Happy Birthday Universe!

 
Bishop James Ussher (1581 - 1656) was Archbishop of Armagh and Primate of All Ireland. He calculated that the universe was created on this day in 4004 BC, or more correctly the night before this day.

In addition to astute Biblical scholarship, the calculation required a knowledge of ancient history. Ussher's estimates of ancient dates were pretty good for his time.

We now know that his calculation was flawed because the Bible is completely wrong about creation but it is unfair to make fun of Ussher based on what we learned several centuries later.

Happy Birthday Universe.

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Nobel Laureate: Hermann Muller

 

The Nobel Prize in Physiology or Medicine 1946.

"for the discovery of the production of mutations by means of X-ray irradiation"

Hermann Joseph Muller (1890 - 1967) won the Noble Prize for showing that X-rays could induce mutations in Drosophila melanogaster. He was able to isolate and map specific mutations caused by X-rays showing that these were stable genetic changes.

For a brief description of the technique, see Hermann Muller Invented Balancer Chromosome.

The significance of Muller's work is described in the presentation speech on the Nobel rize website.

THEME:
Nobel Laureates

It was known, already at the turn of the century, that apparently sudden changes may appear spontaneously in the hereditary mass, which result in changes in the characteristics of the organism. We now know that these changes may be of different types, and among them occur also disturbances in individual genes. These are very rare, however. Even in such a convenient experimental object as the banana fly, introduced by Morgan, where the generations succeed each other rapidly, and thousands of flies can be examined, it is only seldom that mutations are observed. Muller grappled with the task of trying to change the frequency of mutations. He first created procedures, technically extremely elegant, by which the mutation frequency could be measured exactly. When this task - which took several years - had been completed, the effect of different agents on the frequency of mutations was investigated, and the discovery for which the Nobel Prize is now awarded was made, viz. that irradiation with X-rays evokes large numbers of mutations. Experiments could be arranged, for instance, so that nearly 100 per cent of the offspring of irradiated flies showed mutations. Thus a possibility had been created for the first time of influencing the hereditary mass itself artificially.

This discovery aroused a great sensation already when it was first published in 1927 and rapidly led to a great deal of work of different kinds and in the most varied directions. The mechanism of the effect of rays was studied by many research workers, with Muller at their head. Greatly simplified X-ray irradiation, as also ionizing irradiation, could be likened in general to a shower of infinitely small (even compared with the individual cell) but highly explosive grenades, which explode at different spots within the irradiated organism. The explosion itself (or the fragments it throws up) tears the structure of the cell to pieces or disturbs its arrangement. If such an explosion happens to take place in or close to a gene, its structure, and therewith also its effect on the organism, may be changed.

Muller's discovery of the induction of mutations by means of rays has been of tremendous importance for genetics and biology in general.

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The Christian Man's Evolution

 
A posting on the Scientific American website describes the view of Francisco J. Ayala, a man who was ordained as a Dominican priest who is also an excellent scientist [The Christian Man's Evolution: How Darwinism and Faith Can Coexist .

Here's an excerpt ...

Ayala graduated in physics at the University of Madrid, then worked in a geneticist’s lab while studying theology at the Pontifical Faculty of San Esteban in Salamanca, Spain. By his ordination in 1960 he had already decided to pursue science instead of a ministerial role. At the monastery Darwinism had never been perceived as an enemy of Christian faith. So a year later, when Ayala moved to New York City to pursue a doctorate in genetics, the prevailing U.S. view of a natural hostility between evolution and religion was a shock.

Ever since, Ayala has attempted to address religious skepticism about Darwin’s theory. At first, he recalls, his scientific colleagues were wary and took the position that researchers should not engage in religious discussions. By 1981, when the Arkansas legislature voted to give creationism equal time in schools, the mood began to change. The National Academy of Sciences prepared an amicus curiae brief for a Supreme Court case on the Louisiana “Creation Act” and asked Ayala to lead the effort. The booklet became the 1984 Science and Creationism: A View from the National Academy of Sciences.

For the second edition in 1999 Ayala presented the idea of incorporating the words of some theologians but recalls, “I was almost eaten alive.” In the third edition, published this year, one section features statements by four religious denominations and three scientists on the compatibility of evolution with religious beliefs.

I've already commented on the National Academys' sellout to political correctness and on the fact that Ayala was Chair of the committee [Richard Dawkins on the Michael Reiss Affair] [National Academies: Science, Evolution and Creationism]. The fallacy here is something called The Doctrine of Joint Belief.

That's not what I want to comment on today. I want to draw your attention to the use of "Darwinism" in the title of the article and to "Darwin's theory" in the body of the article. The author, Sally Lehrman¹, should know better. If she's going to write for Scientific American then she better learn that the correct terms are "evolution" and "evolutionary theory." The editors of Scientific America should know better, but then what can you expect from a magazine that has fallen so far from its heydays in the 60s and 70s?

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1. "Sally Lehrman teaches journalism in the public interest at Santa Clara University."

Hermann Muller Invented the Balancer Chromosome

Since writing about Balancer Chromosomes, I've gotten several email messages pointing out things I missed. Thanks to everyone who responded. It's what makes this blog worthwhile.

Quite a few readers pointed out that balancer chromosomes were invented a very long time ago by Hermann Muller. Muller won the Nobel Prize in 1946 for discovering mutagenesis by X-rays.

Dale Hoyt, a fly geneticist, sent me a description of Muller's experiment and he has given me permission to post it.

The first Nobel laureate who used balancers in his work was Hermann J. Muller. He used a strain of D. melanogaster that was heterozygous for an X-chromosome inversion. This suppresses crossing over between the normal X and the X carrying the inversion during meiosis. A single crossover within the inverted segment will generate a "bridge" at meiosis I, causing the non-crossover chromatid to preferentially segregate to the future ovum. In Muller's work the inverted X was marked with the dominant eye shape mutation, Bar, and carried a recessive lethal allele.¹ A female heterozygous for the marked inverted chromosome and a "wild type" chromosome will produce only 1/2 the normal number of male progeny and they will all be wild type. This is because 1/2 the males die because they receive the Bar chromosome and are hemizygous for the lethal. The inversion heterozygosity prevents recombination between the Bar locus and the lethal locus. Muller used this stock, called "ClB", to show that X-irradiation increased the frequency of mutation to lethal genes on the X-chromosome. Irradiated male flies were individually mated to the ClB females. Their Bar-eyed female offspring (heterozygous for the inversion and the irradiated X-chromosome) were mated to their brothers. If no males were produced from this cross then the irradiated male transmitted an X chromosome with a lethal mutation. It was easy to score the crosses—just look at the bottle and if there were no males then Muller knew that he had a radiation induced lethal.

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1. l(1)C, associated with the left breakpoint of the inversions. Presumably the break disrupts a gene required for viability. The gene must be known by now.

[Photo Credit: WIRED]

The Lactose Paradox

The lac operon in E. coli consists of three genes (lacZ, lacY and lacA) transcribed from a single promoter. The lacZ gene encodes the enzyme β-galactosidase, an enzyme that cleaves β-galactosides. Lactose is a typical β-galactoside and the enzyme cleaves the disaccharide converting it to separate molecules of glucose and galactose. These monosacharides can enter into the metabolic pool of the cell where they can serve as the sole source of carbon.

