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Saturday, September 29, 2012

Douglas Axe Explains Molecular Evolution

There are several dozen scientists and graduate students in my department studying various aspects of protein evolution, structure, and folding. They've published dozens of papers but, apparently, they never realized that what they're studying is impossible. Douglas Axe, a leading Intelligent Design Creationist, sets them straight.

[Hat Tip: Evolution News & Views: Axe: Vive la Différence]

Where Am I?

My granddaughter, Zoë, took a picture of me getting a hot dog. Can you guess where I am?

Where Am I?

Wednesday, September 26, 2012

Ewan Birney: Genomics' Big Talker

My copy of Science arrived in the mail last week and I wasn't surprised to see the article by Elizabeth Pennisi on ENCODE Project Writes Eulogy for Junk DNA. Pennisi has long been skeptical about junk DNA. She advocates the position that what makes us human is hidden in the "dark matter" of the genome. She has never lost an opportunity to promote those scientists who claim to have discovered function in junk DNA so it was natural for her to fall hook-line-and-sinker for the recent ENCODE publicity campaign [see Science Writes Eulogy for Junk DNA].

What did surprise me was a three-page spread on Ewan Birney: Genomics' Big Talker, written by Elizabeth Pennisi. This is extraordinary. I don't know of another example where a leading science journal has promoted a young scientist in this manner. Of course, it's doubly extraordinary because, in this case, Science is promoting a scientist who just made some serious mistakes interpreting his own data! The man who is so prominently featured in the Sept. 7, 2012 issue of Science magazine is coming under serious criticism for letting publicity rule his science. He has almost single-handedly1 damaged the reputation of 400 scientists in the ENCODE Consortium and he did it, in part, because he was not knowledgeable about his own field of expertise! [see ENCODE Leader Says that 80% of Our Genome Is Functional and The ENCODE Data Dump and the Responsibility of Scientists]

UPDATE:A reader has reminded me that Science published two pages (online) on Felicia Wolfe-Simon at the time of the arsenic affair. Hmmmm ... is this the beginning of a pattern?

Tuesday, September 25, 2012

Viva Las Vegas!

Ms. Sandwalk and I are in Las Vegas with our friends. Posting may be a bit light for the next few days.

Monday, September 24, 2012

Where Am I #2?

Here's another clue. Where am I today? (Click to embiggen.)

Where Am I #1?

Can you guess where I am today? (Click to embiggen.)

Monday's Molecule #187

Last week's molecule was the core nucleosome complex [Monday's Molecule #186] and nobody who was eligible for a win got it! That's quite shocking. Here's an easy one for today.

Name this molecule, including the name of the "R" group. You'll have to guess but there's really only one possibility in living cells. Don't forget, I need the full name of the most likely molecule given the partial structure that you see.

Post your answer as a comment. I'll hold off releasing any comments for 24 hours. The first one with the correct answer wins. I will only post mostly correct answers to avoid embarrassment. The winner will be treated to a free lunch.

There could be two winners. If the first correct answer isn't from an undergraduate student then I'll select a second winner from those undergraduates who post the correct answer. You will need to identify yourself as an undergraduate in order to win. (Put "undergraduate" at the bottom of your comment.)

Sunday, September 23, 2012

On the Reasoning Ability of Most Creationists

Here's an excellent example of the difference between a scientific way of knowing and the other kind. Follow this link to the full story. I'm told that reddit user jerfoo wrote the story and took the photos.

I've often admired the jigsaw puzzle analogy to understanding the evidence for evolution. It's as though we have a picture of evolution that's missing but a few pieces yet the creationists steadfastly refuse to see the image and insist that we concentrate on the missing pieces.

[Hat Tip: Bad Astronomy]

Thursday, September 20, 2012

Boudry vs Plantinga

Alvin Plantinga is a famous philosopher who is widely respected and seems to be able to publish in all the right places. He is a theist (Calvinist) and for a long time he was at the University of Notre Dame in Indiana (USA). Since his retirement from there, he has taken a position at Calvin College.

Plantinga has long advocated the accommodationist position from the perspective of Christian apologetics. I bought his latest book, Where the Conflict Really Lies, because I'm interested in the conflict between science and religion.

I've been struggling for weeks with how to explain Plantinga's case. My problem was that I found the whole book quite ridiculous and it seemed to me that Plantina's idea of logic and rationality was much closer to kindergarten philosophy than to something one might expect from a distinguished scholar. I hesitated to say that out loud because it sounds very condescending coming from a scientist.

I had to be missing something. There must be some sophisticated philosophy in there somewhere and I just wasn't getting it. I couldn't post.

Are All IDiots Irony Deficient?

As I'm sure you can imagine, the Intelligent Design Creationists are delighted with the ENCODE publicity. This is a case where some expert scientists support one of their pet beliefs; namely, that there's no such thing as junk DNA. The IDiots tend not to talk about other expert evolutionary biologists who disagree with them—those experts are biased Darwinists or are part of a vast conspiracy to mislead the public.

You might think that distinguishing between these two types of expert scientists would be a real challenge and you would be right. Let's watch how David Klinghoffer manoeuvres through this logical minefield at: ENCODE Results Separate Science Advocates from Propagandists. He begins with ....
"I must say," observes an email correspondent of ours, who is also a biologist, "I'm getting a kick out of watching evolutionary biologists attack molecular biologists for 'hyping' the ENCODE results."

True, and equally enjoyable -- in the sense of confirming something you strongly suspected already -- is seeing the way the ENCODE news has drawn a bright line between voices in the science world that care about science and those that are more focussed on the politics of science, even as they profess otherwise.

Tuesday, September 18, 2012

Apocalypse in Ottawa!

The end is approaching. See you in Ottawa on November 30th!

Athena Andreadis Writes for Scientific American: Junk DNA, Junky PR

Quite a few science journalists have clued in to the fact that they were massively conned by the ENCODE publicity machine. Turns out that the death of junk DNA was greatly exaggerated.

Here's what Athena Andreadis has to say on the Scientific American website: Junk DNA, Junky PR. Athena is a professor in the Department of Cell and Developmental Biology at the University of Massachusetts Medical School.

