Modified Bases in DNA

 
Adenine: from the Greek adenas "gland": first isolated from pancreatic glands (1885)

Cytosine: derived from cyto- from the Greek word for "receptacle," refering to cells (1894)

Guanine: originally isolated from "guano" or bird excrement (1850)

Thymine: first isolated from thymus glands (1894)

(source Horton et al. 2006)Bacterial genomes contain a number of unusual bases in addition to the classic adenine (A), cytosine (C), guanine (G), and thymine (T). The most common of the unusual bases are 5-methylcytosine, N⁴-methylcytosine, and N⁶-methyladenine (Erlich et al. 1987).

Bacteriophage DNA, especially the DNA of bacteriophage T4 and its close relatives, can contain 5-hydroxymethylcytosine. The base is usually glycoslylated in normal phage. (A sugar group is attached to the hydroxymethyl group.)

Many of these modified bases serve to protect DNA from restriction endonucleases—enzymes that cleave foreign DNA at specific sites. The restriction endonucleases act on bacteriophage (virus) DNA preventing it from replicating inside the bacterial cell [see Restriction, Modification, and Epigenetics].

If bacteriophage modify their nucleotides at the site of cleavage, they will escape the defenses of the bacterial cell. Of course, bacteria that make restriction endonucleases have to protect their own DNA or else they will be committing suicide. That's why their genomes have modified nucleotides.

Many other modified bases have been found in DNA but they are quite rare. Examples are uracil, α-putrescinylthymine, and 5-dihydroxypentyluracil.


Eukaryotic DNA doesn't have as many modified bases. In fact, 5-methylcytosine is the only one that's common in all eukaryotes. N⁶-methyladenine is known to exist in protist and plant DNA and it is thought to exist at low levels in mammalian DNA as well (Ratel et al. 2006). The presence of hydroxymethycytosine has been reported in various animals as far back as 1972 (Penn et al. 1972).


Now Kriaucionis and Heintz (2009) have re-discovered hydroxymethylcytosine in mammalian DNA. Their paper appears in the latest issue of Science. Apparently the modified nucleotide is found in certain brain cells. Their result confirms the work done by Penn et al. (1972), a result that had not been confirmed in several other studies. This makes hydroxymethylcytosine the seventh modified base in eukaryotic DNA—unless there are some that I don't know about.

The problem with the press release is that it doesn't put the discovery in the proper context.

ScienceDaily (Apr. 17, 2009) — Anyone who studied a little genetics in high school has heard of adenine, thymine, guanine and cytosine – the A, T, G and C that make up the DNA code. But those are not the whole story. The rise of epigenetics in the past decade has drawn attention to a fifth nucleotide, 5-methylcytosine (5-mC), that sometimes replaces cytosine in the famous DNA double helix to regulate which genes are expressed. And now there's a sixth: 5-hydroxymethylcytosine.

In experiments to be published online April 16 by Science, researchers reveal an additional character in the mammalian DNA code, opening an entirely new front in epigenetic research.

We aren't told that the sixth nucleotide is actually N⁶-methhyladenine. We aren't told that many other modified bases have been discovered in bacteria, including hydroxylmethylcytosine. And we aren't told that the authors actually cite earlier work showing the presence of hydroxymethylcytosine in mammalian DNA.

That's a shame. The authors are quoted in the press release. They should have made more of an effort to ensure that it was scientifically accurate.

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Ehrlich, M., Wilson, G.G., Kuo, K.C., and Gehrke. C.W. (1987) N4-methylcytosine as a minor base in bacterial DNA. J Bacteriol. 169:939-943. [Journal of Bacteriology]

Kriaucionis, S. and Heintz, N. (2009) The Nuclear DNA Base 5-Hydroxymethylcytosine Is Present in Purkinje Neurons and the Brain. Science Published Online April 16, 2009 [DOI: 10.1126/science.1169786]

Penn, N.W., Suwalski, R., O'Riley, C., Bojanowski, K. and Yura, R. (1972) The presence of 5-hydroxymethylcytosine in animal deoxyribonucleic acid. Biochem J. :781–790. [Biochem. J.]