LacY encodes a famous transporter called lactose permease. It is responsible for importing βgalactosides. The lacA gene encodes a transacetylase that is responsible for detoxifying the cell when it takes up poisonous β-galactosides.

[from The Lac Operon]

Transcription of the lac operon begins when RNA polymerase binds to the P_lac promoter. The long polycistronic mRNA (wavy line) is translated to produce the three proteins.

In the absence of lactose, transcription of the lac operon is blocked by a repressor protein that binds to two sites (O₁ and O₂) preventing RNA polymerase from transcribing the operon [Repression of the lac Operon].

When the bacteria encounter lactose, transcription of the lac operon is induced but since the operon has a weak promoter not much protein will be produced as long as glucose is present. Glucose is always the preferred carbon source. In the absence of both glucose and lactose the operon is maximally induced by the activator CRP-cAMP.

Lactose induces transcription by causing a change in the structure of the repressor so that it no longer binds to DNA. When that happens, RNA polymerase can transcribe the operon.

Here's the paradox. Lactose can't enter the cell unless it's transported across the membrane by the permease and the permease can only be made if the lac operon is transcribed. Furthermore, lactose itself doesn't bind to the lac repressor causing it to detatch from its binding sites. Instead, the actual inducer is allolactose, a modified form of lactose that can only be synthesized inside the cell by the enzyme β-galactosidase. β-galactosidase can only be synthesized if the operon is transcribed.

This is known as the "lactose paradox." It seems you can't induce the operon unless there's allolactose present and the only way to get allolactose is to take up lactose via the permease and convert it to allolactose via β-galactosidase.

The "paradox" was explained many decades ago when it was discovered that the lac operon is transcribed at least once whenever the lac repressor dissociates from its binding sites. The lac repressor is a highly specific DNA binding protein that binds very tightly to O₁ and O₂. But no protein can bind forever. When it dissociates, an mRNA is made and some permease and some β-galactosidase is synthesized. The repressor quickly re-binds and transcription is blocked.

The effect of this "escape" synthesis is that there will always be a few molecules of permease and a few molecules of β-galactosidase inside the cell. When the cell encounters lactose in the medium enough can be taken up and converted to allolactose to induce the operon.

A paper published in this week's issue of Science looked at the number of permease molecules that had to be present in order to induce transcription of the lac operon and discovered that there had to be about 300 molecules present. Some bacterial cells had fewer molecules of permease, by chance, so the repressor remained bound to DNA. Other cells had more than 300 molecules of permease so transcription of the operon was induced and many more molecules of permease were synthesized (Choi et al. 2008).

This is an interesting result but it might not be worth blogging about except for one thing. Our friendly IDiot DaveScot decided to use this paper to prove that evolution is wrong!! You can read all about it on Panda's Thumb: Scientific Vacuity of ID: Lactose Digestion in E. coli.

There's one more wrinkle to this story. Lactose is probably not the main substrate for β-galactosidase and it's quite likely that a typical E. coli cell never sees lactose. When they're not inside a human gut, E. coli cells won't ever encounter lactose. Even when they're living inside a friendly human, it will most often be an adult and throughout most of evolutionary history human adults did not consume milk. E. coli usually does not make up a significant proportion of the bacteria in nursing infants.

So, what is the real product of β-galactosidase and the real inducer of the lac operon? It's likely to be various other β-galactosides such as β-galactosyl glycerol. These are common breakdown products of plant membranes. They are transported efficiently by the permease but they can also be transported by a galactose permease that is always present in the bacteria membrane. Furthermore, β-galactosyl glycerol is a direct inducer of the lac operon. It binds directly to lac repressor so there's no need to convert it to something else (Egel, 1988).

While there may be a "lactose paradox" there is no "β-galactosyl glycerol paradox."

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Choi, P.J., Cai, L., Frieda, K., and Xie, X.S. (2008) A stochastic single-molecule event triggers phenotype switching of a bacterial cell. Science 322:442-6. [DOI: 10.1126/science.1161427]

Egel, R. (1988) The "lac" operon: an irrelevant paradox? Trends in Genetics 4:31.

Adoptees use DNA to find surname

 
This is an example of a real ethical problem. You might be surprised to learn that there aren't all that many "real" ethical problems. Most of the ones that are proposed are pseudo-ethical problems.

In this case, an article from BBC News describe how Adoptees use DNA to find surname.

Male adoptees are using consumer DNA tests to predict the surnames carried by their biological fathers, the BBC has learned.

They are using the fact that men who share a surname sometimes have genetic likenesses too.

By searching DNA databases for other males with genetic markers matching their own, adoptees can check if these men also share a last name.

This can provide the likely surname of an adoptee's biological father.

Why is this an ethical problem? Because it (potentially) involves a conflict between the wishes of two individuals. The adoptee wants to know who his biological parents are and the biological parents may wish to remain unknown.

As far as I'm concerned, the wishes of the biological parents have to be respected but with the widespread use of commercial DNA testing services, this wish can be circumvented by a determined adoptee.

Incidentally, these tests are also going to reveal who isn't your father, and that's also a problem.

There are many blogs acting as cheerleaders for the new commercial DNA testing services. One of them, The Genetic Genealogist seems to think that finding out who your father is, or isn't, is a good thing. That blog even points to a commercial company runnnig a program for adoptees with a success rate of more than 30% [More On Revealing Surnames Using Genetic Genealogy].

I think it's about time we started to think about the consequences.

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Gairdner Awards 2008

 
This is the week of the Gairdner awards. It's an excellent opportunity for undergraduates to see and hear some outstanding scientists. This week's lineup includes the 2008 winners and returning winners from past years.

Samuel Weiss: Adult neural stem cells
Victor Ambros: MicroRNA pathways in animal development
Gary Ruvkun: The tiny RNA pathways of C. elegans
Nahum Sonenberg: Translational control in biology and medicine
Harald zur Hausen: Infections as cancer risk factors
Ralph M. Steinman: Dendritic cells: A vehicle for vaccine development
Alan Bernstein: Progress towards an HIV vaccine
Sydney Brenner: An introduction
Craig Mello: RNAi from mechanism to medicine
Eric Olson: MicroRNa control of heart development and disease
George Church: Reading and writing genomes
Douglas Hanahan:Micro-RNA signatures in tumorigenesis
James S. Thomson: Exiting the pluripotent state, and back again
Gordon Keller: Directed differentiation of embryonic stem cells
Cynthia Kenyon: Genes and cells that regulate the lifespan of C. elegans
Leonard Guarente: Sirtuins, aging and diseases

The Gairdner Foundation presents a two-day symposium entitled "Minds That Matter" at the University of Toronto featuring academic lectures by Gairdner winners past and present, and other leading medical scientists. Attendance is open to anyone and is free of charge. All lectures are given at the Medical Sciences Auditorium on the University of Toronto campus in downtown Toronto.

