Thursday, October 30, 2008

Proposition 8

 
Last May the California Supreme Court ruled that same-sex couples have the right to marry according to the California Constitution. Since then 16,000 same-sex couples have been married in California [California Proposition 8 (2008)].

On November 4th voters will decide on whether or not to change the California Constitution to block the marriage of same-sex partners. This is Proposition 8:
ELIMINATES RIGHT OF SAME-SEX COUPLES TO MARRY. INITIATIVE CONSTITUTIONAL AMENDMENT. Changes the California Constitution to eliminate the right of same-sex couples to marry in California. Provides that only marriage between a man and a woman is valid or recognized in California. Fiscal Impact: Over next few years, potential revenue loss, mainly sales taxes, totaling in the several tens of millions of dollars, to state and local governments. In the long run, likely little fiscal impact on state and local governments.
The latest polls indicate that the "yes" side has a slight lead. If the "yes" side wins next Tuesday, it will be illegal for same-sex couples to marry in California.

This is California, folks. In the United States of America. In the 21st century. Gay couples are getting married but that right might be withdrawn.

What the heck is going on?


[Photo Credit: BBC News]

Tangled Bank #117

 
The latest issue of Tangled Bank has been published on Pro-Science [Tangled Bank #117].
Welcome everybody to the 117th edition of the blogosphere’s premiere science and medicine blogcarnival, Tangled Bank. Tangled Bank started out as a sort of Carnival of the Vanities for science bloggers taking it’s name from Charles Darwin’s famous metaphor:
It is interesting to contemplate a tangled bank, clothed with many plants of many kinds, with birds singing on the bushes, with various insects flitting about, and with worms crawling through the damp earth, and to reflect that these elaborately constructed forms, so different from each other, and dependent upon each other in so complex a manner, have all been produced by laws acting around us. These laws, taken in the largest sense, being Growth with Reproduction; Inheritance which is almost implied by reproduction; Variability from the indirect and direct action of the conditions of life and from use and disuse: a Ratio of Increase so high as to lead to a Struggle for Life, and as a consequence to Natural Selection, entailing Divergence of Character and the Extinction of less-improved forms.
It’s fitting that this edition should itself present such a tangled bank of blog posts intertwining many different fields of science and medicine. Unfortunately, that means it becomes almost impossible to find a common theme or even group together the posts in any meaningful way. So I’m going to take the easy way out and simply list them in no particular order, although we’ll try to group related posts together.


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.

The Best Invention of 2008

 
According to Time magazine it's "The DNA Retail Test." Especially the one marketed by 23andMe.
We are at the beginning of a personal-genomics revolution that will transform not only how we take care of ourselves but also what we mean by personal information. In the past, only élite researchers had access to their genetic fingerprints, but now personal genotyping is available to anyone who orders the service online and mails in a spit sample. Not everything about how this information will be used is clear yet — 23andMe has stirred up debate about issues ranging from how meaningful the results are to how to prevent genetic discrimination — but the curtain has been pulled back, and it can never be closed again. And so for pioneering retail genomics, 23andMe's DNA-testing service is Time's 2008 Invention of the Year.
  1. It's not an invention. The technology has been in place for years. It depends on the work done by hundreds of labs who are investigating the human genome. They deposit their results in public databases.

  2. The profit making company is emphasizing genealogy as much as health. For $1000 (now $399) you can find out how your haplotyes compare to others. This is the best invention of 2008?

  3. There are serious ethical concerns about genetic testing that have not been resolved.

  4. Other companies are selling tests that are just as good and The Genographic Project from National Geographic deserves just as much, if not more, credit than any private company.

  5. Many of the people who buy these products are scientifically literate, and responsible, adults. But there's plenty of opportunity to exploit others who might not understand what the test means.


What the Heck Is This?

 
You must go to Botany Photo of the Day to find out. Be thankful that we can't reproduce smells on our blogs.




32 Nearby Stars

 
Check out this interactive star map of the 32 nearest stars [32 Nearby Stars].

Imagine that humans could establish colonies on several of these stars in the next 10,000 years. This means that we would have reached out 10 light years in that time. Continuing at that pace, in one million years we would have colonies that are 1000 light years away. In one hundred million years we will have covered more than half the galaxy.

If there are other civilizations like ours, they would have to be less than one hundred million years older than us or they would likely be here by now. Maybe we are alone in the galaxy/universe?

UPDATE: I've been reminded that this argument against the high probability of life is known as the Fermi Paradox.


[Hat Tip: Bad Astronomy]

On Assuming that God Obeys the Laws of Physics and Chemstry

 
John Pieret admires a recent posting by Steven Novella on NeuroLogica Blog where he (Novella) writes about More on Methodological Naturalism.
This methodoligical approach also deals with the problem of whether or not science can deal with God. The answer is - yes and no. If a supernatural (meaning inaccessible to science) power were meddling with our universe (with stuff science could access), science could detect it, document it, and even describe it. We could say that something was happening.

However (by the premises of this hypothetical situation) if the ultimate cause of these physical effects were beyond scientific methodology, the best science could do would be to describe anomalies. Science comes across anomalies all the time, and the typical approach is to assume (because we really have no choice) that the anomalies are due to either errors in observation, errors in our current theories, or incompleteness in our current theories, meaning there is some new phenomenon to discover.