Chris DiCarlo on the Sandwalk

My friend Chris DiCarlo recently visited Down House with his family. Here's a photo of him on the Sandwalk. Chris is a philosopher and it looks like he's trying very hard to strike a philosophical pose.

In fact, he just can't figure out which way to go to get out of there!

Chris joins a distinguished list of people whose visit to the Sandwalk has been recorded here.

Larry Moran
PZ Myers
John Wilkins
Ryan Gregory
The God Delusion
John Hawks
Michael Barton
Seanna Watson
Steve Watson
Michael Richards
Jeffrey Shallit
Chris DiCarlo

Priceless Idiot

UPDATE: The woman in the picture, Kim Stafford, was making fun of the Tea Party with this sign [Internet FAIL: The truth about that Tea Party sorority girl you saw on Facebook.

This photo is everywhere on the internet but it's so perfect that I just have to post it even though spelling is not one of my own strengths.

Monday, September 17, 2012

Stephen Jay Gould and Sydney Brenner Agree on Junk DNA

It's no secret that I'm a big fan of Stephen Jay Gould. I'm also a big fan of Sydney Brenner. Here's Gould writing in The Structure of Evolutionary Theory (pages 1269-1270). This is long and complicated but if you want to understand junk DNA and why it conflicts with Darwinism, then you've got to make the effort. I especially like the idea that Gould understands the difference between junk DNA, which can't be explained by any adaptive mechanism, and "selfish DNA," which isn't junk and has a Darwinian explanation. Many people don't get this.

Gould and Brenner are talking about repetitive DNA. This includes highly repetitive sequences of simple repeats and moderately repetitive sequences that include the transposons.

Gould on Darwinism and Nonadaptive Change

Some people have trouble understanding the difference between Darwinism and modern evolutionary theory.

In spite of the fact that he has been dead for a decade, Stephen Jay Gould remains the authority on challenges to classical Darwinism and the hardened version of the Modern Synthesis (sometimes referred to as Neo-Darwinism).

If you really want to understand this issue then you have to read The Structure of Evolutionary Theory. One of my criticism of those who would overthrow modern evolutionary theory is that they are often completely ignorant of the work done by Gould and his allies and they end up attacking a strawman version of modern evolutionary theory.

Gould described the essential features of Darwinism in many of his writings. The most important feature is an emphasis on natural selection as the mechanism of evolution. In much of his work Gould emphasizes the roles of contingency, constraints, and non-gradualistic evolution as extensions of Darwinism. However, he doesn't forget direct challenges to Darwinism in the form of nonadaptive mechanisms that don't, under any circumstances, fit within the Darwinian framework.

These are complicated issues and that partially explains why so many people have not been able to follow Gould's reasoning. He doesn't help by using a writing style that requires your full attention. The advantage of that style is that he doesn't dumb down the subject and he covers all the exceptions and qualifications.

Here's Gould explaining why some features could arise as one form of adaptation then shift to serve another adaptive role (functional shift) (page 1246-1247). These features are called exaptations since they did not originally arise as adaptation to their present role. (Think of a defective transposon that becomes a regulatory sequence.)
Nevertheless, also emphasized throughout, ... the basic concept of exaptation remains consistent with orthodox Darwinism (while expanding its purview and adding some structural clarification and sophistication) for an obvious reason: the principle of quirky functional shift does not challenge the control of evolution by natural selection as an adaptational process. Unpredictable shift of function may establish the ground of contingency, and may imply a rule for structural constraints upon phyletic pathways. But this principle does not undermine the functionalist basics of evolutionary change because features so effected remain adaptive throughout: they originate from one function (presumably by natural selection), and then undergo quirky shift to a different utility.

However, the principle of functional shift, ... implies a disarmingly simple and logical extension that does challenge the role of Darwinian mechanics and functionalist control over evolutionary change. Ironically, the very simplicity of the argument has often led to its dismissal as too obvious to hold any theoretical importance—a "feeling" that I shall try to refute in this section, and whose disproof represents an important step in the central logic of this book.

The deeper challenge posed to orthodox Darwinism by the principle of functional shift flows from the implication that, if current utility does not reveal the reasons for hisorical origin, then these initial reasons need not be adaptational or functional at all—for features with current adoptive status may have originated from nonadaptive reasons in an ancestral form. In other words, and in the terminology of table 11-1, when certain aptations rack rank as exaptations rather than adaptations, the coopted source will be identifiable as an ancestral structure with either adaptive origins (for a different function) or nonadaptive origins (for no function at all). ...

The general conclusion may be stated in a simple manner, but I believe that the resulting implications for evolutionary theory are both profound and curiously underappreciated: If many features that operate as adaptations under present regimes of natural selection were exapted from ancestral features with nonadaptive origins—and were not built as adaptations for their current use (or exapted from ancestral features with adaptive origins for different functions)—then we cannot explain all the pathways of evolutionary change under functionalist mechanics of the theory of natural selection. Instead, we must allow that many important (and currently adaptive) traits originated for nonadaptive reasons that cannot be attributed to the direct action of natural selection at all and, moreover, cannot be inferred from the exaptive utility of the trait in living species. Because the subject of evolutionary biology must engage many critical questions about the origins of features, and cannot be confined to the study of current utilities and selective regimes, nonadaptationist themes therefore assume an important role in a full account of life's history and the mechanisms of evolutionary change.
In other words, lots of things can't be explained by Darwinism even if they look adaptive today.

Monday's Molecule #186

Last week's molecules were the four common nuleosides in DNA [Monday's Molecule #185]. The winner was Matt Talarico.

This week I'm asking you to identify a complex structure made up of eight different components (top) plus one other (bottom). Name the structure making sure to be as specific as possible, Name the none components.

Post your answer as a comment. I'll hold off releasing any comments for 24 hours. The first one with the correct answer wins. I will only post mostly correct answers to avoid embarrassment. The winner will be treated to a free lunch.

There could be two winners. If the first correct answer isn't from an undergraduate student then I'll select a second winner from those undergraduates who post the correct answer. You will need to identify yourself as an undergraduate in order to win. (Put "undergraduate" at the bottom of your comment.)