TORONTO - UNIVERSITY OF TORONTO CAMPUS - MACLEOD AUDITORIUM
Date: Thursday, October 23, 2008

9:00 a.m.
Welcome: Dr. John Dirks, President, The Gairdner Foundation

Chair: Catharine Whiteside, Dean, Faculty of Medicine, Vice Provost Relations with Healthcare Institutions, University of Toronto

9:10 a.m.
Introduction: Dr. Freda Miller, Senior Scientist, Developmental & Stem Cell Biology, The Hospital for Sick Children, Professor, Department of Molecular Genetics, University of Toronto

Speaker: Dr. Samuel Weiss, Gairdner Laureate 2008, Professor of Cell Biology & Anatomy & Pharmacology & Therapeutics, Director Hotchkiss Brain Institute, University of Calgary, Calgary, AB, CA

Lecture: Adult neural stem cells: From basic science to therapeutic applications

9:50 a.m.
Introduction: Dr. Howard Lipshitz, Professor & Chair, Department of Molecular Genetics, Canada Research Chair (Tier 1) in Developmental Biology, University of Toronto, ON, CA

Speaker: Dr. Victor Ambros, Gairdner Laureate 2008, Professor of Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA

Lecture: MicroRNA pathways in animal development

10:30 a.m.Break

10:45 a.m.
Introduction: Dr. Craig Smibert, Department of Biochemistry, University of Toronto

Speaker : Dr. Gary Ruvkun, Gairdner Laureate 2008, Department of Genetics, Harvard Medical School, Boston, MA, USA

Lecture: The tiny RNA pathways of C. elegans

11:25 a.m.
Introduction: Dr. Tony Pawson, University Professor, University of Toronto, Programme in Molecular Biology & Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital

Speaker: Dr. Nahum Sonenberg, Gairdner Laureate 2008, Professor, Department of Biochemistry and McGill Cancer Centre, McGill University, Montreal, Quebec, CA

Lecture: Translational control in biology and medicine

12:05 p.m. LUNCH

1:00 p.m.
Chair: Dr. Jack Gauldie, University Professor, Department of Pathology & Molecular Medicine, McMaster University, Director, Centre for Gene Therapeautics, Hamilton

1:05 p.m.
Introduction: Dr. Joan Murphy, Head of the Division of Gynecologic Oncology, UHN, Associate Professor, Department of Obstetrics & Gynecology, University of Toronto

1:10 p.m.
Speaker: Prof. Harald zur Hausen, Gairdner Laureate 2008, Deutsches Krebsforschungszentrum, Heidelberg, Germany

Lecture: Infections as cancer risk factors

1:40 p.m.
Introduction: Dr. Michael Julius, Vice President Research, Sunnybrook Health Sciences Centre, Toronto, CA

Speaker: Dr. Ralph M. Steinman, GairdnerLaureate 2003, Henry G. Kunkel Professor & Sr. Physician,The Rockefeller University, New York, NY, USA

Lecture: Dendritic cells: A vehicle for vaccine development

2:20 p.m.
Introduction: Dr. Janet Rossant, Chief of Research & Senior Scientist, Research Institute, The Hospital for Sick Children, Toronto, ON, CA

Speaker: Dr. Alan Bernstein, Gairdner Wightman Laureate 2008, Executive Director, Global HIV Vaccine Enterprise, New York, NY, USA

Lecture: Global solutions for global challenges: Progress towards an HIV vaccine

3:00 p.m. Dr. John Dirks
Conclusion

ADVANCES IN MOLECULAR BIOLOGY: MICRO RNA'S, STEM CELLS AND AGING

TORONTO - UNIVERSITY OF TORONTO CAMPUS - MACLEOD AUDITORIUM
Friday, October 24, 2008

9:00 a.m.
Welcome: Dr. John Dirks, President & Scientific Director, The Gairdner Foundation
Professor Paul Young, Vice President Research, University of Toronto, CA

Chair: Dr. Michael Hayden, Canada Research Chair in Human Genetics & Molecular Medicine, University of British Columbia, Vancouver, B. C.

Speaker: Dr. Sydney Brenner, Gairdner Laureate 1978 & 1991, Nobel Laureate 2002, Distinguished Professor, The Salk Institute, San Diego, CA, USA

Lecture: An introduction

9:30 a.m.
Introduction: Dr. Martin Simard, Laval University Cancer Research Centre, Quebec City, Montreal, CA

Speaker: Dr. Craig Mello, Nobel Laureate 2006, Gairdner Laureate 2005, Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, MA, USA

Lecture: RNAi from mechanism to medicine

10:10 a.m. Break

10:30 a.m.
Introduction: Dr. David MacLennan, Gairdner Laureate 1991, Banting Best Department of Medical Research, University of Toronto, Charles H. Best Institute, Toronto, CA

Speaker: Dr. Eric Olson, Professor, Molecular Biology, Southwestern Medical School, Dallas, Texas

Lecture: MicroRNa control of heart development and disease

11:10 a.m.
Introduction: Dr. Steve Scherer, The Center for Applied Genomics, The Hospital for Sick Children, Toronto, CA

Speaker: Dr. George Church, Professor of Genetics, Harvard Medical School, Director of the Center for Computational Genetics, Boston, MA, USA

Lecture: Reading and writing genomes

11:50a.m. LUNCH

12:45 p.m.
Chair: Dr. Michael Tyers, CH Waddington Professor of Systems Biology, The University of Edinburgh, Edinburgh, ScotlandIntroduction: Dr. Samuel Aparicio, Professor of Breast Cancer Research, UBC/BCCA, BC Cancer Agency, Vancouver, BC

Speaker: Dr. Douglas Hanahan, Diabetes, and Comprehensive Cancer Centres, UCSF, San Francisco

Lecture: Micro-RNA signatures of the stages in multi-step tumorigenesis

1:25 p.m.
Introduction: Dr. Brenda Andrews, Terrence Donnelly Centre for Cellular & Biomolecular Research, University of Toronto, Toronto, CA

Speaker: Dr. James S. Thomson, Professor of Anatomy, University of Wisconsin Stem Cell & Regenerative Medicine Center, Wisconsin, USA

Lecture: Exiting the pluripotent state, and back again

2:05 p.m.
Introduction: Dr. Andras Nagy, Senior Investigator, Developmental Molecular Geneticist, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, CA

Speaker: Dr. Gordon Keller, Senior Scientist, Division of Stem Cell & Developmental Biology, Ontario Cancer Institute, Toronto, CA

Lecture: Directed differentiation of embryonic stem cells to functional tissues

2:45 p.m.
Introduction: Dr. Peter Lewis, Vice Dean, Research & International Relations, Faculty of Medicine, Professor of Biochemistry, University of Toronto, Toronto, CA

Speaker: Dr. Cynthia Kenyon, Director, Hillblom Center for Biology of Aging, UCSF, San Francisco, CA

Lecture: Genes and cells that regulate the lifespan of C. elegans

3:25 p.m.
Introduction: Dr. Jacques Drouin, Chair in Molecular Genetics, Intitut De Recherches Cliniques De Montreal, Montreal, Quebec

Speaker: Dr. Leonard Guarente, Harvard Medical School, Boston, MA, USA

Lecture : Sirtuins, aging and diseases

4:10 p.m.
Conclusion: Dr. John H. Dirks

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Monday's Molecule #93

 
What's going on here? Your task is to identify the experiment that led to this result. It's a short step from there to this week's Nobel Laureate(s). You just need to switch species.

Here's a hint: This week's Nobel Laureate(s) and last week's Nobel Laureates have something in common.

You need to describe what you see in the figure as accurately as possible. Then identify the Nobel Laureate(s).