So far the scientific approach (assuming anomalies will lead to a deeper understanding of reality) has worked out pretty well. This is the best evidence we have that our universe if mostly rational and does not include “supernatural” (by my definition) forces that will remain forever “mysterious.” If it did, then we would run across anomalies that we could never explain scientifically. All we could do would be to describe them, but we could never come up with a testable theory of mechanism.
I pretty much agree with what Steven Novella says here, although I note that he gets a bit fuzzy in other parts of the same posting. The basic point is that scientists are capable of detecting things that are not explainable by naturalistic explanations. In other words, if something isn't obeying the laws of physics and chemistry,1 then we''ll know about it, even if we have to put it down as an unexplained anomaly.

The fact that there aren't any known mysteries that fall into this category means that there is no evidence for a God that acts in a supernatural manner. This is not the God of Francis Collins. Collins is a scientist who presents "evidence" that God exists.

The fact that most other scientists do not find such evidence is not proof that all types of God don't exist. It merely defines limits to the types of God that are possible if you use scientific reasoning.

John Pieret seems to knows this since in his posting Natural Method he asks:
I would quibble that divine action would not necessarily produce anomalies. For example, how could we tell the difference between a random mutation and a miraculous one?

Claiming that we can see no pattern in mutations, or the evolution it powers, does no good because that requires that you make an assertion about what God wants to do and how he, she or it would go about it -- and how could you know that?
John is doing exactly what he says is wrong. In light of the fact that several testable hypotheses about God have been refuted, John then speculates about what God might be doing to get around the conflict between science and religion. He imagines that God could, if he so wished, disguise his actions so that they were indistinguishable from actions that were entirely natural.

None of us can refute that possibility but I note that the goalposts have moved just about as far as they can go. We're left with a God who is so careful to avoid revealing himself that he might as well not exist. What's the point?

Why in the world did anyone start believing in such a God in the first place?2

If we weren't talking about religion, this kind of "logic" would be quickly dismissed. Imagine, for example, that someone claimed the stock market was being manipulated by clever gremlins. Pointing out that there was no evidence of such manipulation provokes the response, "These are very clever gremlins who go to extraordinary lengths to disguise their manipulations. That's why we can't detect them."

Since we can't disprove the existence of such gremlins, is that a reason to believe in them? Should we treat the gremlin-believers in the same way that we treat everyone else or are we right to be a little concerned about their psychological well-being? Is it okay to tentatively conclude that they are deluded?

Why does belief in God always get special privileges that we never grant to any other superstitions?


1. It's a metaphor, John, not the be taken literally.

2. The answer, of course, is that nobody ever believed in such a God. This sort of God is merely the last refuge of those who used to believe in a personal, interventionist God but now find that they can't defend such a belief in a modern skeptical society. It's also the fallback position for those strange people who call themselves true agnostics. They have almost as much at stake in trying to show that we can't "prove" the nonexistence of God. They desperately want to avoid being a non-believer (atheist).

Citing Blogs

 
Some of my students have been asking how to cite blogs and other internet sources. I found a set of instructions on the NCBI website and I thought Id share them with you [26. Electronic Mail and Discussion Forums].

According to those instructions, you should cite Pharyngula like this:
Myers PZ (University of Minnesota, Morris, MN). Pharyngula [blog on the Internet]. New York: ScienceBlogs LLC. [2006 Jan] - [cited 2007 May 16]. Available from: http://scienceblogs.com/pharyngula/.
I'm not sure I agree with everything that's there. For example, I don't think it's useful to have the date when the blog started (2006, Jan). I don't think we need the affiliation of the author, or where the blog is published—unless it's part of a collective. I think it's important to cite a specific posting if that's what you're referring to.

Here's how I would cite today's posting on worshiping golden cows.
Myers, P.Z. (2008) Pharyngula [Internet blog] - "Where's Charlton Heston when you need him?" (Oct. 29, 2008) [cited Oct. 30, 2008]. ScienceBlogs LLC, New York. Available from: http://scienceblogs.com/pharyngula/2008/10/wheres_charlton_heston_when_yo.php
Here are some examples of how to cite comments on blogs [Examples of Citations to Blogs]. In the first example the author is unknown. In the second example the comment author is identified by affiliation.
Teresa. Comment on: "Flo's pledge: deal or no deal?" 2007 May 12 [cited 2007 May 16]. In: Kim. Emergiblog: The Life & Times of an ER Nurse [Internet]. San Francisco: Emergiblog. c2005-2007 - . [about 1 screen]. Available from: http://www.emergiblog.com/2007/05/flos-pledge-deal-or-no-deal.html scroll down to comments.

Lanard J (Western Pacific Regional Office of the World Health Organization, Manila, Philippines). Comment on: "This blog can save your life!" and "Health Communication: Science and Art." 2006 Oct 15 [cited 2007 May 17]. In: Bernhardt JM. Director's Blog [Internet]. Atlanta: Centers for Disease Control and Prevention (US), National Center for Health Marketing. [2006 Jul 13] - . [about 2 screens]. Available from: http://www.cdc.gov/healthmarketing/blog_101106.htm scroll down to locate comment.


Wednesday, October 29, 2008

The Meat-Robots Are Stirring

 
The mind-body problem is one of the more serious problems in philosophy. At the risk of over-simplifying, the two main camps can be described as dualism and monism. A dualist thinks that there's more to the mind than just neurons—the word that comes up most often is consciousness. The monist rejects the idea that there is some vitalist component to the mind. It can all be explained by the structure of the brain and the laws of physics and chemistry.