Ratel, D., Ravanat, J.L., Berger, F., and Wion, D. (2006) N6-methyladenine: the other methylated base of DNA. Bioessays :309-15. [PubMed

Dancing in Antwerp's Train Station

 
I have a confession to make. Ms. Sandwalk and I, along with four other couples we've known for many years, are learning how to do ballroom line dances. It's so much fun.

Perhaps that's why this video makes me smile. It's a promotion by a Belgian TV show that's looking for a "Maria" to play the lead in "The Sound of Music." I hope my daughter—who lives in Belgium— never hears about it 'cause she already knows all the words to every song in the musical.



UPDATE: Some people may not know about the T-Mobile add in the Liverpool Street Station in London [T-Mobile Dance].

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P.S. My dancing group is almost as good as these guys. Maybe we should do a performance in Union Station in downtown Toronto?

[Hat Tip: GrrlScientist]

Jerry Coyne's View of Evolutionary Psychology

 
You'll have to read Evolutionary psychology: the adaptive significance of semen flavor to find out what Coyne thinks of evolutionary psychology. I think he's captured the essence of the movement.

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P.S. I was looking for an appropriate illustration of the behavior that Coyne describes. Turns out that if you enter the appropriate term in your Google search box, you'll find quite a few photographs out there on the internet. I decided not to use any of them but the search was interesting.

Do You Want to Know the Sequence of Your Genome?

 
It's very likely that each one of us carries several recessive lethal alleles and many alleles that make us more susceptible to various diseases. You can count on it.

Do you want to know which of the many known deleterious alleles you have in your genome? That's one of the questions asked in an article published in The Economist: Getting Personal.

Though he has the world’s most advanced gene-sequencing technology at his fingertips, Dr Altshuler refuses to get his own genome sequenced: “If someone gave it to me on a CD, I’d refuse to look at the disc. The information is meaningless.” Bill Gates agrees. He has not had his genome sequenced either, nor does he plan to, though after a moment’s reflection he adds, “unless I find out I have cancer.”

Keep in mind that there's nothing much you can do if you find out that you have a predisposition for cancer or some other disease, like Alzheimer's. You can change your lifestyle but it's not clear whether that will change the probabilities significantly. Furthermore, there are so many claims out there about how to prevent disease that you'll never be sure you're doing the right thing.

And what do you do if you want to have children with someone who also knows their genome sequence? Figure out the probabilities that your children will not inherit any of your bad alleles. Is that a responsibility that you want? Why?

I'm with David Altshuler on this one and so was John Hawks until recently. Now John is changing his mind—Turning ACGT into poetry. Part of my problem is that I don't feel very comfortable seeking advice from a for-profit company when it comes to interpreting my genome sequence. But we won't have much choice; there's absolutely no way that the average person is going to be able to do the interpretation, so they will have to pay for it. And they'll have to get an update every few years as we learn more about human genes. (Whole genome interpretation is not a service that will be covered by socialized medicine.)

Do you want to know the sequence of your genome? Assuming that you can afford the sequencing cost, how do you intend to use the information and how will you interpret it?

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Sign the Open Letter

 
Are you a Canadian scientist who is upset about cuts to research funding by the current government? Read the Open letter to the Prime Minister and Leader of the opposition and add your name to the list of over 2000 scientists.

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Proportional Representation Is about to Pass in British Columbia

 
The Single-Transferable Vote (STV) is a system where each voting district (riding/constituency) has multiple members. You vote for several candidates by ranking them from most preferred to least preferred. If a candidate gets more than the minimum number of votes needed for election then the "surplus" votes are transferred to the second choice candidates.

If, after transferring "surplus" votes, there are still candidates to be elected, then the candidate with the lowest number of votes is eliminated and the votes are transferred to the voter's next choice. This process of elimination and transfer continues until the required number of candidates are elected [BC-STV].

The system was chosen by a non-partisan citizens' assembly.



A majority of voters in British Columbia voted in favor of this form of proportional representation in the last referendum but they failed to get the 60% majority required to change the voting system. It looks like they will succeed on May 12th, making British Columbia the first province to abolish the old first-past-the-post system and adopt a form of proportional representation.

I'm certain that Ontario won't be far behind. We lost the vote for proportional representation last time but that was probably because the general public didn't understand it. That, plus the fact that many prominent newspaper columnists and editors lied made untrue statements about the dangers of proportional representation. They didn't understand it either.