The first one to correctly identify the figure and name the Nobel Laureate(s), 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: Brad Hersh of Clemsen University, Alex Ling of the University of Toronto, Haruhiko Ishii, and Bill Chaney of the University of Nebraska.

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 figure shows the result of an experiment where human cells in culture were irradiated with X-rays (Scherthan et al. 2008). There are two obvious chromosomal rearrangements. Breaks and deletions are common in X-ray treated cells. The Nobel Laureate is Hermann Muller who won the prize for creating mutants using X-rays. He worked with Drosophila melanogaster. Only one person got this one right and that person is ineligible.

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[Figure Credit: The figure is from Scherthan et al. (2008)]

Scherthana, H., Hieberb, L., Braselmannb, H., Meinekea, V., and Zitzelsberger, H. (2008) Accumulation of DSBs in γ-H2AX domains fuel chromosomal aberrations. Biochemical and Biophysical Research Communications 371:694-697. [doi:10.1016/j.bbrc.2008.04.127]

Periannan Senapathy Publishes in PLoS ONE

 
I first encountered Periannan Senapathy on the sci.bio.evolution newsgroup. He was promoting the idea that the various animal phyla arose independantly rather than from descent from a common ancestor.

Here's one of his early postings on sci.bio.evolution from Feb. 13, 1995"

As a molecular biologist and genome researcher, I have enjoyed following the many ongoing debates in this and other forums over evolution theory -- both as a whole, and various aspects thereof. My own work in genome mechanics and genetic molecular structures has yielded much evidence pertaining to these debates, and over the years I have published several of my findings in PNAS, J Molec Biol, J Biol Chem, Nucleic Acids Research, Science and other journals.

Until recently I have published these findings separately, although clearly they are all related. Now, however, I am publishing a single unified theory that incorporates all of these pieces -- and an enormous body of other evidence as well. This new unified theory proposes a radically alternative explanation for the origin and diversity of life on Earth, asserting that most of Earth's organisms must have originated independently in one primordial pond, and that the natural-selection mechanism described by evolution theories could have produced only minor variations among essentially similar species. These conclusions surely will provoke a lively debate in the scientific community, but a fair reading of the theory will show that it easily explains all of the available evidence -- molecular, biochemical, organismal and fossil -- and notably accommodates all of the contra-evolution evidence that has dogged evolutionists since Darwin.

His ideas were eventually published in 1994 in a book with the following provocative title: "Independent Birth of Organisms. A New Theory that Distinct Organisms Arose Independently from the Primordial Pond, Showing that Evolutionary Theories are Fundamentally Incorrect." The book was published by "Genome Publications."

Periannan Senapathy owns a company called "Genome International Corporation" which funds his work. The PLoS paper, for example, is funded by "Genome International Corporation" and the disclaimer reads, in part, "This project is purely an academic project, fulfilling the academic interest of the corresponding author, who owns the company." I don't know if the book is self-published.

The research article in PLoS ONE is ..

Regulapati, R., Bhasi, A., Singh. C.K., and Senapathy, P. (2008) Origination of the Split Structure of Spliceosomal Genes from Random Genetic Sequences. PLoS ONE 3(10): e3456 [doi:10.1371/journal.pone.0003456]

It address an old problem about the origin of introns. The consensus among scientists these days is that introns arose late and they are derived from insertions of self-splicing RNA's into coding regions. These were subsequently copied into DNA and integrated into the genome. The similarity between Group II introns and spliceosomal introns lends strong support to this model.

The fact that bacteria have very few introns is consistent with the idea that introns arose late in evolution. As is the fact that introns positions are not highly conserved, as one might expect if they arose early.

The Senapathy paper tries to make the case that introns are primitive and the human genome, with lots of introns, is more primitive than bacterial genomes, which have lost their introns.

Speaking of losing, this issue was resolved over ten years ago when the last holdouts for "introns early" conceded defeat. Senapathy has not come up with anything that even remotely rejuvenates that losing position.

On a more troubling note, it's beginning to look as if PLoS ONE is attracting the kooks who find it easy to get their work published in that forum. It won't be long before I stop reading papers, and abstracts, from PLoS ONE.

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It's the Sequence, Stupid!

The latest issue of Science has an article summarizing the research done by Wilson et al. (2008). The "perspectives" article, by Hilary A. Coller and Leonid Kruglyak has a provocative title It's the Sequence, Stupid!. The Wilson et al. paper casts doubt on one of the current fads in molecular biology, namely the claim that there's something called "epigenetics" that trumps DNA sequence when it comes to determining gene expression.

Here's the abstract from the Wilson et al. (2008) paper. You be the judge.

Homologous sets of transcription factors direct conserved tissue-specific gene expression, yet transcription factor–binding events diverge rapidly between closely related species. We used hepatocytes from an aneuploid mouse strain carrying human chromosome 21 to determine, on a chromosomal scale, whether interspecies differences in transcriptional regulation are primarily directed by human genetic sequence or mouse nuclear environment. Virtually all transcription factor–binding locations, landmarks of transcription initiation, and the resulting gene expression observed in human hepatocytes were recapitulated across the entire human chromosome 21 in the mouse hepatocyte nucleus. Thus, in homologous tissues, genetic sequence is largely responsible for directing transcriptional programs; interspecies differences in epigenetic machinery, cellular environment, and transcription factors themselves play secondary roles.

Grab some popcorn and a beer and sit back in your easy chair to watch how the evo-devo people talk themselves out of this one.

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Wilson, M.D., Barbosa-Morais, N.L., Schmidt, D., Conboy, C.M., Vanes, L., Tybulewicz, V.L.J. Fisher, E.M.C., Tavaré, S., and Odom. D.T. (2008) Species-Specific Transcription in Mice Carrying Human Chromosome 21. Science 322: 434-438. [DOI: 10.1126/science.1160930]

The Powerful 7%

 
Here's the result from a US Gallup Poll taken in May, 2007 [Religion].



Only 7% are potential atheists. How powerful are those people? PZ Myers has the answer from an article by Melanie Phillips on the financial crisis in America [Pharyngula: You mean it's all my fault?].

I see this financial breakdown, moreover, as being not merely a moral crisis but the monetary expression of the broader degradation of our values - the erosion of duty and responsibility to others in favour of instant gratification, unlimited demands repackaged as 'rights' and the loss of self-discipline. And the root cause of that erosion is 'militant atheism' which, in junking religion, has destroyed our sense of anything beyond our material selves and the here and now and, through such hyper-individualism, paved the way for the onslaught on bedrock moral values expressed through such things as family breakdown and mass fatherlessness, educational collapse, widespread incivility, unprecedented levels of near psychopathic violent crime, epidemic drunkenness and drug abuse, the repudiation of all authority, the moral inversion of victim culture, the destruction of truth and objectivity and a corresponding rise in credulousness in the face of lies and propaganda -- and intimidation and bullying to drive this agenda into public policy.

Makes you feel very sorry for the 93% who are being manipulated, doesn't it?

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Death to Apostates?

 
There was a conference in the UK where a number of former adherents of Islam talked about the fact that rejecting Islam is a very serious offense. Apostates can be killed.

A.C. Graying wrote an article about the conference. It was published in The Guardian and you can read it on RichardDawkins.net.