Monists are materialists, for the most part. Dualists often believe in supernatural beings.

Michael Egnor writes articles on Intelligent Design Creationism for the Evolution News & Views website at the Discovery Institute. He thinks the materialists have been winning but it's time for the zombies meat-robots to strike back.

As a general anti-science strategy, it's easy to see why the mind-body problem is resurfacing. The IDiots have lost the battle over evolution so they have to look around for something else to attack. We (scientists) don't understand exactly how the mind works. That's a perfect gap to shove God into, for now.
The materialist project to explain the mind reads less like a compendium of scientific and philosophical investigation than like a psychiatrist’s case log. Succinctly, the materialist project is batsh*t. The mind is a catastrophe for materialism. Materialism doesn’t explain the mind, and it probably can’t explain the mind. Materialism flounders on the hard problem of consciousness — the problem of understanding how it is that we are subjects and not just objects. Now a number of scientists and other academics are challenging this repellent materialist nonsense. There’s no scientific or even logical justification for the inference that the mind is merely the brain, without remainder, and the philosophical and sociological implications of the materialist view of the mind are abhorrent. Now there’s a reality-based push-back to materialist superstition, and the materialists have an insurrection on their hands.

The meat-robots are stirring.
I wonder if the meat-robots have something substantial to contribute to the discussion or whether they'll just be complaining about science, as they always do?


Voting Machines

 
We just had a Federal Election in Canada. We used paper ballots and the results were in by midnight. I had only one choice to make.

This isn't possible in the USA because American vote for many different candidates when they have an election. The ballots can be very complicated but you can always vote "straight Republican" or "straight Democrat" to simplify the process. Here's how voting machines work .... or not.




[Hat Tip: Mike the Mad Biologist]

Nobel Laureate: Albrecht Kossel

 

The Nobel Prize in Physiology or Medicine 1910.
"in recognition of the contributions to our knowledge of cell chemistry made through his work on proteins, including the nucleic substances"

Albrecht Kossel (1853 - 1927) won the Noble Prize for his studies on proteins, especially those proteins that bind to nucleic acids. He was the first to characterize protamines and histones.

The significance of Kossel's work was not fully appreciated because at the time proteins were thought to be the information carrying molecules and nucleic acids were merely structural components of the nucleus. One gets the impression that the simplicity of the protamines, and to a lesser extent, the histones, was a disappointment.

The flavor of thinking in 1910 is captured by the presentation speech on the Nobel rize website.

THEME:
Nobel Laureates
There are several kinds of proteins. One group which is included here are the so-called protamines obtained from the milt of fish. Kossel has made a detailed study of these. For these a relatively simple structure has been discovered inasmuch as the number of dissimilar atom groups in them is not very great. They therefore present simpler relationships than proteins in general, and consist mainly of substances belonging to the group which I have just called basic breakdown products of protein. For certain protamines Kossel, thanks to his methods of determination, has in fact been able to establish the quantitative relationships of the building blocks making up these protamines, a goal which we seem to be far from attaining where the other proteins are concerned.

Work on these most simple protein bodies, i.e. the protamines, is however not only of great importance because it has explained the structure of such protein bodies. The protamines are also of direct interest for the knowledge of certain cells and their life, because they are in fact characteristic of certain transformation products of the cells and are formed from ordinary protein.

One protein group, first observed by Kossel, consists of the so-called histones. They stand between the protamines and what is termed ordinary protein. This group, again, is important because of its occurrence as a component of certain cells, and has also been studied in detail by Kossel.

Professor Kossel has made an extensive and important study of the problem of the protein compounds in cells. As we have already mentioned, the proteins are very complex bodies. Within the cells the relationships are further complicated by the fact that the proteins there are combined in varying degrees with other substances such as those grouped under the name of «nucleic acids.
It is clear from Kossel's Nobel Lecture that he recognized the importance of chromatin in heredity but was unclear about which component corresponded to genes.
If we now summarize the results of the investigations of loosely bound nuclein substances, the result is a follows: A composition of the chromatin substance of the cell nucleus from two components, the one rich in bound phosphoric acid and having the qualities of an acid; the second showing a protein with the qualities of a base. In their chemical structure both components show a notable similarity based on the remarkable accumulation of nitrogen atoms and because of this chemical structure the chromatin formations can be sharply differentiated from the remaining cell components; and this quality must obviously be associated with the function of the chromatin substances. These atom groups rich in nitrogen and containing phosphorus are those whose deposits in the chromosomes are first set in motion during cell division and whose transmission to other cells forms an essential part of the reproductive process.


Tuesday, October 28, 2008

Translation at CSH

 
My co-author, Marc Perry, is at the Cold Spring Harbor Laboratories on Long Island (NY, USA). He sent me this photograph. I think it may be a Henry Moore.





This Book Don't Need Reviews

 
Book Description (from Dembski at Uncommon Descent):
Although atheism might have been logically tenable before Darwin, writes Richard Dawkins, Darwin made it possible to be an intellectually fulfilled atheist. This little book shows that atheism must seek intellectual fulfillment elsewhere decisively demonstrating the need for intelligence in explaining life’s origin. This is the best overview of why traditional origin-of-life research has crashed and burned and why intelligent design is necessary to explain the high-tech engineering inside the cell.