April 15, 2009
FOR IMMEDIATE RELEASE
Poll: 65 per cent of British Columbians support BC-STV
Younger voters overwhelming in their support

Vancouver, B.C. – The numbers are in and British Columbia voters are giving a big thumbs up to electoral reform with 65 per cent saying they will vote for BC-STV in the upcoming referendum on May 12. That is the top line result of a major survey conducted by Angus Reid Strategies. Support for a new way of electing our MLAs is particularly strong among younger voters – those 18 to 34 – at 74 per cent.

“The survey results indicate that British Columbians and particularly younger voters are ready to embrace a new electoral system in British Columbia,” said Catherine Rogers, vice president, Angus Reid Strategies. “A large majority are looking for electoral change and want an electoral system that is fair and that elects MLAs who are more accountable to them.”

When presented with the question that will appear on the ballot, 65 per cent said yes to BC-STV while only 35 per cent chose to keep the current first-past-the post system. Angus Reid Strategies conducted the online survey March 9 to 12 and polled 702 British Columbians across the province. While support for BC-STV continues to grow, awareness of the upcoming referendum is at 44 per cent.

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The 50 Most Brilliant Atheists of All Time

 
The 50 Most Brilliant Atheists of All Time

Congratulations to Jodie Foster (#46) who's a lot more attractive than atheist #45 who, in turn, is a heck of a lot prettier than #37.

1. Democritus
2. Diagoras of Melos
3. Epicurus
4. Theodorus the Atheist
5. Andrew Carnegie
6. Ivan Pavlov
7. Sigmund Freud
8. Clarence Darrow
9. Richard Strauss
10. Bertrand Russell
11. Jawaharlal Nehru
12. Linus Pauling
13. Paul Dirac
14. Ayn Rand
15. Katherine Hepburn
16. Jacques Monod
17. Subrahmanyan Chandresekhar
18. Alan Turing
19. Francis Crick
20. Claude Shannon
21. Richard Feynman
22. Noam Chomsky
23. James D. Watson
24. Peter Higgs
25. Warren Buffet
26. John Searle
27. Steven Weinberg
28. Carl Sagan
29. David Suzuki
30. George Carlin
31. Bruce Lee
32. Leonard Susskind
33. Stephen Jay Gould
34. Richard Dawkins
35. Daniel Dennett
36. Stephen Hawking
37. Mick Jagger
38. Richard Leakey
39. David Gilmour
40. Brian Eno
41. David Sloan Wilson
42. Steve Wozniak
43. Douglas Adams
44. Steven Pinker
45. PZ Myers
46. Jodie Foster
47. Russell T Davies
48. David Chalmers
49. Sean Carroll
50. Mark Zuckerberg

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G T C A

 
Just when I've (almost) mastered Y M C A, along comes a new challenge.

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Summer Course on Intelligent Design Creationism

 
You can sign up for a full week course on Intelligent Design Creationism at the Discovery Institute in Seattle, Washington (USA) [Deadline Nears for Summer Seminars on Intelligent Design]. It runs from July 10 - 18, 2009 and it's free.

The course is open to any student ... almost. There are a few small hurdles that have to be jumped in order to qualify.

1. A copy of your resume;
2. A letter of recommendation from an ID-friendly source;
3. A copy of your academic transcript;
4. A short (one page) statement of your interest in ID within your field of study.

If anyone wants to attend I'd be happy to write a letter of recommendation.

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Christine Hurley - The Flamboyant Psychic

 
Back in October 2007, I posted a short message about a psychic who was arrested for fraud. I linked to Mike's Weekly Skeptic Rant because he had an interesting multiple choice question [see Psychic Arrested in Calgary].

A Calgary psychic named Christine Hurley posted a comment where she claimed to be as interested as the rest of us in weeding out psychic frauds. (Yes, I do see the irony.)

Since then, she has posted several more comments designed to promote her "skills" in psychic reading. You can benefit from her psychic powers by charging $120 to your credit card for a 30 minute phone reading [Christine Hurley: Prices]. An even better bargain is one hour on the phone for $150!

I'm not exactly sure how this works. Presumably Ms. Hurley will tell you all the important things you need to know in the first 30 minutes. Maybe there are some interesting details that require another half hour.

Read the comments and testimonials that are accumulating at Psychic Arrested in Calgary. It's really amazing to see how some people can be completely duped by Christine Hurley into believing that she has psychic powers.