Now Nesrine Malik has responded in Friday's issue of The Guardian [Death for apostasy?].

Here's part of what she says ...

As a Muslim who has lived most of my life in Muslim countries, this picture is hard to recognise. I have several friends and family members who are non-believers and apart from some efforts to return them to the straight and narrow or at least go through the motions of religious observance, they have not come into any physical danger. A close friend – hitherto religious – only recently sent me a long, tortured email detailing his journey away from Islam and from all religion; he expressed no fears for his life or safety, merely trepidation at the prospect of acclimatising to this new God-free world view.

Although the Council of Ex-Muslims and AC Grayling depict the threat to life and limb as an indisputable fact, in reality there are differences of opinion among Muslim scholars (ostensibly the hard core of the religion) regarding the death penalty for apostates.

This is not to say that Muslim governments – and Arab ones in particular – have a tolerant view of apostasy but the death threat is invoked only rarely and more for political reasons rather than religion ones: to set an example or to save face as a proxy punishment for challenging the social or political status quo. While this is in no way acceptable, it is an extension of the general lack of enshrined civic human rights and evolved political institutions and processes – a historical, social and geo-political reality in many Muslim countries that makes a mockery of any comparison to the experience of those renouncing Christianity or Judaism.

It's of little comfort to an ex-Muslim to learn that there is disagreement within the Muslim community about whether they should be put to death or not. They take only a little more comfort from the fact that the death penalty is only used "rarely."

I admire Nesrine Malik for stating that killing apostates is "in no way acceptable" but she weakens her case a great deal by making excuses. Just because killing apostates is part of a larger intolerant viewpoint is an explanation, but not an excuse. Personally, I don't much care how the members of a cultural group run their lives but I draw the line when they interfere with others. People who leave the group are making a choice and they should be left alone.

Malik claims that many ex-Muslims try to make themselves into martyrs by claiming they have been threatened with death. They are just using "the emotive power of 'death for apostasy' to serve their own ends, be they personal or political." That may or may not be true—it probably is—but that's not the point.

The point is that outspoken Muslims like Nesrine Malik should make their opposition to 'death for apostasy' much clearer than just throwing away a phrase like "no way acceptable" to be immediately followed with a reason why it's understandable.

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The Toronto Star Editorial Cartoon

 
Today's editorial cartoon in The Toronto Star is worth sharing. If Canadians were allowed to vote in the US Presidential elections, the McCain people would have waved the white flag months ago.

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The Toronto Star Opposes PR, Again

 
I don't get it. Why are the editors of The Toronto Star against proportional representation? Their reasoning doesn't make sense.

Last year the editorial board opposed the Ontario referendum on electoral reform. Their arguments were so stupid and factually incorrect that "Public Editor" Kathy English was obliged to defend the newspaper's editorial opinions [The Toronto Star Defends Its Editorial Policy on MMP].

She didn't do a very good job.

Today The Star has an editorial opposing any proportional electoral system. The paper notes that a nationwide proportional system of voting would have given a different distribution of seats than the result of last Tuesday's election. They note that the Green party would have probably gotten a number of seats.

The editorial states, correctly, that we can't just recalculate the results based on Tuesday's voting because if we had voted under a proportional system people wold have voted differently. They say ...

Furthermore, the analysis is backward looking – transposing last week's results onto a new system. In all likelihood, if Canada had a system of proportional representation, the outcome would be very different, given the demographical and geographical diversity of the country. The pro-life Christian Heritage Party, for example, might win enough votes to get seats. And new parties might emerge to win seats – say, an Alberta First party or even ethnic parties.

So Harper might be kept in power by entering a coalition with pro-life and Alberta First parties. Now that, indeed, is a scary prospect.

This is scary. It looks like the editors of The Star are afraid of proportional voting because (horrors!) some people might elect MP's who truly represent their points of view.

Now we certainly can't have that in a democracy, can we?

The scare tactics are not based on rational analysis of what happens in other countries. Most Western democracies have moved into the 21st century and they find it beneficial to let the people have their say. Sticking with an unfair first-past-the -post system only breeds disillusionment and bitterness with a system that disenfranchises a majority of voters. (Voter turnout on Tuesday dropped below 60%.)

It's time for The Toronto Star to find new editors—ones who are as progressive as the newspaper they work for. The current editors are clearly not up to the job.

But maybe we shouldn't expect too much from editors who put Madonna on the front page under a banner about a rape probe.

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Barack Obama Is my Cousin!

 
George Bush and I share a common ancestor. This isn't as surprising as it might seem. Just about anyone in North America who has relatives from the British Isles will be able to trace some of their ancestors back five or six hundred years if they dig hard enough.

There's an excellent chance that you can connect at some point to several well-known lineages, usually those involving kings and queens. In my case I eventually hook up with Mary Stewart (1380 - 1458) who is the daughter of Robert III, King of Scotland. She married George Douglas (1376 - 1402).

George Bush descends from Mary's sister Elizabeth Stewart who married James Douglas, brother of George Douglas [The Ancestry of George Bush].¹

Now, most of you might not be too excited about being related to George Bush but here's the good news ... I'm also related to Barack Obama according to Obama and Bush related.

That's pretty cool. It explains a lot.

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1. It's possible that Bush descends from Beatrice Sinclair and not Elizabeth Stewart—the website is confusing. Even if this is an error there are several other connections.

If you build it, will they follow?

I'm going to subject you to one of my pet peeves.

The University of Toronto is in the process of replacing all its pathways. I really like the new style of path even though it's probably very expensive. It will improve the look of the university.

That's not the peeve. Look at the photograph below. It shows the newly completed paths leading up from the subway stop on the corner of University and College (behind me). The ramp is the easiest access to my building. Several hundred people a day walk up the path from the subway stop and up the ramp into the building.

When the stone masons were building the path I mentioned that the old pathway didn't align with the much newer ramp and, consequently, people were cutting across the grass in order to save time. That's why the grass is worn away at the base of the ramp. The guys who were laying the stones agreed that the fancy new path should at least clip off the corner by the lamp post to encourage people to follow it.

They were overruled by their supervisor who claims he doesn't have the authority to move or change the paths. So they simply replaced the old paved pathway with the nice new stone blocks and moved on.

How ridiculous. My pet peeve is this. You should build pathways where people actually walk and not where you want them to walk.

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What Questions about Evolution Can Students Safely Ask?

 
Denyse O'Leary is upset about the fact that students who challenge evolution may be perceived as being unworthy [Intelligent design and popular culture: What questions about evolution can students safely ask?].

She was impressed with the suggestions made by some photographer so she reproduced them on her blog. Here's what Densye O'Leary thinks will stump the average Professor. This is just for amusement on a Friday afternoon.

Don't argue against him. Agree with him. Then ask a question like one of those below:

1. I’d like to shut up those stupid IDers once and for all. Please tell me where I can find a book that shows clearly all the transitional fossil forms between fish and amphibians or reptiles and birds or some such major transition. I’d like to see it spelled out in detail with pictures and measurements and explanations of each fossil so I can crush those idiots.

2. I know that evolution is the most solidly proven theory in all of science, so please show me the mathematical proof of how random changes create information. I’m sure there must be one because this is a fundamental truth of evolution.

