Stop the Press!!! Scientists Discover the 7th and 8th Bases of DNA!

Science Daily published a press release from the University of North Carolina School of Medicine: Researchers Identify Seventh and Eighth Bases of DNA. The news was so extraordinary that the article was copied on RichardDawkins.net. Here's the opening paragraphs from the press release ...

ScienceDaily (July 21, 2011) — For decades, scientists have known that DNA consists of four basic units -- adenine, guanine, thymine and cytosine. Those four bases have been taught in science textbooks and have formed the basis of the growing knowledge regarding how genes code for life. Yet in recent history, scientists have expanded that list from four to six.

Now, with a finding published online in the July 21, 2011, issue of the journal Science, researchers from the UNC School of Medicine have discovered the seventh and eighth bases of DNA.

These last two bases -- called 5-formylcytosine and 5 carboxylcytosine -- are actually versions of cytosine that have been modified by Tet proteins, molecular entities thought to play a role in DNA demethylation and stem cell reprogramming.

...

Much is known about the "fifth base," 5-methylcytosine, which arises when a chemical tag or methyl group is tacked onto a cytosine. This methylation is associated with gene silencing, as it causes the DNA's double helix to fold even tighter upon itself.

Last year, Zhang's group reported that Tet proteins can convert 5 methylC (the fifth base) to 5 hydroxymethylC (the sixth base) in the first of a four step reaction leading back to bare-boned cytosine.

Speaking of textbooks, this amazing discovery couldn't have come at a better time since I'm just wrapping up the final chapters of my introductory biochemistry book. I'd better review what I wrote to see if I can include the 7th and 8th bases. Here's what I've got so far ...

DNA and RNA contain a number of modified nucleotides. The ones present in transfer RNA are well known (Section 21.8B) but the modified nucleotides in DNA are just as important. Some of the more common modified bases in DNA are shown in Figure 18.17. Most of them are only found in a few species or in bacteriophage while others are more widespread.

We will encounter N6-methyladenine in the next chapter when we discuss restriction endonucleases. 5-Methylcytosine is a common modified base in mammalian DNA because it plays a role in chromatin assembly and the regulation of transcription. About 3% of all deoxycytidylate residues in mammalian DNA are modified to 5-methylcytidine.

Oh dear. Looks like I've made a serious mistake. I've shown bases #5, #6, #7, #8, #9, and #10 but everyone knows that up until yesterday only six bases were known.

Where did I go wrong? Can anyone help me out before I have to send this chapter to the printer?¹

(The original Science paper is Ito et al. (2011). The authors really do imply that there are only six known modified nucleotides but they add an important qualifier that seems to have been played down the press release.)

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1. One of my sources is Gomers-Apt and Borst (1995). In addition to the modified bases I've shown above they describe three forms of glycosylated hydroxymethyl cytosine (#11, #12, #13), uracil (#14), α-putrescinylthymine (#15), two different sugar substituted forms of 5-dihydroxypentyluracil (#16, #17), a-glutamylthymine (#18), 7-methylguanine (#19), N⁶-carbamoylmethyladenine (#20), N⁶-methylcytosine (#21), three versions of glycosylated 5-hydroxycytosine (#22, #23, #24) and β-D-hydroxymethyluracil (#25).

Gommers-Ampt, J.H. and Borst, A.P. (1995) Hypermodified bases in DNA. FASEB 9: 1034-1042 [FASEB]

Ito, S., Shen, L., Dai, Q., Wu, S.C., Collins, L.B., Swenberg, J.A., He, C., and Zhang, Y. (2011) Tet Proteins Can Convert 5-Methylcytosine to 5-Formylcytosine and 5-Carboxylcytosine. Science Published Online 21 July 2011 [doi:10.1126/science.1210597]

Happy Birthday from Google!

Google wishes happy birthday to ..... ?

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Horace Judson (1931 - 2011)

Horace Freeland Judson died on May 6, 2011. He is best known as the author of The Eighth Day of Creation first published in 1979 and later re-published in an expanded edition in 1996. This is a "must-read" book for all students of biochemistry and molecular biology.

Mark Ptashne has published an obituary in PLoS Biology [Horace Judson (1931 - 2011)]. Ptashne raises an issue that should be of concern to all biological scientists; namely, the fact that modern molecular biologists seem to be completely unaware of the history of their field and of all the fundamental work done with bacteria and bacteriophage. This was a problem that Judson tried hard to rectify before it was too late but it's beginning to look like he was not successful.