I wonder why she spends so much time collecting $120 (CDN) from her suckers clients when she could "easily" pocket $1,000,000 (US) in James Randi's One Million Dollar Paranormal Challenge? Does anyone know why she hasn't collected the prize? As a true psychic she must know how Randi's test is going to turn out.

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[Photo Credit: Bryan Schlosser, The Leader-Post]

The Evolution Conspiracy

 
The Evolution Conspiracy is a book by Lisa Shiel. I'd never heard of her until a few days ago but some of you might know her because she's a fan of bigfoot. She has a masters degree in library science.

You can't buy the book until next September but you can read all the rave reviews of this unpublished book on Lisa's website: The Evolution Conspiracy. You can also get an inkling of what the book is about by reading her promotional material. Here's an excerpt ...

Evolution.

One word, deceptive in its simplicity, has transformed the way we look at ourselves and everything around us. Once thought of as unique, man has become one of the animals with no special claim on the planet. As children, few of us question what we learn in biology class about the origins of life and the position man holds in the hierarchy. Science textbooks present evolution as fact—indisputable, inevitable, and incomprehensible to everyone outside the exalted few with PhDs in the appropriate fields.

That’s why this book promotes one key premise—anyone can understand evolution.

That's refreshing. Anyone can understand evolution. Anyone, that is, except Lisa Shiel. Her stupidity and ignorance are on display in the comments she's making on science blogs and on her own website. By her own admission she is dropping comments on all the evolution blogs in order to promote her book [Banned by Evolutionists! Can You Handle It?].

The purpose of this posting is to help give her as much publicity as possible in order to expose her as just another kook who has no idea what evolution is all about.

Here's an example from a posting she made on April 7th: You Can’t Tell a Species by Its Cover.

The theory of evolution involves numerous complicated and confounding strands—almost as many strands, I dare say, as DNA itself. Charles Darwin posited that natural selection drives the evolution of species, and this idea has become the cornerstone of evolutionary theory. In natural selection, traits that seem beneficial are preserved in a species while undesirable traits gradually disappear. Because natural selection cannot account for all adaptations, scientists devised the theory of genetic drift, in which changes occur at random.

Yet no one has ever reproduced the creation of a species via either natural selection or genetic drift; in fact, no one has ever demonstrated scientifically that one species evolves into another. If a theory must adhere to the scientific method to remain a scientific theory, then evolution has failed the test. The scientific method requires repeated testing, and the ability to reproduce results.

Now toss into this mess the recent discovery that some species “evolve” genetically while remaining unchanged anatomically. Scientists at Massey University in New Zealand have found that a reptile called the tuatara differs genetically from its 8,000-year-old ancestors, while retaining the same anatomical makeup and outward appearance. The tuatara’s DNA changes make it the Speedy Gonzales of genetic evolution. According to Axel Meyer of Germany’s University of Konstanz, the discovery suggests “a real disconnect” can exist between genetic and anatomical evolution.

Finally, consider the recent discovery that cryptic species can fool us too—two creatures look identical, but their DNA identifies them as different species. Perhaps the fossilized tuatara aren’t really tuatara after all…

Evolution: The unscientific scientific theory.

Makes you wonder if Lisa Shiel has even read her own book—a book that presumably explains evolution correctly. There are so many factual and conceptual errors in this short posting that it catapults Lisa into contention for the most ignorant IDiot award. And that's saying a lot 'cause the competition is fierce.

Anyway, the bottom line is that there's nothing to see here folks. You can move along to other books and other blogs. Lisa even makes Denyse O'Leary look good.

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Nobel Laureate: Max Theiler

 

The Nobel Prize in Physiology or Medicine 1951

"for his discoveries concerning yellow fever and how to combat it"

Max Theiler (1899 - 1972) won the Noble Prize in 1951 for his work on combating yellow fever.

Theiler's most important contribution was the discovery of a variant of the yellow fever virus that did not cause the disease in humans. When injected into healthy patients, this variant produced immunity to the normal disease-producing virus.

This discovery was not immediately useful since attenuated virus from mice was more effective in producing immunity—a result also discovered by Theiler. The Nobel Committee felt that Theiler had made a significant contribution to understanding viral diseases.