Sunday, September 16, 2012

Read What Mike White Has to Say About ENCODE and Junk DNA

One of the good things to come out of this ENCODE/junk DNA fiasco is that I've discovered a number of excellent scientists who aren't afraid to speak out on behalf of science. One of them is Mike White, a systems biologist at the Center for Genome Sciences and Systems Biology, Washington Univ. School of Medicine, St. Louis (USA). He blogs at The Finch & Pea.

Mike published an impressive article on the Huffington Post a few days ago. This is a must-read for anyone interested in the controversy over junk DNA: A Genome-Sized Media Failure. Here's part of what he says ...
If you read anything that emerged from the ENCODE media blitz, you were probably told some version of the "junk DNA is debunked" story. It goes like this: When scientists realized that classical, protein-encoding genes make up less than 2% of the human genome, they simply assumed, in a fit of hubris, that the rest of our DNA was useless junk. (You might have also heard this from your high school or college teacher. Your teacher was wrong.) Along came the ENCODE consortium, which found that, far from being useless, junk DNA is packed with functionality. And so everything scientists thought they knew about the genome was wrong, wrong wrong.

The Washington Post headline read, "'Junk DNA' concept debunked by new analysis of human genome." The New York Times wrote that "The human genome is packed with at least four million gene switches that reside in bits of DNA that once were dismissed as 'junk' but that turn out to play critical roles in controlling how cells, organs and other tissues behave." Influenced by misleading press releases and statements by scientists, story after story suggested that debunking junk DNA was the main result of the ENCODE studies. These stories failed us all in three major ways: they distorted the science done before ENCODE, they obscured the real significance of the ENCODE project, and most crucially, they mislead the public on how science really works.

What you should really know about the concept of junk DNA is that, first, it was not based on what scientists didn't know, but rather on what they did know about the genome; and second, that concept has held up quite well, even in light of the ENCODE results.
Way to go, Mike!

In the past week, lot's of scientists have demonstrated that they don't know what they're talking about when they make statements about junk DNA. I don't expect any of those scientists to apologize for misleading the public. After all, their statements were born of ignorance and that same ignorance prevents them from learning the truth, even now.

However, I do expect lots of science journalists to write follow-up articles correcting the misinformation that they have propagated. That's their job.

Saturday, September 15, 2012

How Do Intelligent Design Creationists Define "Creationism"?

David Klinghoffer showed up in the comments on James Shapiro Claims Credit for Predicting That Junk DNA Is Actually Part of a "highly sophisticated information storage organelle" to ask about creationism.

He didn't like the fact that I define "creationism" as belief in a creator and anyone who believes in a creator is a creationist. I identified several flavors of creationism including Young Earth Creationism, Intelligent Design Creationism, and Theistic Evolution Creationism. This is exactly the same sort of definition used by many people and it's the one described in the Wikipedia article on creationism. (It has even more flavors.)

David Klinghoffer didn't like that so he decided to make an issue of it by posting on Evolution News & Views: What Is a "Creationist"? Let's take a look at what he says in order to learn a little more about the creationist mindset.

Friday, September 14, 2012

Does the Central Dogma Still Stand?

Lots of people don't understand the Central Dogma of Molecular Biology and that's probably why there are so many articles announcing its death. The article and book by James Shapiro is just one example [Revisiting the Central Dogma in the 21st Century].

The correct version of the Central Dogma of Molecular Biology is .... [see Basic Concepts: The Central Dogma of Molecular Biology]
... once (sequential) information has passed into protein it cannot get out again (F.H.C. Crick, 1958)

The central dogma of molecular biology deals with the detailed residue-by-residue transfer of sequential information. It states that such information cannot be transferred from protein to either protein or nucleic acid. (F.H.C. Crick, 1970)
Eugene Koonin has an article in Biology Direct entitled Does the central dogma still stand (Koonin, 2012).

Thursday, September 13, 2012

Groupthink Science And That 'Junk DNA'

The IDiots (e.g. Tom Bethell) over at Evolution News & Views are gloating about a comment made on The Wall Street Journal website [Why ENCODE Is a Significant Defeat for Darwinism].

The WSJ article is: Groupthink Science And That 'Junk DNA'.
Anyone with even the slightest understanding of the evolutionary process knows that evolution is too relentlessly efficient to have allowed most, or even large sections, of DNA to be "junk" ("'Junk DNA' Theory Debunked," U.S. News, Sept. 6). Any intelligent scientist would have simply said, "I don't know."

Unfortunately, this says something important about the quality of contemporary Ph.Ds. Groupthink has become pervasive in part because of how research is now financed: grants. The disillusioning sociological aspects of scientific research that Thomas Kuhn identified more than four decades ago have become more pronounced, not less.

Tom Shillock

Portland, Ore.
This is exactly backwards, in my opinion. The real problem is that many scientists think, incorrectly, that natural selection would have removed all junk DNA so they are looking for reasons why it isn't junk. If they can't find evidence then they just make up a story or re-define the word "function." They don't have even the slightest understanding of evolution, just like Tom Shillock.

UPDATE: Shapiro and Sternberg Anticipated the Fall of Junk DNA.

James Shapiro Claims Credit for Predicting That Junk DNA Is Actually Part of a "highly sophisticated information storage organelle"

Do you remember James Shaprio? He's the University of Chicago scientist who claims to have discovered a new theory of evolution in his book evolution: A View from the 21st Century [see my review in NCSE Reports]. The book criticizes the old hardened version of the Modern Synthesis and never mentions things like random genetic drift or Nearly-Neutral Theory. It's difficult to imagine how someone could criticize evolutionary theory without understanding population genetics but he managed to pull it off.

You might also recall that he's the scientist who criticized the Central Dogma of Molecular Biology when he clearly didn't understand it [Revisiting the Central Dogma in the 21st Century]. I was shocked to learn that he had published a paper with the title "Revisiting the Central Dogma in the 21st Century" without ever bothering to read the literature to find out how Francis Crick actually defined the Central Dogma. (In fact, Shapiro misrepresented Crick's view.) It goes to show you how silly you look when you criticize something you don't understand.

Tuesday, September 11, 2012

ENCODE/Junk DNA Fiasco: The IDiots Don't Like Me

Casey Luskin has devoted an entire post to discussing my views on junk DNA. I'm flattered. Read it at: What an Evolution Advocate's Response to the ENCODE Project Tells Us about the Evolution Debate.