Here's Ptashne's take on it.

The Eighth Day, first published in 1979, is a gift that keeps on giving. It is not the completeness of his history, nor even the vivid prose that imparts its lasting effect. Rather, Judson had the drive and wit to probe until he understood not just who did what, and with what quirks of personality, but why they did it, and how they did it. At each stage he reveals what was at stake, what the crucial alternatives were, and how the problems were solved (or not, as the case may be). Who cares about this past, you might ask, we scientists being neither artists nor composers?

Could it be that—for scientists as well as composers and artists—the past can be a source of inspiration, and that we ignore it at our peril? Consider the question of how states of gene expression are conveyed from mother to daughters as cells divide. Are instructions passed along by regulatory proteins present in the cytoplasm (so-called “cytoplasmic determinants”), or is the information somehow built into, or attached to, the DNA and transferred along with it? Experiments performed by Francois Jacob and Jacques Monod and their colleagues at the Institut Pasteur in the 1960s distinguish between the models, strikingly supporting the first of these possibilities. These experiments (including the famous “zygotic induction” and “PaJaMa” experiments—see Judson's book) were, of course, performed with bacteria.

I recently spoke with an editor of a major journal that regularly publishes sensational papers on the question as it applies to higher organisms, and learned that s/he, like many of the journal's authors, had never heard of these bacterial experiments! You realize, reading Judson's book, that the challenge is to engage the thought processes of these French scientists, ponder their approaches and results, and design experiments of comparable power and clarity to confirm or refute their conclusions in a different setting. Without that engagement, the new answers are apt to be (and in my opinion usually are) baloney.

Shortly after I read this obituary I was browsing Biology News Net and came across this remarkable opening statement in a press release from Stowers Institute for Medical Research in Kansas City, Missouri, USA.

Look up “transcription”—the copying of a gene’s DNA into RNA intermediaries—in any old molecular biology text book, and it all seems very simple: RNA polymerase II, the enzyme that catalyzes the reaction, assembles at the start site and starts motoring down the strand, cranking out the RNA ribbon used to construct proteins. But researchers now know that RNA polymerase II often stalls on DNA strands where it was once assumed to just barrel down.

A report from the Conaway lab at the Stowers Institute for Medical Research in the July 8, 2011, edition of the journal Cell identifies a switch that allows RNA polymerase to shift gears from neutral into drive and start transcribing. This work sheds light on a process fundamental to all plant or animal cells and suggests how transcriptional anomalies could give rise to tumors.

This is a very misleading statement. Back in 1989 I wrote an extensive section on "RNA Polymerase Pauses While Transcribing Some Sequences" in my first textbook. I described the effects of sequence and secondary structure on the rate of elongation and explained how a protein component of the the transcription complex (NusA) promotes pausing in order to enhance transcription termination. The idea that rates of elongation were NOT constant was an important part of most molecular biology textbooks.

But this was in bacteria (E. coli), where most of these fundamental discoveries were first made. The press release refers specifically to eukaryotic RNA polymerase II. In the second edition of my textbook (1994) I talked about RNA polymerase II elongation factors (eukaryotes) and specifically mentioned that "TFIIS may play a role in pausing and transcription termination that is similar to the role of NusA in bacteria." The point is that older molecular biology textbooks were well aware of the fact that even the eukaryotic transcription elongation complexes did not move at a constant rate. The press release is quite incorrect.

The actual paper is not about transcription elongation but transcription initiation and how various factors assist in the transfer from the initiation complex to the elongation complex. All this was known for transcription in E. coli back in the 1970s. The old molecular biology textbooks explain abortive initiation and how RNA polymerase can stall at initiation sites until sigma factors are replaced by elongation factors. None of that is new in spite of what the press release implies.

How does this happen? I think it's because modern researchers are completely unaware of the history of their field. That's partly because the work on bacteria and bacteriophage—where the basic concepts were often discovered—is no longer taught in biochemistry and molecular biology courses. This leads to the false idea, as expressed in the press release, that all new discoveries in eukaryotes are truly new concepts that nobody ever thought of before.

The solution to this problem is to make all students read The Eighth Day of Creation.

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Insulting Religion by Pat Condell

The accommodationists aren't gonna like this ...