3. I know that in any system like life on earth that is open and receives outside energy the system will steadily grow more and more complex but I don’t really understand the physics of this. Could you explain it to me?

Just in case you've forgotten, this is what passes as the best evidence for Intelligent Design Creationism. We should think up a name to describe these people.

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Jonathan Wells reviews the Christiane Nüsslein-Volhard and Wieschaus Experiment

In his book, Icons of evolution, Jonathan Wells has ten chapters devoted to refuting evolution. This is typical behavior for an Intelligent Design Creationist. There's no mention anywhere in the book of positive evidence for intelligent design.

One of the chapters is "Four-Winged Fruit Flies." The main point of the chapter is that most of the Drosophila developmental mutations are lethal or extremely deleterious so they can't be transitional states in evolution. Yet, according to Wells, the textbooks are full of misleading statements claiming that morphological mutations supply the raw material for evolution. Wells says that there's no evidence for any beneficial mutations in spite of the fact that they have been looked for.

Yet the evidence cited in these textbooks falls far short of supporting those sweeping claims. To be sure, biochemical mutations lead to antibiotic and insecticide resistance, and human beings carrying the sickle-cell trait are more likely to survive malaria as infants. But only beneficial morphological mutations can provide the raw materials for morphological evolution, and evidence for such mutations is surprisingly thin. As we have seen, four-winged fruit flies do not provide the missing evidence, despite their current popularity.

If textbook-writers have no good examples of beneficial morphological mutations, it's not because biologists haven't been looking for them About the time that Lewis was studying Ultrabithorax, German geneticists Christiane Nüsslein-Volhard and Eric Wieschaus were using a technique called "saturation mutagenesis" to search for every possible mutation involved in fruit fly development. They discovered dozens of mutations that affect development at various stages and produce a variety of malformations. Their Herculean efforts earned them a Nobel prize (which they shared with Lewis), but they did not turn up a single morphological mutations that would benefit a fly in the wild. [my emphasis]

The experiment that was performed by Christiane Nüsslein-Volhard and Eric Wieschaus was designed to detect recessive lethal mutations that affected development. These kind of mutations are likely to identify genes that are essential for development. I described the experiment in a separate posting [Balancer Chromosomes].

Note that the experiment was specifically designed to detect deleterious mutations—lethal being about as deleterious as you can get. It could not possibly have detected beneficial mutations, as Wells claims, since these would have been discarded early on when the mutant lines were established.

Was the true purpose of the experiment a well-kept secret known only to insiders? Hardly. Everyone who read the papers knew that the screen was for recessive lethals. In her Nobel lecture Christiane Nüsslein-Volhard says,

In 1979, Eric Wieschaus and I, at that time in the EMBL, Heidelberg, had developed the methods for the large scale screening for embryonic lethal mutations in Drosophila. The screening procedure focused on the segmented pattern of the larval epidermis (8). In this and subsequent screens, a number of new genes acting in the embryo and required for the formation of a morphologically normal larva were discovered (9-11).

Should Wells have known this? You be the judge.

Wells has a Ph.D. in biology, molecular and cell biology, from the University of California, Berkeley (USA). He worked on embryology and evolution as a graduate student and subsequently as a post-doctoral fellow in the laboratory of Carolyn Larabell at Berkeley. He published two papers on development in 1996 and 1997.

It's safe to assume that Wells understands the basic principles of genetics and developmental biology.

Could Wells have misunderstood the purpose of the Nüsslein-Volhard & Wieschaus experiment? No, Wells may be an IDiot but he's not that stupid. When Wells makes an issue of the fact that Nüsslein-Volhard & Wieschaus did not find any beneficial mutations there's only one rational conclusion: Wells was deliberately misrepresenting the truth.

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[Photo Credit: Jonathan Wells from Conservapedia]

Way to Heaven

 
This woman was greeting people at the subway stop outside of the Pharmacy Building on the university campus. You don't see this very much aroound here so I thought I take a picture.

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Parliament

 
I was cleaning up the photos on my cellphone and I found this. The buildings in the background are Canada's Parliament Buildings on "the hill." It's where all the MP's elected on Tuesday will be meeting in a few weeks. Does anyone recognize where I was when I took the picture?

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Tangled Bank #116

 
The latest issue of Tangled Bank has been published on Pro-Science [116th Tangled Bank].

Welcome to the 116th edition of the Tangled Bank. As usually, we have a lot of good stuff for you all. Unlike some former hosts, I am not a very creative writer, and I'll spare you all from any attempts of making some kind of theme for this Tangled Bank. So, without any further ado, let's get to the posts.

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Send an email message to host@tangledbank.net if you want to submit an article to Tangled Bank. Be sure to include the words "Tangled Bank" in the subject line. Remember that this carnival only accepts one submission per week from each blogger.

Balancer Chromosomes

Monday's Molecule #92 was a depiction of an inversion in a Drosophila chromosome (right).

The chromosomes shown here are the large polytene chromosomes of the salivary glands. They are made up of 1000-2000 aligned stands of DNA that form when successive rounds of DNA replication are not followed by separation of cell division. Flies that are heterozygous for a wild type chromosome and one with a large deletion inversion, will form the loop structure shown in the diagram.

In normal cells, you won't see this structure as the chromosomes align during mitosis and meiosis, but it still exists. What the structure tells us is that the presence of an inversion, or any other type of chromosomal rearrangement for that matter, doesn't have much effect on chromosomal alignment and segregation during cell division.

Today we want to focus on another point. Imagine that a recombination event (crossover) occurs when the chromosomes are aligned like this. If the crossover takes place in the inverted region then each of the recombined chromosomes will be missing some genes and the cells that are produced from such an event will die.

Imagine that the crossover occurs between point C and D. If we trace the new chromosome staring from A on the black chromosome (the AR chromosome) then you get A B G F E D on the black chromosome followed by C B A on the normal white chromosome. The other product of the crossover will begin with A B C from the normal white chromosome and end with D E F G B A from the black homologue.

There won't be any viable crossovers in the region covered by the mutation. We will see what this has to do with balancer chromosomes in a minute.

Imagine that you are working with an important mutation (x) that affects embryonic development in Drosophila. Flies that are homozygous for the mutation (x/x) are blocked at a particular stage of development and the visible phenotype of the mutations tells you a great deal about the genes that control development. These mutations are recessive lethals. The heterozygous flies with one mutant chrmosomes and one normal chromosome (x/+) are viable.

You want to maintain a stock of these flies so you can have mutant flies whenever you need to do an experiment. If you put a heterozygous male and female together in a fly bottle and leave them for a few weeks, you won't be surprised to find that there are no flies that are homozygous for the lethal mutation. However, repeated crossings of heterozygotes will result in 25% wild-type flies (+/+) and these flies will continue to mate with each other and with the heterozygous flies. You won't be able to tell which flies carry your valuable mutation.

One way around this is to mark your mutant chromosomes with a visible marker. Let's say that your mutation is on chromosome 2. (There are three autosomes and one pair of sex chromosomes in Drosophila.) You will need a dominant marker for reasons that will soon become apparent so let's choose detached (Dt), a mutation that effects the vein pattern on the wings. The chromosome carrying your valuable developmental mutation (x) will also carry the Dt allele.