Let's look at how the IDiots are responding to this publicity fiasco. Casey Luskin begins with ...
University of Toronto biochemistry professor Larry Moran is not happy with the results of the ENCODE project, which report evidence of "biochemical functions for 80% of the genome." Other evolution-defenders are trying to dismiss this paper as mere "hype".

Yes that's right -- we're supposed to ignore the intentionally unambiguous abstract of an 18-page Nature paper, the lead out of 30 other simultaneous papers from this project, co-authored by literally hundreds of leading scientists worldwide, because it's "hype." (Read the last two or so pages of the main Nature paper to see the uncommonly long list of international scientists who were involved with this project, and co-authored this paper.) Larry Moran and other vocal Internet evolution-activists are welcome to disagree and protest these conclusions, but it's clear that the consensus of molecular biologists -- people who actually study how the genome works -- now believe that the idea of "junk DNA" is essentially wrong.

ENCODE/Junk DNA Fiasco: John Timmer Gets It Right!

John Timmer is the science editor at Ars Technica. Yesterday he published the best analysis of the ENCODE/junk DNA fiasco that any science writer has published so far [Most of what you read was wrong: how press releases rewrote scientific history].

How did he manage to pull this off? It's not much of a secret. He knew what he was writing about and that gives him an unfair advantage over most other science journalists.

Let me show you what I mean. Here's John Timmer's profile on the Ars Technica website.
John is Ars Technica's science editor. He has a Bachelor of Arts in Biochemistry from Columbia University, and a Ph.D. in Molecular and Cell Biology from the University of California, Berkeley. John has done over a decade's worth of research in genetics and developmental biology at places like Cornell Medical College and the Memorial Sloan-Kettering Cancer Center. He's been a speaker at the annual meeting of the National Association of Science Writers and the Science Online meetings, and he's one of the organizers of the Science Online NYC discussion series. In addition to being Ars' science content wrangler, John still teaches at Cornell and does freelance writing, editing, and programming.
See what I mean? He has a degree in biochemistry and another one in molecular biology. People like that shouldn't be allowed to write about the ENCODE results because they might embarrass the scientists.

Monday, September 10, 2012

Monday's Molecule #185

Last week's molecule was warfarin, a rat poison with another role [Monday's Molecule #184]. The winner was Matt McFarlane.

This week we're in the middle of the ENCODE/junk DNA controversy. A dispute that reveals a serious lack of knowledge of fundamental concepts in biochemistry. I'm going to go back to basics today and ask you to name these four molecules. Be careful, I'm going to insist that you use the correct unambiguous names. Name them in order from upper left to upper right to lower left then lower right.

Post your answer as a comment. I'll hold off releasing any comments for 24 hours. The first one with the correct answer wins. I will only post mostly correct answers to avoid embarrassment. The winner will be treated to a free lunch.

There could be two winners. If the first correct answer isn't from an undergraduate student then I'll select a second winner from those undergraduates who post the correct answer. You will need to identify yourself as an undergraduate in order to win. (Put "undergraduate" at the bottom of your comment.)

Some past winners are from distant lands so their chances of taking up my offer of a free lunch are slim. (That's why I can afford to do this!)

In order to win you must post your correct name. Anonymous and pseudoanonymous commenters can't win the free lunch.

Winners will have to contact me by email to arrange a lunch date. Please try and beat the regular winners. Most of them live far away and I'll never get to take them to lunch. This makes me sad.

Comments are now open.

UPDATE: The molecules are deoxyadenosine, deoxyguanosine, deoxycytidine, deoxythymidine. This week's winner is Matt Talarico. Matt should contact me by email.

Nov. 2009: Jason Oakley, Alex Ling
Oct. 17: Bill Chaney, Roger Fan
Oct. 24: DK
Oct. 31: Joseph C. Somody
Nov. 7: Jason Oakley
Nov. 15: Thomas Ferraro, Vipulan Vigneswaran
Nov. 21: Vipulan Vigneswaran (honorary mention to Raul A. Félix de Sousa)
Nov. 28: Philip Rodger
Dec. 5: 凌嘉誠 (Alex Ling)
Dec. 12: Bill Chaney
Dec. 19: Joseph C. Somody
Jan. 9: Dima Klenchin
Jan. 23: David Schuller
Jan. 30: Peter Monaghan
Feb. 7: Thomas Ferraro, Charles Motraghi
Feb. 13: Joseph C. Somody
March 5: Albi Celaj
March 12: Bill Chaney, Raul A. Félix de Sousa
March 19: no winner
March 26: John Runnels, Raul A. Félix de Sousa
April 2: Sean Ridout
April 9: no winner
April 16: Raul A. Félix de Sousa
April 23: Dima Klenchin, Deena Allan
April 30: Sean Ridout
May 7: Matt McFarlane
May 14: no winner
May 21: no winner
May 29: Mike Hamilton, Dmitri Tchigvintsev
June 4: Bill Chaney, Matt McFarlane
June 18: Raul A. Félix de Sousa
June 25: Raul A. Félix de Sousa
July 2: Raul A. Félix de Sousa
July 16: Sean Ridout, William Grecia
July 23: Raul A. Félix de Sousa
July 30: Bill Chaney and Raul A. Félix de Sousa
Aug. 7: Raul A. Félix de Sousa
Aug. 13: Matt McFarlane
Aug. 20: Stephen Spiro
Aug. 27: Raul A. Félix de Sousa
Sept. 3: Matt McFarlane
Sept. 10: Matt Talarico

The Story of You: Encode and the human genome – video

This is really quite incredible. I don't think I've seen anything like it in my lifetime.

Two private for-profit companies, illumina and Nature, team up to promote the ENCODE results. They even suck in hire Tim Minchin to narrate it.

The average person watching this video will think that ENCODE is the best thing since sliced bread. The hype is astounding, and totally unjustified considering that we haven't learned anything of fundamental importance from the ENCODE project.

Is this what science is going to be like in the future—the person with the biggest advertising budget wins the scientific debate?