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Evolution According to the Canadian Society for Ecology and Evolution

The National (USA) Center for Science Education (NCSE) has just endorsed a four-year-old statement on teaching evolution from the Canadian Society for Ecology and Evolution [Canadian Society for Ecology and Evolution adds its voice for evolution]. Here's the text from the CSEE website [CSEE/SCEE President's Forum].

There is overwhelming evidence that life has evolved over thousands of millions of years. The ancestors of modern organisms, as well as whole groups that are now completely extinct, have been found in great abundance as fossils. The main processes responsible for evolutionary change, such as variation and natural selection, have been repeatedly observed and verified in natural populations and in laboratory experiments. All the features of living organisms, including those discovered in the recent advances in molecular biology, are readily explained by the principles of evolution. Any scientific theory that provides a clear mechanism, offers a broad explanation of natural phenomena, receives strong support from observation and experiment and that is never refuted by careful investigation is usually called a “fact”. The cell theory of organisms, the germ theory of infection, the gene theory of inheritance and the theory of evolution are all facts. Teaching alternative theories as though they had equivalent scientific status is a perversion of education that damages children’s ability to understand the natural world. In particular, creationism is a religious doctrine long since known to be a fallacious account of Earth history that has no scientific standing and cannot be represented as a credible alternative to evolution. Evolution is the single most important principle of modern biology and the foundation of any sound biology curriculum.

Graham Bell
President, Canadian Society for Ecology and Evolution

I don't like this statement because: (1) it implies that the "theory of evolution" is only about variation and natural selection, (2) it confuses evolutionary theory with the facts of evolution, and (3) it confuses creationism with Young Earth Creationism.

If you are going to claim that your version of evolutionary theory is correct then you would be well-advised to define it. And if you are going to claim that it's a fact then what's the point of calling it "evolutionary theory"? The "theory" part of evolution is an explanatory model that's used to understand and interpret various facts about the history of life.

With respect to point #3, one of the main threats to science these days comes from Intelligent Design Creationism and there are many IDiots who do not subscribe to an obviously "fallacious account of Earth's history."

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Can Somebody Please Translate This?

Denise O'Leary has discovered a paper that was written up in Science News Daily: Chromosomes' Big Picture: Similarities Found in Genomes Across Multiple Species; Platypus Still out of Place. She seems to think this causes a problem for evolution.

I couldn't make head nor tail of the posting on Uncommon Descent [Most life forms show S pattern in chromosome lengths, guess which one doesn’t?] but that didn't surprise me because, after all, it was written by an IDiot. However, I was a bit surprised by the Science News report because I couldn't understand it either.

So I looked at the original paper. Here's the reference and abstract.

Li, X., Zhu, C., Lin, Z., Wu, Y., Zhang, D., Bai, G., Song, W., Ma, J., Muehlbauer, G.J., Scanlon, M.J., Zhang, M., and Yu, J. (2011) Chromosome Size in Diploid Eukaryotic Species Centers on the Average Length with a Conserved Boundary. Mol. Biol. Evol. 28: 1901-1911. [doi: 10.1093/molbev/msr011]

Abstract

Understanding genome and chromosome evolution is important for understanding genetic inheritance and evolution. Universal events comprising DNA replication, transcription, repair, mobile genetic element transposition, chromosome rearrangements, mitosis, and meiosis underlie inheritance and variation of living organisms. Although the genome of a species as a whole is important, chromosomes are the basic units subjected to genetic events that coin evolution to a large extent. Now many complete genome sequences are available, we can address evolution and variation of individual chromosomes across species. For example, “How are the repeat and nonrepeat proportions of genetic codes distributed among different chromosomes in a multichromosome species?” “Is there a general rule behind the intuitive observation that chromosome lengths tend to be similar in a species, and if so, can we generalize any findings in chromosome content and size across different taxonomic groups?” Here, we show that chromosomes within a species do not show dramatic fluctuation in their content of mobile genetic elements as the proliferation of these elements increases from unicellular eukaryotes to vertebrates. Furthermore, we demonstrate that, notwithstanding the remarkable plasticity, there is an upper limit to chromosome-size variation in diploid eukaryotes with linear chromosomes. Strikingly, variation in chromosome size for 886 chromosomes in 68 eukaryotic genomes (including 22 human autosomes) can be viably captured by a single model, which predicts that the vast majority of the chromosomes in a species are expected to have a base pair length between 0.4035 and 1.8626 times the average chromosome length. This conserved boundary of chromosome-size variation, which prevails across a wide taxonomic range with few exceptions, indicates that cellular, molecular, and evolutionary mechanisms, possibly together, confine the chromosome lengths around a species-specific average chromosome length.