Now all you have to do is look in your stock bottle for flies with the detached phenotype and you know that those flies should be heterozygous for x (Dt x/+ +). Flies that have normal wings can be recognized and killed. (Drosophila genetics is the ultimate blood sport.)

Problem solved, right?

No. It won't be long before a recombination event separates Dt and x, especially if they are far apart on chromosome 2. After a while you still won't know which flies carry your valuable mutation.

This is where balancers come in handy.

Let's look at the experiment done by Christiane Nüsslein-Volhard and Eric Wieschaus in the late 1970's. This is the experiment that won them the Nobel Prize.

In one of their experiments they were looking for mutations on chromosome 2 that affected embryo development.

They started with a line of flies that had eye color markers on chromosome 2; cinnabar (cn) and (bw). This is the red chromosome in the diagram. They treated males from this line with the potent mutagen ethyl methanesulfonate (EMS) and crossed them to a strain carrying a balancer chromosome (black) and a non-balancer homologous chromosome (blue).

The balancer chromosome is called CyO and it has several interesting features. First, it has a large inversion called In(2LR)O that covers most of the chromosome leaving only the ends intact. Second, it carries a dominant mutation called Curly (Cu) that produces flies with curly wings. This is a homozygous lethal mutation. Third, it carries another homozygous lethal mutation called dumpy-lethal (dp^1vI). Finally it carries cn. (Also purple (pr).)

The blue chromosome carries an allele called DTS-91. DTS stands for dominant temperature sensitive. Flies that carry even a single copy of this alleles will die at high temperature. DTS also stand for David T. Suzuki, the man who created these alleles but that's just a coincidence.

The first cross is done at high temperature. The flies produced from the first cross are the F1 generation. None of them will carry the blue chromosome because those flies will be killed at high temperature. All of them will carry one mutagenized chromosome 2 and the CyO balancer chromosome. These flies are crossed again with DTS-91/CyO flies at high temperature to get the second generation (F2) of flies that all contain one mutagenized chromosome 2 and CyO. The second cross helps eliminate other mutagenized chromsomes so that the workers will only be looking at mutations that affect chromosome 2.

Now the cn x bw/CyO flies are allowed to mate with each other until it's time to look at the effect of the mutations. The stock will never produce homozygous cn bw flies as long as the mutated chromosome carries a recessive lethal. Stocks that have flies with cinnibar eyes and not curly wings are discarded.

The stock will never produce flies that are homozygous for the balancer chromosome since it carries two recessive lethal mutations. All flies will have curly wings because they carry the balancer chromosome with Cu. There will never be a recombination event that transfers the developmental mutation to the balancer because the balancer contains a large deletion inversion.

This is why balancer chromosomes are so important n Drosophila genetics. They are essential for maintaining fly stocks carrying homozygous lethal mutations. Such mutations have been extremely important in sorting out fly development.

Christiane Nüsslein-Volhard and Eric Wieschaus created thousands of lines carrying recessive lethal mutations on chromosome 2, and thousands on the X chromosome and chromosome 3, each of which have their own balancers. Then they examined each line to look for embryos that were blocked during early development. (25% of the eggs will be homozygous for the mutant chromosome.)

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[Lower Figure credit: St Johnston (2002)]

St. Johnston, D. (2002) THE ART AND DESIGN OF
GENETIC SCREENS: DROSOPHILA MELANOGASTERNature Reviews: Genetics 3:178-188. [PDF]

Nobel Laureates: Christiane Nüsslein-Volhard and Eric Wieschaus

 

The Nobel Prize in Physiology or Medicine 1995.

"for their discoveries concerning the genetic control of early embryonic development"

Christiane Nüsslein-Volhard (1942 - ) and Eric F. Wieschaus (1947 - ) received the Nobel Prize in Physiology or Medicine for their contribution to understanding the genetics of development in the fruit fly, Drosophila melanogaster.

Their main contribution was to identify a number of genes that controlled the development of the embryo. The approach was to create mutations at random then screen large numbers of flies for recessive lethals affecting various stages of early embryogenesis. The initial large scale experiment was carried out at the EMBL Labs in Heidleberg, Germany. They established 27,000 lines containing mutated chromosomes and characterized 139 mutations affecting embryogenesis. Of these, 15 were described in the classic 1980 Nature paper. (See Silver Screen, a tribute to the paper on it's 25th anniversary.)

The original 15 genes were: cubitus interruptus, wingless, gooseberry, hedgehog, fused, patch, paired, even-skipped, odd-skipped, barrel, runt, engrailed, Kruppel, knirps, and hunchback. To anyone familiar with the field this reads like a who's who of Drosophila development. Dozens (hundreds?) of papers have been published on each of these genes.

The experimental approach is described in the Press Release below. I am only including the part that refers to Nüsslein-Volhard and Wieschaus. They shared the prize with Edward Lewis.

THEME:
Nobel Laureates

Brave decision by two young scientists

Christiane Nüsslein-Volhard and Eric Wieschaus both finished their basic scientific training at the end of the seventies. They were offered their first independent research positions at the European Molecular Biology Laboratory (EMBL) in Heidelberg. They knew each other before they arrived in Heidelberg because of their common interest: they both wanted to find out how the newly fertilized Drosophila egg developed into a segmented embryo. The reason they chose the fruit fly is that embryonic development is very fast. Within 9 days from fertilization the egg develops into an embryo, then a larvae and then into a complete fly.

Fig. 1 Regions of activity in the embryo for the genes belonging to the gap, pair-rule, and segment-polarity groups. The gap genes start to act in the very early embryo (A) to specify an initial segmentation (B). The pair-rule genes specify the 14 final segments (C) of the embryo under the influence of the gap genes. These segments later acquire a head-to-tail polarity due to the segment polarity genes.

They decided to join forces to identify the genes which control the early phase of this process. It was a brave decision by two young scientists at the beginning of their scientific careers. Nobody before had done anything similar and the chances of success were very uncertain. For one, the number of genes involved might be very great. But they got started. Their experimental strategy was unique and well planned. They treated flies with mutagenic substances so as to damage (mutate) approximately half of the Drosophila genes at random (saturation mutagenesis). They then studied genes which, if mutated would cause disturbances in the formation of a body axis or in the segmentation pattern. Using a microscope where two persons could simultaneously examine the same embryo they analyzed and classified a large number of malformations caused by mutations in genes controlling early embryonic development. For more than a year the two scientists sat opposite each other examining Drosophila embryos resulting from genetic crosses of mutant Drosophila strains. They were able to identify 15 different genes which, if mutated, would cause defects in segmentation. The genes could be classified with respect to the order in which they were important during development and how mutations affected segmentation. Gap genes (Fig 1) control the body plan along the head-tail axis. Loss of gap gene function results in a reduced number of body segments. Pair rule genes affect every second body segment: loss of a gene known as "even-skipped" results in an embryo consisting only of odd numbered segments. A third class of genes called segment polarity genes affect the head-to-tail polarity of individual segments.

The results of Nüsslein-Volhard and Wieschaus were first published in the English scientific journal Nature during the fall of 1980. They received a lot of attention among developmental biologists and for several reasons. The strategy used by the two young scientists was novel. It established that genes controlling development could be systematically identified. The number of genes involved was limited and they could be classified into specific functional groups. This encouraged a number of other scientists to look for developmental genes in other species. In a fairly short time it was possible to show that similar or identical genes existed also in higher organisms and in man. It has also been demonstrated that they perform similar functions during development.