Author William A. Dembski worked closely as an advisor with the producers of the Spring 2008 documentary Expelled: No Intelligence Allowed starring Ben Stein. How to Be an Intellectually Fulfilled Atheist (Or Not) is the intellectual argument that helped inform significant elements of the movie. This controversial feature-length documentary film about researchers, professors, and academics who claim to have been marginalized, silenced, or threatened with academic expulsion because of their challenges to some or all parts of Darwin’s theory of evolution is one of the top twelve highest grossing documentary’s of all time. It has attracted both praise and controversy in its challenge against Darwinism.
If you liked the previous books by Jonathan Wells and William Dembski then you'll love this one. If you didn't, then you won't.

Did he really say "Ben Stein" and "intellectual argument" in the same sentence?


Junk DNA Opponents Are at It Again

 
Nils Reinton has just posted a provocative piece on Sciphu entitled Hammering nails in the “junk-DNA” coffin. Here's what he says,
Below you will find a list of references that I hope will contribute to the fall of the term “junk-DNA“, - some of it may (currently) lack a known function, but it is not junk !!!

Disclaimer: This is a list of useful references when arguing against the common overestimation of the amount of “junk”-DNA. By listing these I am not claiming anything beyond what I have already posted on this blog or in a comment somewhere. Also and importantly, I have not myself had the time to review these articles as thoroughly as I would have wanted to, - some have been read carefully, others lightly and yet others just skimmed through. Thus, you are more than welcome to comment on these references if you have opinions on any of them, or find them unsuited for this list.
You are more than welcome to visit Sciphu and make comments. I can't be bothered.

The articles are just the same-old, same-old, litany of occasional discoveries of functional bits of DNA coupled with a fanatical belief in the biological significance of every single transcript that has ever been reported in the literature.

Oh yes, I almost forgot. Nils also throws in some papers about the number of binding sites for transcription factors. I guess he hasn't read any of my postings on the importance of non-specific binding [see Transcription Factors Bind Thousands of Active and Inactive Regions in the Drosophila Blastoderm].

THEME

Genomes & Junk DNA

Total Junk so far

    54%
I think there's good reason to assume that up to 90% of our genomes consist of junk DNA where the word "junk" means that it does not have a biological function. I haven't been able to keep up my series of postings analyzing the human genome but so far there's very good reason to believe that more than half is junk.

I've never seen an anti-junkie address the genetic load argument. Has anyone else? I wonder how they think we can survive if a substantial amount of our DNA is essential?


Schizophyllum commune Has 28,000 Distinct Sexes

 
This is the Botany Photo of the Day from The University of British Columbia Botanical Garden and Centre for Plant Research. The organism is the fungus Schizophyllum commune which is reported to have 28,000 sexes according to Tom Volk's Fungus of the Month for February 2000. Check out the Botany Photo of the Day blog for a much better picture.

In some parts of the world sex is legally restricted to arrangements involving single members of specified gender. I wonder which sexes of Schizophyllum commune would qualify? Personally, I think that members of sex 408 should be allowed to marry members of sex 12,105 but all other marriages are immoral and should be illegal.





Definitions Matter: Negative Selection and Postive Selection

 
In recent issues of the Proceedings of the National Academy of Sciences (USA) we have an interesting example of misuse of a key term in evolution.

The paper in question is by Sun et al. (2008a) of the University of California, San Francisco. The title of the paper is important: "Experimental evidence for negative selection in the evolution of a Yersinia pestis pseudogene." Here's how they describe this negative selection in the abstract,
Yersinia pestis, the agent of bubonic plague, evolved from the enteric pathogen Yersinia pseudotuberculosis within the past 20,000 years. Because ancestor and descendant both exist, it is possible to infer steps in molecular evolution by direct experimental approaches. The Y. pestis life cycle includes establishment of a biofilm within its vector, the flea. Although Y. pseudotuberculosis makes biofilms in other environments, it fails to do so in the insect. We show that rcsA, a negative regulator of biofilms that is functional in Y. pseudotuberculosis, is a pseudogene in Y. pestis. Replacement of the pseudogene with the functional Y. pseudotuberculosis rcsA allele strongly represses biofilm formation and essentially abolishes flea biofilms. The conversion of rcsA to a pseudogene during Y. pestis evolution, therefore, was a case of negative selection rather than neutral genetic drift.
Hmmm ... something about this form of "negative selection" seems puzzling. Does anyone see what it is?

The article was published online on June 3, 2008 and appeared in the June 10, 2008 issue of PNAS. It was communicated by National Academy member Stanley Falkow of Stanford University.

In this week's issue (Oct. 21, 2008) we see a letter from Jianzhi Zhang of the Department of Ecology and Evolutionary Biology, University of Michigan (Zhang, 2008).
There are two types of natural selection in biological evolution: Positive (Darwinian) selection promotes the spread of beneficial alleles, and negative (or purifying) selection hinders the spread of deleterious alleles (1). Pseudogenization is normally detrimental and prevented by negative selection. However, changes in genetic background or environment may render a formerly useful gene worthless, leading to the relaxation of the negative selection. Consequently, mutations disrupting the gene are fixed by genetic drift, and the gene becomes a pseudogene. This is the common type of pseudogenization by neutral evolution. Sometimes, however, a previously useful gene may become harmful to an organism. In this case, mutations destroying the gene would be beneficial and would be fixed by positive selection. Thus, pseudogenization can be adaptive (2). Recently, Sun et al. (3) reported an excellent example of adaptive pseudogenization, convincingly demonstrating that gene loss can also serve as an “engine” of evolution (4). Nevertheless, instead of calling it “positive selection,” they mistakenly used “negative selection.” The case involves Yersinia pestis, the agent of bubonic plague that is frequently transmitted by fleas. The authors found that the rcsA gene of Y. pestis became a pseudogene in the last 20,000 years (3). Replacing the rcsA pseudogene with its functional version represses the formation of biofilms in fleas (3), which would reduce the transmission rate of the bacteria. That is, the pseudogenization of rcsA allowed the formation of Y. pestis biofilms, which enhances the transmission of the bacteria, and hence was likely driven by positive selection.
That looks like a pretty devastating criticism to me. I'm convinced that the title of the paper was inaccurate. They were publishing an example of positive selection and not negative selection as claimed.