One gets the impression from reading the presentation speech that Theiler was also being recognized as a representative of work done by the Rockefeller Foundation.

THEME:
Nobel Laureates

The significance of Max Theiler's discovery must be considered to be very great from the practical point of view, as effective protection against yellow fever is one condition for the development of the tropical regions - an important problem in an overpopulated world. Dr. Theiler's discovery does not imply anything fundamentally new, for the idea of inoculation against a disease by the use of a variant of the etiologic agent which, though harmless, produces immunity, is more than 150 years old. Jenner used a natural virus variant, cowpox virus, against smallpox, and Pasteur produced a similar variant of the rabies virus by repeated passage through animals. So far there have been only a few successful attempts to master a disease by such measures, but Dr. Theiler's discovery gives new hope that in this manner we shall succeed in mastering other virus diseases, many of which have a devastating, effect and against which we are still entirely powerless. Max Theiler, therefore, has rendered mankind such a service as Nobel made a condition for the awarding of this prize.

Dr. Theiler. For a period of almost forty years the International Health Division of the Rockefeller Foundation has carried on very comprehensive and fruitful work in combating yellow fever and extending our knowledge of it. Among the many who have made their contributions, you take an especially prominent place, because you have made their contributions profitable and because you have opened the way to greater understanding of the epidemiology of the disease and to an effective prophylaxis against it. The Caroline Institute esteems your research work so highly, not the least for its practical value, that it has found it proper to award this year's Nobel Prize in Physiology or Medicine to you.

I ask you, Dr. Theiler, to receive the prize from the hands of His Majesty, our gracious King.

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[Photo Credit: ©Bettmann/CORBIS, Rights Managed, Corbis]

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

Gary Goodyear's Letter to Nature

 
Canadian government reaffirms support for science and discovery

Sir

You report researchers' concerns about the Canadian government's support for science in two recent News stories (Nature 457, 646; 2009 and Nature 458, 393; 2009). As Minister of State for Science and Technology, I can say that, despite the global economic situation, the government of Canada remains committed to innovation and discovery. We have increased funding to researchers, both in universities and in the private sector.

In the past three years, for example, we have significantly increased the budgets of federal granting councils, increased scholarships through the Canada Graduate Scholarships Program, and increased the Industrial Research Assistance Program for small and medium-sized businesses. The Budget 2009 announcements include Can$750 million (US$590 million) for the Canada Foundation for Innovation to attract and retain world-leading researchers, and a Can$2-billion infrastructure programme. The government has also put in place two five-year funding agreements with Genome Canada that are worth Can$240 million, to support large-scale, world-class research.

Your readers should therefore rest assured that the government of Canada will continue to fund research for the benefit of all scientists and Canadians.

Isn't it strange that basic science researchers are upset about the fact that funding to the major granting councils has been cut for the next three years?

Either the researchers are correct, and Canadian basic research is in trouble, or Gary Goodyear is correct and the Conservatives are doing a fine job.

I know who is telling the truth.

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Do Science and Religion Conflict in Louisiana?

 
The National Center for Science Education reports on the results from a recent poll in Louisiana [Polling Evolution in Louisiana]. Respondents were asked the following question.

Do you think the scientific theory of evolution is well supported by evidence and widely accepted within the scientific community, or that it is not well supported by evidence and many scientists have serious doubts about it?

39% answered "yes" and 21% didn't know. 40% said that evolution is not well supported by evidence and/or is not accepted by the scientific community.

Let's dismiss the 21% who didn't know the answer. That leaves almost 80% of the population who see no conflict between science and religion. Half of them probably believe in a God who accepts evolution and the other half of them think that the scientists reject evolution, which maked science compatible with creationism.

That's pretty amazing, and scary, when you think about it.

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Teabagging

 
Today is April 15th. It's a significant day in America because income taxes are due. It's also the day when some people are protesting taxes by having "teabagging" parties. If you don't live in the USA, or watch American television, you've probably never heard of "teabagging." Here's a quick summary from a show that I watched on MSNBC.


Listen for Lawrence O'Donnell, who explains the importance of socialism in America. According to O'Donnell, America is like all other Western industrialized nations. It has a mixed economy (capitalism and socialism).

I agree with that. I don't agree with his claim that, compared to all other nations, American probably has the best mix of socialism and capitalism.

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