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[Photo Credits: Nüsslein-Volhard - Encylopaedia Britanica, © Patrick Piel/Gamma Liaison, Wieschaus -News at Princeton]

Fair Vote Canada Election Results

 
Here's what the result would have been with a nation-wide proportional system from Fair Vote Canada.

Conservatives - 38% of the popular vote: 117 seats (not 143)
Liberals - 26% of the popular vote: 81 seats (not 76)
NDP - 18% of the popular vote: 57 seats (not 37)
Bloc - 10% of the popular vote: 28 seats (not 50)
Greens - 7% of the popular vote: 23 seats (not 0)

I don't favor such a system. I like the Mixed Member Proportional MMP) system based on provinces.

The British Columbia referendum on the Single Transferable Vote (STV) system for provincial elections is set for May 12, 2009. 58% of voters supported the new voting system in the last referendum (2005). This was just short of the required 60%. It is very likely that the new proportional system will be adopted this time around, making British Columbia the first of many provinces to enter the 21st century.

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Nigeria Has Competition

 
I just got this email message and I thought I'd share it with the rest of you. All my money is tied up in deals with Nigerians and investments in Viagra so I can't take advantage of this fabulous offer.

I expect to be flush with cash by next week because I just won the European lottery but I'll be spending most of it to enlarge one of my vital organs.

Hello Pal,

I hope my email fine you well. I am in need of your assistance. My name is Sgt. Jarvis Reeves. I am an American soldier serving in the 1st Armored Division in Iraq, we have just been posted out of Iraq and to return in a short while. My colleague and I need your help to transfer out the sum of Twenty Five Mllion U.S Dollars ($25 MUSD). If you are interested I will furnish you with more details

As awair your response.
Email:sgt.jr@hotmail.com

Yours,
Sgt. Jarvis Reeves

God Bless America!!

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Move to Canada

 

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[Hat Tip: The Unexamined Life]

Bacteria Phylogeny: Facing Up to the Problems

There are millions of species of bacteria. Sorting out their evolutionary history has been a major challenge for decades. Unlike the much bigger, multicellular, eukaryotes, there are few morphological markers to assist scientists in classifying bacteria. The fossil record is mostly silent.

Molecular evolution came to the rescue thirty years ago when cloning and sequencing became common. Soon there were elaborate and detailed phylogenetic trees based on comparing sequences of conserved genes from many species.

The gene of choice was the one for the small subunit ribosomal RNA (SSU rRNA). This gene was well conserved in bacteria and it was easy to get sequences simply by PCR. (The ends of the SSU rRNA gene are conserved and this means that you can develop universe primers for PCR.)

Over the years, the SSU rRNA gene has become what is called the "gold standard" in bacterial phylogeny and taxonomy. Many species have been assigned to taxa based entirely on the sequence of their SSU rRNA gene. Unfortunately, the "gold standard" has become somewhat tarnished lately.

Our fellow blogger, Jonathan Eisen of The Tree of Life, has recently published a paper that looks at the problems with bacterial phylogeny (Wu and Eisen, 2008). He posted a brief summary of the paper and commented on why he likes the journal Genome Biology [Happy Open Access Day: Back to Genome Biology for Me].

There is much to like about this paper. The authors face up to the problems with the current bacterial phylogeny, which is based almost entirely on a single gene (SSU rRNA). They point out that this is risky given what we know about molecular phylogenies. Furthermore, in the case of the SSU ribosomal RNA gene we know for a fact that this has led to problems and inconsistencies. In addition to the practical difficulties there are good theoretical reasons for being suspicious of phylogenies constructed from nucleotide sequences.

What to do? One possible solution is to abandon SSU rRNA as a "gold standard" and replace it with a highly conserved protein coding gene. Unfortunately, this doesn't get around the problem of relying on a single gene. The way around this is to use an artificial concatenated sequence made up of several different conserved genes laid out end-to-end in one large string of amino acids.

So why isn't this done? Because, as Wu and Eisen point out, it ain't that easy. The main difficulty in any phylogenetic study is getting a proper alignment. This is a problem that many workers simply ignore when they use automated alignment software like CLUSTALW. These workers assume that the alignments are valid.

They aren't, and this is another example of facing up to the problem. Many scientists agonize over what program to use when constructing their trees—should they use maximum likelihood, parsimony, etc. etc.? In most cases these decisions are a complete waste of time because their alignments aren't good enough to make a difference.

Here's how Wu and Eisen explain it ...

It has been shown that alignment quality can have greater impact on the final tree than does the tree-building method employed [20]. Therefore, preparing high quality sequence alignments is a most critical part of any molecular phylogenetic analysis. This preparation typically involves careful but tedious manual editing and trimming of the generated alignments, and thus remains the biggest challenge to automation. When scaling up this process, the trimming step is often simply ignored. Automated trimming based on the number of gaps in each column or each column's conservation score can be used to select conserved blocks, but still is not satisfactory when a high quality tree is required.

Keep in mind that what is being proposed is a large tree based on concatenated sequences from many genes. You don't want to do multiple sequence alignments for every gene by hand, and yet up until now, that was the only way to get accurate results.

Wu and Eisen have written a program called AMPHORA that hopefully solves this problem. They begin by manually creating "seed alignments" that are manually curated. Then they use AMPHORA to align all the other sequences to the seed alignments. In this way they hope to overcome the limitations of automated multisequence alignment without having to align everything by hand.

None of this would be possible, of course, unless there were large numbers of species where every one of the target genes have been cloned and sequenced. In the 20th century this would have been impossible but now there are hundreds of completely sequenced bacterial genomes. This means that each one of them has a sequenced copy of the genes required for this kind of analysis.

All that's left is to identify the completely sequenced genomes and pick the set of genes. There are 578 genomes in the database but many of these are close relatives that will not be useful in constructing a large tree of all bacterial sequences. The final set contains 310 genomes with representatives of all the major groups.

The authors selected 31 genes for their initial proof of principle paper (dnaG, frr, infC, nusA, pgk, pyrG, rplA, rplB, rplC, rplD, rplE, rplF, rplK, rplL, rplM, rplN, rplP, rplS, rplT, rpmA, rpoB, rpsB, rpsC, rpsE, rpsI, rpsJ, rpsK, rpsM, rpsS, smpB, tsf). Those of you who recognize these genes will see that 21 of them are small ribosomal proteins. This was not the best choice, in my opinion, but the authors of the paper note that they are continuing the study by incorporating better genes such as HSP70 (dnaL) and EF-Tu (tufA). You can't just choose any conserved gene because it has to be present in most species and there are surprisingly few genes that meet that criterion.

After all that, what's the bottom line? The grand phylogeny is shown at the top of this posting. It resolves many groups that are unresolvable using the SSU rRNA tree. In some cases this tree reveals species that have been incorrectly assigned to higher taxa. These species will have to be reclassified if this result holds up.

The most important finding is that the method works and it yields trees with excellent resolution of the major bacterial taxa.

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Wu, Martin, Eisen, Jonathan (2008). A simple, fast, and accurate method of phylogenomic inference Genome Biology, 9:R151 [Genome Biology] [doi:10.1186/gb-2008-9-10-r151]