Here's the challenge. Read the abstract and try and guess what important scientific point the authors are making that deserves publication in a molecular evolution journal. For extra points, read the entire article and see if you can improve your guess. You'll be impressed when you read the discussion and it all becomes clear (not!)

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Polaris 25 - The Skeptical Track

Polaris 25 will take place this coming Friday, Saturday, and Sunday (July 15-17) at the Sheraton Parkway Toronto North in Richmond Hill, just north of Toronto. It will celebrate the 45th anniversary of Star Trek. Three of the actors from Stargate SG-1/Stargate Atlantis will be there—that's my favorite TV series (now in re-runs).

The Centre For Inquiry and its Committee for the Advancement of Scientific Skepticism (CASS) has been invited to present a Skeptical Track at the convention. The four speakers are ....

• Me (Larry Moran): "What’s the Difference Between Science and Science Fiction?"


• Jeffrey Shallit: "Misinformation Theory: How Creationists Abuse Mathematics."


• Chris Hassall: "The Evolution of Superstition: People, PCs and Pigeons."


• Alex Manafu: "Could Science Prove the Existence of God? (Or, Must Science Be Naturalistic?)"

For more information see Jeffrey Shallit's blog Recursivity: See me at Polaris 2011 in Toronto - July 16 and Michael Kruse's blog at Skeptic North: Skeptical Track at Polaris 25.

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Carnival of Evolution #37

This month's Carnival of Evolution (37th version) is hosted by William, a 13 year old budding evolutionist who lives in Petawawa, Ontario, Canada [Carnival of Evolution #37-Happy Canada Day!]. His blog is The Lessons of Evolution.

The next edition will be hosted right here on Sandwalk! (Canadians are taking over the world.) Email me if you have posted something on evolution that deserves to be in the next carnival. Or just send me a link if you come across something posted by someone else. (l(dot)moran(at)utoronto(dot)ca)

I even accept postings from adaptationists and (maybe) evolutionary psychologists. I also promise to give serious consideration to postings from (some) philosophers.

There will be a new surprise category in next month's carnival—watch for it!

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The Scientific American Blog Network

Today marks the launch of another blog network. This one is The Scientific American Blog Newtork. Bora Zivkovic is the man behind it.

I read about thirty blogs on a regular basis. Some of them have migrated two or three times over the past five years and I always follow them because they are good blogs. I really don't care whether the blogs I follow are part of a network or not. I don't read the other blogs in a network because my aggregator gives me a direct feed.

What's the purpose behind belonging to a blog network? Does it provide something that you can't get by being an independent blogger? Is it money? Are there any downsides other than the fact that you are lending your name to support for a profit making corporation? If you're supporting a magazine like Discover, Seed (now dead), Nature, or Scientific American does it mean that you stand behind whatever they print?

The thing I find most annoying about commercial blogs is the advertising—some of which is contrary to what's being posted. Is the "profit" to the blogger really significant enough? Maybe it is for PZ Myers but the income for someone like me was peanuts when I last explored that option.

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Does This Belong in a Scientific Journal?

The other day I was browsing through recently published papers in PLoS Biology and came across this one.

Field D, Amaral-Zettler L, Cochrane G, Cole JR, Dawyndt P, et al. 2011 The Genomic Standards Consortium. PLoS Biol 9(6): e1001088. doi:10.1371/journal.pbio.1001088.

Abstract

A vast and rich body of information has grown up as a result of the world's enthusiasm for 'omics technologies. Finding ways to describe and make available this information that maximise its usefulness has become a major effort across the 'omics world. At the heart of this effort is the Genomic Standards Consortium (GSC), an open-membership organization that drives community-based standardization activities, Here we provide a short history of the GSC, provide an overview of its range of current activities, and make a call for the scientific community to join forces to improve the quality and quantity of contextual information about our public collections of genomes, metagenomes, and marker gene sequences.

I'm interested in this sort of thing since back in the olden days (1993) I spent a bit of time at GenBank exploring annotation issues with a view to correcting the growing number of errors that were being propagated in online databases.

It's an insoluble problem and I doubt very much that a new organization is going to help.

But that's not what I want to talk about. Near the end of the article in PLoS Biology you find this paragraph.