Science Writes Eulogy for Junk DNA

Elizabeth Pennisi is a science writer for Science, the premiere American science journal. She's been writing about "dark matter" for years focusing on how little we know about most of the human genome and ignoring all of the data that says it's mostly junk [see SCIENCE Questions: Why Do Humans Have So Few Genes? ].

It doesn't take much imagination to guess what Elizabeth Pennisi is going to write when she heard about the new ENCODE Data. Yep, you guessed it. She says that the ENCODE Project Writes Eulogy for Junk DNA.


Genomes & Junk DNA
Let's look at the opening paragraph in her "eulogy."
When researchers first sequenced the human genome, they were astonished by how few traditional genes encoding proteins were scattered along those 3 billion DNA bases. Instead of the expected 100,000 or more genes, the initial analyses found about 35,000 and that number has since been whittled down to about 21,000. In between were megabases of “junk,” or so it seemed.

Was ENCODE Worth It?

Michael Eisen is in a good position to ask whether the $200,000,000 spent on the ENCODE project was worth the money: Blinded by Big Science: The lesson I learned from ENCODE is that projects like ENCODE are not a good idea.

Here's part of what he says.
As I and many others have discussed, the media campaign around the recent ENCODE publications was, at best, unseemly. The empty and often misleading press releases and quotes from scientists were clearly masking the fact that, despite publishing 30 papers, they actually had very little of grand import to say, today, about what they found. The most pensive of them realized this, and went out of their way to emphasize that other people were already using the data, and that the true test was how much the data would be used over the coming years.
I'm not in a good position to judge whether the American investment was worthwhile but I can echo Michael Eisen's point about the importance of the data. We didn't learn anything new about the functional organization of the human genome. The conclusion that was most often attributed to the ENCODE result; namely, that almost all the genome is functional, is wrong.

I think this is a case where the misleading publicity campaign, aided and abetted by Nature and science journalists, has backfired. It has caused many people like Michael Eisen to question the value of ENCODE. Such questions might not have arisen if the consortium hadn't tried to put an improper spin on their results.

I feel sorry for the hundreds of graduate students, postdocs, and PI's involved in the consortium. The importance of their work, and the years of effort it took, are being overshadowed by the decision of a few leaders to make claims about it that don't hold up to scientific scrutiny.

Sunday, September 09, 2012

The Random Genome Project

Sean Eddy is a old—well not too old— fan. (Hi Sean!).

Because he's had all that training in how to think correctly, he gets the difference between junk DNA and functional DNA. Read his post at: ENCODE says what? (C'est what?).

Think about your answer to the Random Genome Project thought experiment.
So a-ha, there’s the real question. The experiment that I’d like to see is the Random Genome Project. Synthesize a hundred million base chromosome of entirely random DNA, and do an ENCODE project on that DNA. Place your bets: will it be transcribed? bound by DNA-binding proteins? chromatin marked?

Of course it will.

The Random Genome Project is the null hypothesis, an essential piece of understanding that would be lovely to have before we all fight about the interpretation of ENCODE data on genomes. For random DNA (not transposon-derived DNA, not coding, not regulatory), what’s our null expectation for all these “functional” ENCODE features, by chance alone, in random DNA?

(Hat tip to The Finch and Pea blog, a great blog that I hadn’t seen before the last few days, where you’ll find essentially the same idea.)

Washington Post: "‘Junk DNA’ concept debunked by new analysis of human genome"

The Washington Post is a highly respected newspaper read by millions. It is very influential, especially among politicians in Washington.

Here's what David Brown and Hristio Boytchev published a few days ago:
‘Junk DNA’ concept debunked by new analysis of human genome
Most of a person’s genetic risk for common diseases such as diabetes, asthma and hardening of the arteries appears to lie in the shadowy part of the human genome once disparaged as “junk DNA.”

Indeed, the vast majority of human DNA seems to be involved in maintaining individuals’ well being — a view radically at odds with what biologists have thought for the past three decades.

Those are among the key insights of a nine-year project to study the 97 percent of the human genome that’s not, strictly speaking, made up of genes.

The Encyclopedia of DNA Elements Project, nicknamed Encode, is the most comprehensive effort to make sense of the totality of the 3 billion nucleotides that are packed into our cells.

The project’s chief discovery is the identification of about 4 million sites involved in regulating gene activity. Previously, only a few thousand such sites were known. In all, at least 80 percent of the genome appears to be active at least sometime in our lives. Further research may reveal that virtually all of the DNA passed down from generation to generation has been kept for a reason.

“This concept of ‘junk DNA’ is really not accurate. It is an outdated metaphor,” said Richard Myers of the HudsonAlpha Institute for Biotechnology in Alabama.

Myers is one of the leaders of the project, involving more than 400 scientists at 32 institutions.

Another Encode leader, Ewan Birney of the European Bioinformatics Institute in Britain, said: “The genome is just alive with stuff. We just really didn’t realize that beforehand.”

“What I am sure of is that this is the science for this century,” he said. “In this century, we will be working out how humans are made from this instruction manual.”
This is wrong. Most of our genome is still junk in spite of what the ENCODE Consortium says.

Who is Richard Myers and where did he get the idea that the concept of junk DNA is an outdated metaphor? Does he have an explanation for all the evidence his statement refutes?

Here's the important question. Who is going to take responsibility for this PR fiasco?

Brendan Maher Writes About the ENCODE/Junk DNA Publicity Fiasco

Brendan Maher is a Feature Editor for Nature. He wrote a lengthy article for Nature when the ENCODE data was published on Sept. 5, 2012 [ENCODE: The human encyclopaedia]. Here's part of what he said,
After an initial pilot phase, ENCODE scientists started applying their methods to the entire genome in 2007. Now that phase has come to a close, signalled by the publication of 30 papers, in Nature, Genome Research and Genome Biology. The consortium has assigned some sort of function to roughly 80% of the genome, including more than 70,000 ‘promoter’ regions — the sites, just upstream of genes, where proteins bind to control gene expression — and nearly 400,000 ‘enhancer’ regions that regulate expression of distant genes.
I expect encyclopedias to be much more accurate than this.

As most people know by now, there are many of us who challenge the implication that 80% of the genome has a function (i.e it's not junk).1 We think the Consortium was not being very scientific by publicizing such a ridiculous claim.