The authors replied in the same issue (Sun et al., 2008b).
In our article (1) we used “negative selection” to succinctly convey that a previously functional allele became deleterious and therefore was removed by natural selection. However, Zhang (2) is correct that our usage was contrary to the usual meaning. Olson's term, “adaptive gene loss” (3), would have been more appropriate. We are gratified that Zhang agrees with our conclusion that the pseudogenization of rcsA was adaptive.
Translation: "We really screwed up."

How did this happen? Normally, before a paper is published the work is presented at meetings and in lab group meetings. Was there nobody who recognized that the authors were using the wrong term? Clearly the authors themselves (all three) never questioned what they were putting into the title. Clearly the person who communicated the article didn't either, and neither did any of the reviewers.

What's happening to science these days? Now, don't get me wrong. These sorts of things happened in the "olden days" as well but I'm convinced that the problem is much more serious today. There is too much stuff being published that should never have made it past the lab group, let alone past reviewers.

Here's a question for everyone who has read this far. What should be done with the original paper? The title is wrong. How do we alert people to the fact that the authors have agreed that they made an error?



Sun, Y-C., Hinnebusch, J.B. and Darby, C. (2008a) Experimental evidence for negative selection in the evolution of a Yersinia pestis pseudogene. Proc. Natl. Acad. Sci. (USA) 105:8097-8101. [DOI: 10.1073/pnas.0803525105]

Sun, Y-C., Hinnebusch, J.B. and Darby, C. (2008b) Reply to Zhang: Adaptive gene loss in Yersinia pestis rcsA pseudogenization. Proc. Natl. Acad. Sci. (USA) 105:E70; published ahead of print October 15, 2008. [doi:10.1073/pnas.0807434105]

Zhang, J. (2008) Positive selection, not negative selection, in the pseudogenization of rcsA in Yersinia pestis. Proc. Natl. Acad. Sci. (USA) 105:E69; published ahead of print October 15, 2008 [doi:10.1073/pnas.0806419105]

Guns and Kids Don't Mix

 
From an Associated Press report: Boy, 8, shoots himself to death at Mass. gun show.
WESTFIELD, Mass. (AP) — With an instructor watching, an 8-year-old boy at a gun fair aimed an Uzi at a pumpkin and pulled the trigger as his dad reached for a camera.

It was his first time shooting a fully automatic machine gun, and the recoil of the weapon was too much for him. He lost control and fatally shooting himself in the head.
I'm mostly interested in the comment further down in the press release.
"This accident was truly a mystery to me," said Bizilj, director of emergency medicine at Johnson Memorial Hospital in Stafford, Conn. "This is a horrible event, a horrible travesty, and I really don't know why it happened."
Canadian Cynic says exactly what we all must be thinking.
Yeah, it's a puzzler, all right. A real stumper. Children and fully automatic weapons -- what could possibly go wrong?
This is why I love Canadian Cynic!





Monday, October 27, 2008

A Rainy Day in Toronto

 
The large white building is part of the MaRS complex of research buildings. It houses the labs of my colleagues who are based in the Hospital Research Institutes. Many of them are in my Department. I wonder if a pot of gold has appeared in one of their offices?




Gene Genie #39

 
The 39th edition of Gene Genie has been posted at Genetics & Health [Gene Genie #39: Personal genomics, health and evolution].
Welcome to the 39th edition of Gene Genie, the carnival of clinical genetics and personalized medicine.

Personalized genomics are all over the news lately, so let’s jump right and see what’s going on.
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



The Spaghetti Harvest

 
The Spaghetti Harvest in Switzerland was first broadcast by the BBC on April 1, 1957. I'm old enough to have seen it on television in 1957—it was on the The Tonight Show with Jack Parr [On This Day].



I'm not sure that you could broadcast something like this today in North America. Most people wouldn't understand. New Scientist lists it as one of Seven of the greatest scientific hoaxes.



Monday's Molecule #94

 
Most of you should recognize this molecule. You must describe both parts of the molecule, making sure to state clearly what you are seeing. As an extra challenge, you have to specifically mention something that is not shown even though it might be normally considered part of the complex.

It's a short step from there to this week's Nobel Laureate(s) but you need to be careful. There are two possible answers and one of them has already been chosen. You have to pick the other one.

The first one to correctly identify the molecule 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 three ineligible candidates for this week's reward: 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: Several people recognized that the molecule is a nucleosome. The figure on the left show the conformation of the histone core consisting of histones H2A, H2B, H3 and H4. The figure on the right shows the same protein core (rotated) with DNA wrapped around it to form the nucleosome core particle. The fifth histone, H1, is part of the linker region and it isn't shown.

Nobody guessed the Noel Laureate. It is Albrecht Kossel. There is no winner this week.