The Internet has resulted in a Cambrian explosion of productivity and data sharing through the adoption of a huge stack of agreed-upon protocols (standards) that allow many devices and programs to communicate to the transformative benefit of the everyday user [26]. Enabling access to user-generated content is key to harnessing the resources of a distributed community: Flickr has over 5 billion photographs uploaded, and Wikipedia has over 3.5 million English articles as of this writing. Standards for organizing sequence data will be similarly needed as sequencing instruments themselves, especially as these instruments are more and more commoditized and owned by individuals rather than institutions.

I'm sad to find this sort of content-free language creeping into scientific journals. We've been spared up to now but it looks like the 23 scientists listed as authors feel comfortable with this new style of writing.

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Losing Charlemagne

Back in October 2009 I published my genealogical connection to Emperor Charlemagne [My Family and Other Emperors]. It is wrong. I relied too much on the information found in Ancestry.com and much of that information is unreliable.

In my case the connection was through Ruhamah Hill (b ~1708) who married John Belden (1728 - ). They were British citizens who lived in Norwalk, Fairfield Country, Connecticut (a colony of Great Britain). The parents of Ruhamah Hill are often listed as William Hill and Abigail Barlow of Greenfield Connecticut but there's no evidence to support this connection. On the other hand, historical records say that Ruhamah Hill is the daughter of Captain John Hill (1669 - 1768?) of Westerley, Rhode Island and this seems much more reasonable since Captain John Hill married Ruhamah Wyer (1670 - ).

There goes my connection to Charlemagne and all of the other notables on the list.

Not to worry. The probability is high that I am a descendant of Charlemagne just like most others with any European blood [Are You a Descendant of Charlemagne?]. There are two other connections in my genealogy. I'm working on conformation.

Ms Sandwalk doesn't seem to have any ancestors that connect to European royalty but she is related to a number of very interesting people. Unfortunately, she's too embarrassed to let me mention them in public.

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For Your Amusement

vjtorley (Vincent Joseph Torley) has posted on Uncommon Descent. The title of his posting is Someone’s wrong. Who is it?. The issues is whether the similarities of mammalian embryos is PREDICTED by modern evolutionary theory. PZ Myers says "no" and Ken Miller probably agrees. They are both correct.

Do those similarities provide support for common descent even though they may not have been predicted by evolutionary theory? Yes, they do, in the same sense that common pseudogenes support evolution even though pseudogenes are not a necessary part of modern evolutionary theory.

So here's the question ... who is wrong about this issue?

1. PZ Myers
2. Ken Miller
3. Vincent Joseph Torley

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New York Legalizes Same-Sex Marriage

Same-sex marriage is legal in ten countries (Argentina, Belgium, Canada, Iceland, the Netherlands, Norway, Portugal, South Africa, Spain and Sweden). In Canada it has been legal for gays and lesbians to marry since July 20, 2005.

In the United States same-sex is legal in Connecticut, Iowa, Massachusetts, New Hampshire, Vermont, and the District of Columbia). A few hours ago it became legal in New York. I wonder if this will cause other states to make same-sex marriage legal?

The map shows where gays and lesbians have the same rights as other citizens and where those rights are restricted. I think it reflects a deep cultural divide in America and I wonder where this is going to end up? Is it possible that some of the red colored states will eventually change their minds on this issue?

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[Image Credit: modified from Wikipedia]

The Religious Left in Canada

The New Democratic Party's "Faith and Social Justice Commission" has produced a video to prove that you can be religious and socialist.

My position is that religion should be kept out of politics. There should not be a "Faith and Social Justice Commission" sanctioned by the NDP. (Is there also an "Unfaith and Social Justice Commission" for all those atheists who believe in social justice?)

I have no problem with individuals adhering to one religion or another but keep it personal. There's no need to band together in order to influence policy within the government or even within a party. Frankly I don't care why you support socialist progressive policies as long as you do. Don't try and make it look like religion is what motivates you to favor the left because that just makes you look as silly as the right-wing fundamentalists who use religion to defend their position.

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[Hat Tip: Canadian Atheist]

For Your Amusement

Bill Dembski has just posted an article titled Who Will Be Michele Bachmann’s Science Advisers?.

This is deeply ironic on many levels. Why would Bachmann need people to advise her about science? So far she's gotten along just fine without knowing a thing about science. A real science adviser would just confuse her.

I wonder if Dembski has anyone in mind? He surely can't be thinking of himself or any of his closest IDiot friends because, as we all know, there are Nobel Laureates who would be far better qualified.

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