The main point of Maher's article was that the ENCODE results reveal a huge network of regulatory elements controlling expression of the known genes. This is the same point made by the ENCODE researchers themselves. Here's how Brendan Maher expressed it.

The real fun starts when the various data sets are layered together. Experiments looking at histone modifications, for example, reveal patterns that correspond with the borders of the DNaseI-sensitive sites. Then researchers can add data showing exactly which transcription factors bind where, and when. The vast desert regions have now been populated with hundreds of thousands of features that contribute to gene regulation. And every cell type uses different combinations and permutations of these features to generate its unique biology. This richness helps to explain how relatively few protein-coding genes can provide the biological complexity necessary to grow and run a human being.
I think that much of this hype comes from a problem I've called The Deflated Ego Problem. It arises because many scientists were disappointed to discover that humans have about the same number of genes as many other species yet we are "obviously" much more complex than a mouse or a pine tree. There are many ways of solving this "problem." One of them is to postulate that humans have a much more sophisticated network of control elements in our genome. Of course, this ignores the fact that the genomes of mice and trees are not smaller than ours.

Ed Yong Updates His Post on the ENCODE Papers

For decades we've known that less than 2% of the human genome consists of exons and that protein encoding genes represent more than 20% of the genome. (Introns account for the difference between exons and genes.) [What's in Your Genome?]. There are about 20,500 protein-encoding genes in our genome and about 4,000 genes that encode functional RNAs for a total of about 25,000 genes [Humans Have Only 20,500 Protein-Encoding Genes]. That's a little less than the number predicted by knowledgeable scientists over four decades ago [False History and the Number of Genes]. The definition of "gene" is somewhat open-ended but, at the very least, a gene has to have a function [Must a Gene Have a Function?].

We've known about all kinds of noncoding DNA that's functional, including origins of replication, centromeres, genes for functional RNAs, telomeres, and regulatory DNA. Together these functional parts of the genome make up almost 10% of the total. (Most of the DNA giving rise to introns is junk in the sense that it is not serving any function.) The idea that all noncoding DNA is junk is a myth propagated by scientists (and journalists) who don't know their history.

We've known about the genetic load argument since 1968 and we've known about the C-Value "Paradox" and it's consequences since the early 1970's. We've known about pseudogenes and we've known that almost 50% of our genome is littered with dead transposons and bits of transposons. We've known that about 3% of our genome consists of highly repetitive DNA that is not transcribed or expressed in any way. Most of this DNA is functional and a lot of it is not included in the sequenced human genome [How Much of Our Genome Is Sequenced?]. All of this evidence indicates that most of our genome is junk. This conclusion is consistent with what we know about evolution and it's consistent with what we know about genome sizes and the C-Value "Paradox." It also helps us understand why there's no correlation between genome size and complexity.

Saturday, September 08, 2012

The Top American Science Questions: 2012

I'm really interested in science education and I'd love to see improvements so that we can begin to create a scientifically literate society. Although I'm not an American, I'm quite interested in the views of American politicians because they can have a huge influence on science education.

That's why I was looking forward to seeing what Barack Obama and Mitt Romney had to say about science. Do they personally believe in evolution? Do they understand that homeopathy is useless? Do they think that science conflicts with their religious beliefs? Do they personally believe that the universe began almost 14 billion years ago with a Big Bang? Do they understand what causes earthquakes? Can they tell us why the discovery of the Higgs boson was important? Do they know what a gene is? Can they personally tell us in a few sentences how an eclipse of the sun occurs? Do they understand the concept of a chemical reaction?

Friday, September 07, 2012

Zoë Goes to School

Sometimes you just have to post pictures of your granddaughter. Here's Zoë going off to her first day of "school" in Los Angeles.

She's two-and-a-half years old. She loved it.

Want more? Go to The Big Day.

At Least He Doesn't Call them IDiots!

I don't agree with everyhting Richard Dawkins says in this video but he's got the important parts right. Notice that he doesn't stoop to calling them IDiots, like I do. He uses other words.

Oh Dear. Another Non-Scientist Gets the Wrong Message from Ed Yong

David Ropeik identifies himself as an "international consultant in risk perception and risk communication, and an Instructor in the Environmental Management Program at the Harvard University Extension School." His blog is soapbox science on Nature Blogs.

Here's what part of what he posted today [A lesson from ENCODE about the limits on Human Reason].
In what should be another blow to the hubris of human intellect, we have a new entry in the long and ever growing list of “Really Big Things Scientists Believed” that turned out be wrong. This one is about DNA, that magical strand of just four amino acids, Adenine paired with Thymine, Cytosine paired with Guanine, millions of those A-T and C-G pairs linked together in various combinations to make the genes that spit out the blueprints for the proteins that make us. Or so science believed.

The problem was that, the ‘genes’ sections of DNA that coded for proteins only came to about 1.5% of the whole 2 meter-long strand. For decades molecular biologists didn’t know what the rest of the DNA…as in, nearly all of it…does. So, in a remarkable stroke of intellectual arrogance, they dismissed it as ‘junk’. Actually, the drier academics simply called it ‘non-coding DNA’. A Japanese scientist named Susumu Ohno called it junk, and the word stuck because, basically, scientists had no explanation for what most of DNA was for. So they assumed it was left over from evolution, had no current function, and was, literally, junk. As Francis Crick, one of the Nobel Prize winners for helping discover the structure of DNA, put it, non-coding DNA has “little specificity and conveys little or no selective advantage to the organism”. Right. As though nature would waste that much energy.

Well, there’s going to be a lot of editing on Wikipedia in the days and weeks to come, and it’s time to reprint the basic biology textbooks, because extensive research into the mystery of what most of DNA is doing there has discovered that the ‘junk’ isn’t junk at all. Most of it has all sorts of jobs. Science Journalist Ed Yong has written a wonderful summary of this work here.
As I said earlier, this is making my life very complicated. It's going to take a lot of effort to undo the damage caused by the ENCODE scientists and the science writers who fell for their scam.

At Last, Some Journalists Are Paying Attention!

From the Forbes website: Reports of Junk DNA's Demise Have Been Greatly Exaggerated by John Farrell.