Final Notice: PZ Myers in Toronto and Guelph

 
The Center for Inquiry, Toronto and The University of Toronto Secular Alliance are sponsoring a lecture by PZ Myers this Friday evening (Halloween). Contact me if you want to meet PZ.

From the CFI press release ...

Fri, Oct 31, 2008, 7:30pm at University of Toronto, J.J.R. MacLeod Auditorium. A catered reception with PZ exclusively for Friends of the Centre will take place from 6:00 - 7:00 pm at the Centre For Inquiry.

Partnered with the University of Toronto Secular Alliance the Centre for Inquiry - Ontario presents the popular biologist and author of the stimulating blog Pharyngula. Dr. Myers is an associate professor of biology at the University of Minnesota, Morris. He obtained his B.S in zoology from the university of Washington and his Ph.D. in biology from the Institute of Neuroscience, University of Oregon. His blog is the most widely read science blog on the internet with topics ranging from octopus, religion and getting kicked out of Expelled.

Note:  On Sat, Nov 1, 2008, 2-4pm Guelph Campus Skeptics will host a more informal interactive discussion with PZ Myers at the University of Guelph, A.A. Thornbrough Building, Rm. 1200 (click THRN on the map). There will be refreshments available from 1 - 2pm. The cost is $3 and free for members of CFI.

PZ Myers Presents: Science Education: caught in the middle of the war between science and religion

Friday, October 31, 7:30 pm - 9:30 pm
MacLeod Auditorium
2158-1 King's College Circle,
Room 2158, Toronto, ON, M5S1A8
See the PZ Myers Visit website for more information, including how to get tickets and how to get to the MacLeod Auditorium.





Chris Nedin Enters the Blogosphere

 
Chris Nedin is an interrupted paleontologist who studied Ediacaran and Early Cambrian palaeontology, palaeoecology and taphonomy. He was one of the early regulars on the newsgroup talk.origins and he even came to a Howlerfest in Toronto a few years ago (1997).1 (Chris lives in Australia.)

Chris Nedin has now become a blogger. Visit Ediacaran and read his first posting: The Spandrels of San Marco and the Anomalocaris Paradigm. Here's a teaser ..

The Spandrels of San Marco and the Panglossian Paradigm is one of my favourite science papers. As someone who accepts natural selection as a powerful evolutionary mechanism, but who considers that there are other, equally, or perhaps more, powerful mechanism out there, such as genetic drift, this paper resonated a lot with me. To summarise the paper (if you haven’t read it, please do), not everything that happens in evolution occurs because it was selected for. Like spandrels, things can happen as a consequence of other events. To summarise the summary, sh*t happens.

Here I’d like to develop that theme using Anomalocarus.
Welcome to the blogosphere, Chris. With an opening like that, we expect big things in the future.


1. I still remember how excited he and Saint Andrew (Andrew MacRae) were when the curators at the Royal Ontario Museum pulled out their famous fossil of Anomalocarus to look at. Chris and Andrew, being paleontologists, were the only ones allowed to touch it. Chris was also thrilled to see the trilobites with bite marks. Read his posting to see why.

Friday, October 24, 2008

What Does Marcus Antonius Tell Us about Evolution?

 
Meet my (probably mythical)1 ancestor, Marcus Antonius (83 BC - 30 BC), better known as Mark Antony. (Color photo not available.)

Mark Antony was a friend, and cousin, of Gaius Julius Caesar, although after Caesar's assassination he stopped praising Caesar. Mark Antony had a falling out with Octavian (Augustus) after the Second Triumvirate split up and he ended up in Egypt. The history is kind of interesting but not very relevant.

We're mostly concerned about Mark Antony's genes. Near the end of his life he had three children by Cleopatra, Queen of Egypt; the twins Alexander Helios & Cleopatra Selene II and Ptolemy Philadelphus. This led to gene flow between the Italians and subpopulations in the Middle East. (There were other liaisons that contributed to gene flow in both directions between the Middle East and Europe.)

Before moving to Egypt, Mark had several wives in Rome. One of them was Octavia Major and they had a daughter, Antonia Minor. Antonia married Nero Claudius Drusus Germanicus and one of her sons was Claudius Cæsar (Tiberius Claudius Nero Germanicus), Emperor of Rome. At the time Antonia and Drusus were living in Lugdunum (Lyon, France).

Claudius married Valeria Messalina (granddaughter of Octavia) and their daughter was Genvissa (Venus Julia). Claudius then married Julia Agripina and had more children, including Emperor Nero. We aren't interested in Julia Agripina except to note her scientific contribution to the understanding of eukarotic transcription [Mushrooms for Dinner].

Genvisa married Arviragus, King of Siluria, in 45 AD. Siluria was a kingdom in the south of Wales and at the time they were resisting Roman occupation. Arviragus became King of the Britons. Their son was Meric (Marius) , King of the Britons. Do you see where this is headed?

Meric married Penardun and their son was Coel I "Old King", King of Siluria. Coel had a SON who in turn had an unnamed GRANDSON who had a daughter named Alofe (Aife).

Alofe married Fiachadh III Streabhruine, 120th Ard Righ of Ireland, and their son was Muirreadhach Tireach , King of Connought, 122nd Ard Righ of Ireland.

Muirreadhach married Murien and their son was Eochaidh Moihmeodhain (Echu Mugmedón), 124th Ard Righ of Ireland.

Eochaidh married Carthan Casduff and their son was Niall Nóigiallach - Niall of the Nine Hostages, my ancestor and the ancestor of about 100 million other people.

