. She defines what she means by epigenetics!
Epigenetics is a term that includes all the processes underlying developmental flexibility and stability, and epigenetic inheritance is part of this. Epigenetic inheritance is the transmission of developmental variations that have nothing to do with changes in the DNA base sequences. In its broad sense, it covers the transmission of any differences that do not depend on gene differences, so it encompasses the cultural inheritance of different religious beliefs in humans and song dialects in birds. It even includes the developmental legacies that a young mammal may receive from its mother through her placenta or milk—transmitted antibodies, for example, or chemical traces that tell the youngsters what the mother has been eating and, therefore, what they should eat.
Yes, but does it include the kitchen sink?

The good thing about incorporating these things into evolutionary theory is that it solves the problem of creationism. As long as creationism is passed on from parent to child then it becomes part of evolution. Isn't that cool?


1. Her version of the Modern Synthesis only includes natural selection.

A Holy Alliance?

 
Mario Beauregard is an Associate Researcher in the Departments of Radiology and Psychology at the University of Montreal in Montreal, Quebce, Canada. He is best known as the co-author of The Spiritual Brain with Denyse O'Leary.

Jeffrey M. Schwartz is a research psychiatrist at the School of Medicine at the University of California at Los Angeles (USA). He signed the Discovery Institute's "Scientific Dissent from Darwinism" statement.

Beauregard and Schwartz joined in a holy alliance to write a letter of protest to New Scientist concerning an article published a few months ago. The article was critical of people like Beauregard and Schwartz who mix religion and science.
Your writer's attempt to smear scientists who are looking for new directions, while perhaps entertaining, is a poor substitute for thoughtful coverage of a growing area.
Perhaps we should be looking to writers like Denyse O'Leary for thoughtful coverage?


The Problem with Microarrays

 
From The Endeavour by John D. Cook: Why microarray study conclusions are so often wrong and from Reproducible Results: Three reasons to distrust microarray results


[Hat Tip: A Blog Around the Clock]

Does Your Heart Bleed for Jodi?

 
Times are tough these days. People have lost their jobs and many are struggling to put food on the table and keep a roof over their heads. Christmas is not going to be a happy time in many households across North America.

The New York Times, bless its heart, is not unaware of what's going on. Lisa Foderaro has written an article that's sure to bring a tear to your eye as she documents the devastating effect of job loss on the life of a teenager [As the Rich Get Poorer, Teenagers Feel the Crunch ].
Jodi Hamilton began her senior year of high school in Woodcliff Lake, N.J., this fall on the usual prosperous footing. Her parents were providing a weekly allowance of $100 and paying for private Pilates classes, as well as a physics tutor who reported once a week to their 4,000-square-foot home.

But in October, Jodi’s mother lost her job managing a huge dental practice in the Bronx, then landed one closer to home that requires more hours for less money. Pilates was dropped, along with takeout sushi dinners, and Jodi’s allowance, which covers lunch during the week, slipped to $60. Instead of having a tutor, Jodi has become a tutor, earning $150 a week through that and baby-sitting.

“I just thought it would be responsible to get a job and have my own money so my parents didn’t have to pay for everything,” said Jodi, who is 17. “I always like to be saving up for something that I have my eye on — a ring, a necklace, a handbag.”
Later on in the article we hear about some other teenagers who have been forced to find a job.
Teenagers from working- and middle-class families are, of course, feeling similar — if not more acute — pressure. Sumit Pal, 17, a senior at Information Technology High School in Queens, said his parents cut his $5 weekly allowance two months ago after the deli where his father works started to lose business. Sumit was interviewed two weeks ago for a job at a company that sponsors rock bands.

“I don’t mind losing my allowance,” he said. “It goes toward other things, like groceries.”
How nice of Ms. Foderaro to mention that the lower classes are also, "of course," feeling the pinch.


[Hat Tip: Canadian Cynic pointed to this posting on The Vanity Press: Pitchforks and Torches Time]

Friday, December 12, 2008

What Is the Scientific Method?

 

There are lots of interesting things in this month's issue of SEED magazine. One of them is a survey of scientists in the USA, UK, France and Germany.

SEED magazine conducted a survey where it asked the following question of 1000 scientists in the USA, UK, France, and Germany: "Does the scientific method describe how you do science?" [SEED: State of Science].

81% said "yes."

I would answer "no" but my answer depends very much on what I think the question means. I think it's fair to use the common understanding of the "scientific method," the one that's taught in fifth grade.

Here's the simple version that's described on the Wikipedia site [Scientific Method].
  1. Use your experience: Consider the problem and try to make sense of it. Look for previous explanations. If this is a new problem to you, then move to step 2.
  2. Form a conjecture: When nothing else is yet known, try to state an explanation, to someone else, or to your notebook.
  3. Deduce a prediction from that explanation: If you assume 2 is true, what consequences follow?
  4. Test : Look for the opposite of each consequence in order to disprove 2. It is a logical error to seek 3 directly as proof of 2. This error is called affirming the consequent.
Is this what most people think about when they hear the term "scientific method"?

If you are a scientist, how would you have answered the SEED question and what definition of "scientific method" do you have in mind?


Religious Scientists

 
There are lots of interesting things in this month's issue of SEED magazine. One of them is a survey of scientists in the USA, UK, France and Germany.