Of course it's even more impressive because he quotes Ryan Gregory and me.

Still waiting to hear from the science writers who got it wrong the first time.

THIS Is What Michael Eisen Is Thinking!!!

Here's an excellent example of what's wrong with the way the ENCODE Consortium is interpreting their data. Congratulations to Michael Eisen! I wish I had said this: A neutral theory of molecular function.1

Read the whole thing very carefully and heed the lesson. Here's a excerpt,
I think a lot about Kimura, the neutral theory, and the salutary effects of clear null models every time I get involved in discussions about the function, or lack thereof, of biochemical events observed in genomics experiments, such as those triggered this week by publications from the ENCODE project.

It is easy to see the parallels between the way people talk about transcribed RNAs, protein-DNA interactions, DNase hypersensitive regions and what not, and the way people talked about sequence changes PK (pre Kimura). While many of the people carrying out RNA-seq, ChIP-seq, CLIP-seq, etc… have been indoctrinated with Kimura at some point in their careers, most seem unable to apply his lesson to their own work. The result is a field suffused with implicit or explicit thinking along the following lines:
I observed A bind to B. A would only have evolved to bind to B if it were doing something useful. Therefore the binding of A to B is “functional”.
One can understand the temptation to think this way. In the textbook view of molecular biology, everything is highly regulated. Genes are transcribed with a purpose. Transcription factors bind to DNA when they are regulating something. Kinases phosphorylate targets to alter their activity or sub-cellular location. And so on. Although there have always been lots of reasons to dismiss this way of thinking, until about a decade ago, this is what the scientific literature looked like. In the day where papers described single genes and single interactions, who would bother to publish a paper about a non-functional interaction they observed?

But experimental genomics blew this world of Mayberry molecular biology wide open. For example, when Mark Biggin and I started to do ChIP-chip experiments in Drosophila embryos, we found that factors were binding not just to their dozen or so non-targets, but the thousands, and in some cases tens of thousands of places across the genome. Having studied my Kimura, I just assumed that the vast majority of these interactions had evolved by chance – a natural, essential, consequence of the neutral fixation of nucleotide changes that happened to create transcription factor binding sites. And so I was shocked that almost everyone I talked to about this data assumed that every one of these binding events was doing something – we just hadn’t figured out what yet.


Rather than assuming – as so many of the ENCODE researchers apparently do – that the millions (or is it billions?) of molecular events they observe are a treasure trove of functional elements waiting to be understood, they should approach each and every one of them with Kimurian skepticism. We should never accept the existence or a molecule or the observation that it interacts with something as prima facia evidence that it is important. Rather we should assume that all such interactions are non-functional until proven otherwise, and develop better, compelling, ways to reject this null hypothesis.
Read the comments, especially the one from former colleague Chris Hogue on how to interpret phosphorylation of proteins and signal transduction. That's not going to be popular in my department!

I just have one small quibble with Michael's post. Not all textbooks describe the cell as if it were a finely tuned Swiss watch and not all textbooks take an adaptationist approach to evolution. Mine doesn't.

1. As a result of this post I've now relegated Jonathan Eisen to "brother of Michael Eisen" rather than the other way around. Sorry, Jonathan.

More Expert Opinion on Junk DNA from Scientists

The Nature issue containing the latest ENCODE Consortium papers also has a New & Views article called "Genomics: ENCODE explained" (Ecker et al., 2012). Some of these scientist comment on junk DNA.

For exampleshere's what Joseph Ecker says,
One of the more remarkable findings described in the consortium's 'entrée' paper is that 80% of the genome contains elements linked to biochemical functions, dispatching the widely held view that the human genome is mostly 'junk DNA'. The authors report that the space between genes is filled with enhancers (regulatory DNA elements), promoters (the sites at which DNA's transcription into RNA is initiated) and numerous previously overlooked regions that encode RNA transcripts that are not translated into proteins but might have regulatory roles.
And here's what Inês Barroso, says,
The vast majority of the human genome does not code for proteins and, until now, did not seem to contain defined gene-regulatory elements. Why evolution would maintain large amounts of 'useless' DNA had remained a mystery, and seemed wasteful. It turns out, however, that there are good reasons to keep this DNA. Results from the ENCODE project show that most of these stretches of DNA harbour regions that bind proteins and RNA molecules, bringing these into positions from which they cooperate with each other to regulate the function and level of expression of protein-coding genes. In addition, it seems that widespread transcription from non-coding DNA potentially acts as a reservoir for the creation of new functional molecules, such as regulatory RNAs.
If this were an undergraduate course I would ask for a show of hands in response to the question, "How many of you thought that there did not seem to be "defined gene-regulatory elements" in noncoding DNA?"

I would also ask, "How many of you have no idea how evolution could retain "useless" DNA in our genome?" Undergraduates who don't understand evolution should not graduate in a biological science program. It's too bad we don't have similar restrictions on senor scientists who write News & Views articles for Nature.

Jonathan Pritchard and Yoav Gilad write,
One of the great challenges in evolutionary biology is to understand how differences in DNA sequence between species determine differences in their phenotypes. Evolutionary change may occur both through changes in protein-coding sequences and through sequence changes that alter gene regulation.

There is growing recognition of the importance of this regulatory evolution, on the basis of numerous specific examples as well as on theoretical grounds. It has been argued that potentially adaptive changes to protein-coding sequences may often be prevented by natural selection because, even if they are beneficial in one cell type or tissue, they may be detrimental elsewhere in the organism. By contrast, because gene-regulatory sequences are frequently associated with temporally and spatially specific gene-expression patterns, changes in these regions may modify the function of only certain cell types at specific times, making it more likely that they will confer an evolutionary advantage.

However, until now there has been little information about which genomic regions have regulatory activity. The ENCODE project has provided a first draft of a 'parts list' of these regulatory elements, in a wide range of cell types, and moves us considerably closer to one of the key goals of genomics: understanding the functional roles (if any) of every position in the human genome.
The problem here is the hype. While it's true that the ENCODE project has produced massive amounts of data on transcription binding sites etc., it's a bit of an exaggeration to say that "until now there has been little information about which genomic regions have regulatory activity." Twenty-five years ago, my lab published some pretty precise information about the parts of the genome regulating activity of a mouse hsp70 gene. There have been thousands of other papers on the the subject of gene regulatory sequences since then. I think we actually have a pretty good understanding of gene regulation in eukaryotes. It's a model that seems to work well for most genes.