Thus, Marcus Antonius is also my ancestor.

The figure below show that the various subpopulations within Europe are genetically distinct (Novembre et al. 2008). See my recent posting, Genes and Geography with a link to Razib's explanation of the structure of populations at Gene Expression [Genetic map of Europe; genes vary as a function of distance].

This data represents only a small percentage of the genetic variation in Europeans. Much of the remaining variation does not show a geographic distribution like the one in the figure because the variants arose much earlier. They have had time to spread to all subpopulations, or perhaps they pre-date the founding of the European population.

Novembre et al. also had to restrict their analysis to those 1,387 individuals who had both sets of grandparents from the same region. Many of the remaining group of 1,805 individuals did not know where their grandparents were born but a substantial number had grandparents from two different regions. What this means is that there is substantial ongoing gene flow between the various subpopulations

What does this have to do with Mark Antony? Quite a bit, actually. Looking at the figure from the Nature paper one can't help but be struck by what it says about population structure and gene flow in the past. The pink individuals in the upper left-hand have clearly been partially isolated from the rest of the European population for quite some time—equivalent to about 40-60 generations.

We know that this group has received alleles from Italy via Mark Antony and Niall of the Nine Hostages and probably from a great many other Italians who were living in Roman Britain. This level of gene flow amounts to just a trickle and the foreign alleles might easily be diluted out by random genetic drift.

We can think of gene flow in the opposite direction by considering what might have happened if a favorable allele had arisen in the Irish population about 1500 years ago. While it might have spread rapidly in Ireland, chance are it would not have made much impression in the rest of the European subpopulations until very recently. All bets are off now that humans have become so mobile but it is worth keeping in mind that the populations of most other species probably look a lot like ours did only a few centuries ago.

New beneficial alleles will not make much headway in 2000 years because gene flow between subpopulations is very low. There's no reason to assume that it was any different in the ancient past—it may even have been worse. Think about that the next time you hear about some hypothetical allele that arose 50,000 years ago and became fixed in the entire species. That's not very likely.


1. See comments. It looks like Genvissa, the presumed daughter of Claudius, is a mythical character made up many centuries after her presumed marriage to the King of the Siluria.

Novembre J, Johnson T, Bryc K, Kutalik Z, Boyko AR, Auton A, Indap A, King KS, Bergmann S, Nelson MR, Stephens M, Bustamante CD (2008) Genes mirror geography within Europe. Nature, Published online 31 August 2008 [doi:10.1038/nature07331]

Thursday, October 23, 2008

Niall Nóigiallach - Niall of the Nine Hostages

 
Niall Nóigiallach is a very famous man (Nóigiallach is Gaelic for "having Nine Hostages"). He was an Irish King who lived from about 350 to 405 AD. The "nine hostages" refers to hostages that he kept from each of the places that owed him allegiance.

Niall was fond of raiding the coast of Roman Britain and on one of those raids he captured a man named Maewyn Succat, who became a slave in Ireland. Succat eventually escaped, returned to Britain, and became a Christian missionary. He then went back to Ireland to convert the Irish heathens to Christianity. We know Maewyn Succat by his Christian name, Patrick, or Saint Patrick.

The reason Niall Nóigiallach is famous is because he is associated with the List of High Kings of Ireland, one of the oldest well-established genealogies in all of Europe. Anybody who connects to the lineage can trace ancestors back to about 100 AD.

Niall is also famous for another reason. DNA studies indicate that one in twelve Irish men carry a Y chromosome haplotype that traces back to Niall. The haplotype is also common in Scotland and England, and on the continent. This makes Niall one of only a handful of men who have millions of direct male descendants. (Genghis Khan was another [Genghis Khan a Prolific Lover, DNA Data Implies].)

Families that trace their ancestry back to Niall of the Nine Hostages include: (O')Neill, (O')Gallagher, (O')Boyle, (O')Doherty, O'Donnell, Connor, Cannon, Bradley, O'Reilly, Flynn, (Mc)Kee, Campbell, Devlin, Donnelly, Egan, Gormley, Hynes, McCaul, McGovern, McLoughlin, McManus, McMenamin, Molloy, O'Kane, O'Rourke and Quinn.

My mother's maiden name is Doherty. We are descendants of the O'Dochartaigh's of Donegal in the north-west part Ireland. Donegal is in the Republic of Ireland not in the part of Ulster that became what is now called "Northern Ireland", which is part of the United Kingdom. Donegal is near where the most intense spot on the DNA map is located.

My mother was hoping to establish the direct connection between her ancestors and the ancient lineage leading to Niall but it hasn't been possible. That was a big disappointment because I thought it would be fun to have a known ancestor from 400 AD.

Recently I discovered that my ancestors connect to the Niall lineage through English and through Scottish lines that are completely unrelated to the Doherty's. This shows, once again, that most people in England, Scotland, and Ireland are related if you go back far enough. The fact that so many lineages connect to the Niall lineage is not as significant as you might think. It's mostly because that ancient lineage is so well known.

In my case, the connections come through Isabel de Clare, grandmother of Robert the Bruce of Scotland, and through Isabel Mar, the wife of Robert the Bruce. Niall Nóigiallach is one of my ancestors.

If your ancestors are from the British Isles, chances are pretty high that we are related if we go back 60 generations. We all have about a trillion potential ancestors back then but that's five orders of magnitude more than all the people who lived in the British Isles at that time.