SEED asked a total of 1000 scientists whether they were "atheist or agnostic," "practicing nonbelievers," "believers," or "spiritual" [SEED: State of Science].

Here's the result, in percent, for each of the four choices.

USA: atheist = 17%, nonbelievers = 6%, believers = 53%, spiritual = 24%
UK: atheist = 44%, nonbelievers = 10%, believers = 35%, spiritual = 11%
France: atheist = 50%, nonbelievers = 6%, believers = 39%, spiritual = 5%
Germany: atheist = 40%, nonbelievers = 24%, believers = 32%, spiritual = 4%

I find this surprising. The distribution isn't that much different from the general public in each of the countries. I was under the impression that scientists are considerably less religious than the society in which they live.

Perhaps this is because the SEED definition of scientist is more flexible than the one I would use. Here's the breakdown of their survey group.

Social Science: 24%
Medicine: 23%
Life Sciences: 15%
Engineering: 12%
Physical Sciences: 9%
Computer Science: 9%
Mathematics: 8%


Richard Cizik Resigns

 
Most of you have never heard of Richard Cizik. Let me explain why his resignation is important.

A few days ago I posted an opinion on framing and referred you to Matt Nisbet who claims that Richard Cizik is a good example of how to present science to the general public. Cizik is Vice President for governmental affairs of the National Association of Evangelicals (NAE). Nisbet thinks he is the top climate communicator [see Communicating the Truth about Climate Change].

I quoted from Nisbet's blog where he refers approvingly to a Cizik interview with Terry Gross.

Yesterday Christianity Today announced that Richard Cizik has been forced to resign his position in the National Association of Evangelicals [Richard Cizik Resigns from the National Association of Evangelicals]
Richard Cizik resigned Wednesday night as vice president for governmental affairs of the National Association of Evangelicals (NAE) during a week of growing uproar over his comments that he is shifting his views on same-sex unions.

"Although he has subsequently expressed regret, apologized, and affirmed our values, there is a loss of trust in his credibility as a spokesperson among leaders and constituencies," Leith Anderson, president of the NAE wrote to board members today. Cizik did not return calls for comment.

Last year, more than two dozen evangelical leaders sought to oust Cizik, who has been vice president for 28 years, because of his "relentless campaign" on global warming.

"For better or for worse, Rich became a great, polarizing figure," said Charles Colson of Prison Fellowship. "He was gradually, over a period of time, separating himself from the mainstream of evangelical belief and conviction. So I'm not surprised. I'm sorry for him, but I'm not disappointed for the evangelical movement."

Cizik spoke mostly on the environment in a December 2 interview with Terry Gross on National Public Radio's Fresh Air, but he made brief remarks about same-sex civil unions, gay marriage, and his early support of President-elect Barack Obama.

In a short portion of the program, Gross asked him, "A couple of years ago when you were on our show, I asked you if you were changing your mind on that. And two years ago, you said you were still opposed to gay marriage. But now as you identify more with younger voters, would you say you have changed on gay marriage?"

Cizik responded, "I'm shifting, I have to admit. In other words, I would willingly say that I believe in civil unions. I don't officially support redefining marriage from its traditional definition, I don't think."
I wonder if Matt still thinks that Richard Cizik is the best example of successful framing?


[Hat Tip: Friendly Atheist: Christian Leader Resigns Because of His Almost-Tolerant Views of Homosexuals]

Thursday, December 11, 2008

Noah's Ark

 
Yesterday I dropped a hint about a plastic model of Noah's Ark. I suggested it might make a good gift ... in case anyone was thinking about gifts.

Ms. Sandwalk was a bit insulted 'cause we already have a perfectly good ark that she made—complete with animals. Here's a photo of her work. I have to admit that it's a lot better than the plastic model.




Matt Nisbet Explains His Anti-Dawkins Spin

 
Here's Mat Nisbet explaining why Richard Dawkins is such an evil person. In the second part of this video he tries to explain why scientists don't like Matt Nisbet very much.

The most interesting question is near the end of the video when he states that no one would ever criticize the National Academies for misrepresenting science in order to make it seem compatible with religion. He knows that this is not true (e.g., An Example of Framing by Matt Nisbet). We have a word for people who delberately say things they know to be untrue ... it's called framing.





Belief in Astrology Falls to Second Last Place!

 
According to the latest Harris Poll only 31% of Americans believe in astrology and only 24% believe that they were once another person.

Other interesting facts are that a substantial majority of Americans believe in multiple supernatural beings (polytheism). Besides the regular God, they believe in angels and the devil.

 Believe InDon't
Believe In
Not Sure
     %    %    %
God   80   10   9
Miracles   75   14   12
Heaven   73   14   13
Jesus is God or the Son of God   71   17   12
Angels   71   17   12
The resurrection of Jesus Christ   70   18   13
Survival of the soul after death   68   15   17
Hell   62   24   13
The Virgin birth   61   24   15
The devil   59   27   14
Darwin’s theory of evolution   47   32   22
Ghosts   44   39   17
Creationism   40   31   29
UFOs   36   39   25
Witches   31   54   14
Astrology   31   51   18
Reincarnation–that you were once another person   24   53   23

In other news, 37% believe that the Old Testament is the word of God but only 14% believe The Torah is the word of God.

15% say they are not at all religious and 10% don't beleive in God.