Happy Mole Day!

 
Today is "Mole Day," celebrated as part of National Chemistry Week. You can read all about it on Adventures in Ethics and Science [Happy Mole Day! (What's a mole?)].

What do you mean, "it's not that kind of mole?"1


1. What would you call 6.02 × 1023 Cindy Crawford moles?

Bar Graphs, Pie Charts, and Darwin

One of Ms. Sandwalk's ancestors is William Playfair (1789 - 1823). Her great grandfather—the great-great-grandfather of my children—was John Playfair Leslie. John's mother is a direct descendant of William Playfair.

William Playfair was an interesting man for many reasons. He is most famous for inventing statistical graphs; especially pie charts and bar graphs. These were printed in his famous book, Commercial and Political Atlas, published in 1786. Two examples of figures from that book are shown here.

But that's not all that Playfair did. His biographers call him an "engineer, political economist and scoundrel." I won't talk about the "scoundrel" part except to mention that it's probably an accurate description. One of the more legal things he did was to participate in the storming of the Bastille on July 14, 1789. (See William Playfair for some of the less legal activities.)

William Playfair was born in Scotland and lived with his older brother John Playfair in Edinburgh. John Playfair was a distinguished Professor of Mathematics at the University of Edinburgh. Their other brother was the architect James Playfair.

William Playfair was trained as an engineer with Andrew Meikle, the inventor of the threshing machine. Following his apprenticeship, he joined the company Boulton & Watt in Birmingham, England. This company operated a large plant that manufactured steam engines. William Playfair was assistant to James Watt.

It was during his time in Birmingham that Playfair made the connection that's so important to readers of Sandwalk.


In Birmingham, William Playfair associated with the members of the Lunar Society and attended their meetings. In addition to Matthew Boulton and James Watt, his bosses, there were other members whose names may be familiar; Josiah Wedgewood, Joseph Priestly, and Erasmus Darwin. Erasmus is Charles Darwin's grandfather. Josiah Wedgewood was Charles Darwin's other grandfather.

I keep hoping that one or more of my ancestors would have known Charles Darwin or even been related. No such luck. This is as close as it gets. My wife and children have an ancestor who hung out with Erasmus Darwin and Josiah Wedgewood.

I'm jealous.


Society Without God

 
From Amazon.com.
Before he began his recent travels, it seemed to Phil Zuckerman as if humans all over the globe were “getting religion” — praising deities, performing holy rites, and soberly defending the world from sin. But most residents of Denmark and Sweden, he found, don’t worship any god at all, don’t pray, and don’t give much credence to religious dogma of any kind. Instead of being bastions of sin and corruption, however, as the Christian Right has suggested a godless society would be, these countries are filled with residents who score at the very top of the “happiness index” and enjoy their healthy societies, which boast some of the lowest rates of violent crime in the world (along with some of the lowest levels of corruption), excellent educational systems, strong economies, well-supported arts, free health care, egalitarian social policies, outstanding bike paths, and great beer.

Zuckerman formally interviewed nearly 150 Danes and Swedes of all ages and educational backgrounds over the course of fourteen months, beginning in 2005. He was particularly interested in the worldviews of people who live their lives without religious orientation. How do they think about and cope with death? Are they worried about an afterlife? What he found is that nearly all of his interviewees live their lives without much fear of the Grim Reaper or worries about the hereafter. This led him to wonder how and why it is that certain societies are nonreligious in a world that seems to be marked by increasing religiosity. Drawing on prominent sociological theories and his own extensive research, Zuckerman ventures some interesting answers.

This fascinating approach directly counters the claims of outspoken, conservative American Christians who argue that a society without God would be hell on earth. It is crucial, Zuckerman believes, for Americans to know that “society without God is not only possible, but it can be quite civil and pleasant.”

”Most Americans are convinced that faith in God is the foundation of civil society. Society Without God reveals this to be nothing more than a well-subscribed, and strangely American, delusion. Even atheists living in the United States will be astonished to discover how unencumbered by religion most Danes and Swedes currently are. This glimpse of an alternate, secular reality is at once humbling and profoundly inspiring — and it comes not a moment too soon. Zuckerman’s research is truly indispensable.”
—Sam Harris
It's not just Denmark and Sweden. Many European countries are essentially secular as are many parts of Australia, New Zealand and Canada. Even in the USA, there are pockets of the country where the influence of religion is minimal.

Wake up Christians. Your religion is becoming increasingly superfluous. There's no point in being religious.


[Hat Tip: RichardDawkins.net]

Is Religion Here to Stay?

 
In the comments of a recent posting we heard the oft-repeated argument that a majority of Americans are believers and nothing is going to change that. It's an example of an irrational argument but it seems to be part of the defense mechanism of most believers.

I don't think it's true. I think the USA will change, just as Western Europe has changed. Here's what PZ Myers calls [A heartening graph].

There is one other possibility that some of my colleagues fear. Instead of a slow steady evolution away from superstition, we may see an ugly revolution in the USA as the two sides of the debate adopt mutually antagonistic points of view. There's an argument to be made that what many of us see as a hopeful sign is actually the precursor to establishment of a religous fundamentalist state—or at least a civil war where the attempt is made.




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.


Wednesday, October 22, 2008

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.


Tuesday, October 21, 2008

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?


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.


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]

Monday, October 20, 2008

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 Plac 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 provided there's no glucose around. Glucose is always the preferred carbon source.

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."


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.