The real challenge from the ENCODE Consortium is that they question that understanding. They are proposing that huge amounts of the genome are devoted to fine-tuning the expression of most genes in a vast network of binding sites and small RNAs. That's not the picture we have developed over the past four decades. If true, it would not only mean that a lot less DNA is junk but it would also mean that the regulation of gene expression is fundamentally different than it is in E. coli.

[Image Credit: ScienceDaily: In Massive Genome Analysis ENCODE Data Suggests 'Gene' Redefinition.

Ecker, J.R., Bickmore, W.A., Barroso, I., Pritchard, J.K. (2012) Genomics: ENCODE explained. Nature 489:52-55. [doi:10.1038/489052a]
Yoav Gilad
& Eran Segal

Endogenous Retroviruses and Junk DNA

The latest version of the Carnival of Evolution pointed to an article by Steven Quistad on Small Things Considered. The article reviewed a recent paper on endogenous retroviruses [The Rise of Genomic Superspreaders].

Retroviruses are RNA viruses that go though a stage where their RNA genomes are copied into DNA by reverse transcriptase. The virus may integrate into the host genome and be carried along for many generations producing low levels of virus particles [Retrotransposons/Endogenous Retroviruses ]. Most of these events will occur in somatic cells so the integrated virus is not passed along to progeny but from time to time the virus integrates into germ line DNA and this is heritable.

There are 31 such events in our lineage, meaning that we have copies of 31 different retroviruses in our genome. The retroviruses may have produced copies in germ line DNA such that each of the 31 retroviruses is now represented by a family of sequences scattered throughout the genome. Today, these retrovirus sequences represent a total of 8% of our genome! That's over 200,000,000 base pairs of DNA. There are about 100 thousand different sites.1

There's no selective pressure to maintaining the functionality of these retrovirus sequences so, as you might have guessed, most of them have accumulated mutations over millions of years. (The original insertion events took place at various times ranging from 100 million years ago to only a few million years ago.) Almost all of the 8% consists of defective retrovirus sequences. It's junk.2

But it's a special kind of junk because retrovirus DNA has strong promoters that bind various transcription factors and the flanking enhancers ensure that the region around these promoters will be in open chromatin regions that have all the characteristics of real promoter sites. A substantial proportion of the defective retroviruses will still produce transcripts because the promoter region may not be mutated even though there may be lethal mutations elsewhere in the sequence.

What does this mean? It means that there will be thousands of junk DNA sites that bind transcription factors and RNA polymerase and may even be transcribed. When you're doing whole genome analyses, like those in the ENCODE study, you need to be careful to distinguish between functional promoters and non-functional promoters.

1. The typical retrovirus genome is about 3,000 bp in length but many of the defective retrotransposon sequences have been are truncated by deletions.

2. Except for an extremely small number that might have acquired a secondary function such as enhancing expression of a nearby gene.

Carnival of Evolution #51: Darwin's Restaurant

This month's Carnival of Evolution is hosted by The Stochastic Scientist, Kathy Orlinsky. Read it at: Carnival of Evolution 51: Darwin's Restaurant
Welcome to the 51st Carnival of Evolution, henceforth known as Darwin’s Restaurant. You may have noticed that the motto of my blog is ‘Science—there’s something for everyone.’ Well, that’s also true of evolution. Whether your passion is transitional fossils or reducible complexity, you’ll find something tasty on this menu.
There's some cool stuff this month.

The next Carnival of Evolution (September) will be hosted by The Genealogical World of Phyogenetic Networks. If you want to volunteer to host others, contact Bjørn Østman. Bjørn is always looking for someone to host the Carnival of Evolution. He would prefer someone who has not hosted before. Contact him at the Carnival of Evolution blog. You can send articles directly to him or you can submit your articles at Carnival of Evolution.

Eschaton 2012 Is Nigh!

CFI is sponsoring a conference in Ottawa (Ontario, Canada) on "Celebrating Reason at the End of the World." The title of the conference is Eschaton 2012. Go to the website to find out what "eschaton" means and how to pronounce it.

The meetings will take place from Friday Nov. 30 to Sunday Dec. 2 at a hotel in downtown Ottawa. The list of prominent speakers includes ...
  • PZ Myers (Biologist and author of the Pharyngula Blog)
  • Eugenie Scott (Executive Director of National Center for Science Education)
  • Ophelia Benson (Columnist for Free Inquiry magazine and author of Butterflies and Wheels Blog)
  • Christopher DiCarlo (Philosopher of Science and author of How to Become a Really Good Pain in the Ass
There's a whole bunch of less prominent speakers as well. My talk will be on Saturday morning. It's titled "Scientists vs IDiots."

Later on I'll be on a panel about science education with PZ Myers and Eugenie Scott. This should be lots of fun.

See you there! We'll eat poutine and beaver tails.

Thursday, September 06, 2012

You Just Knew This Was Coming, Didn't You?

Jonathan McLatchie must have hardly been able to contain himself when he wrote: Latest ENCODE Research Validates ID Predictions On Non-Coding Repertoire.
Readers will likely recall the ENCODE project, published in a series of papers in 2007, in which (among other interesting findings) it was discovered that, even though the vast majority of our DNA does not code for proteins, the human genome is nonetheless pervasively transcribed into mRNA. The science media and blogosphere is now abuzz with the latest published research from the ENCODE project, the most recent blow to the “junk DNA” paradigm. Since the majority of the genome being non-functional (as has been claimed by many, including notably Larry Moran, P.Z. Myers, Nick Matzke, Jerry Coyne, Kenneth Miller and Richard Dawkins) would be surprising given the hypothesis of design, ID proponents have long predicted that function will be identified for much of our DNA that was once considered to be useless. In a spectacular vindication of this hypothesis, six papers have been released in Nature, in addition to a further 24 papers in Genome Research and Genome Biology, plus six review articles in The Journal of Biological Chemistry.


This new research places a dagger through the heart of the junk DNA paradigm, and should give adherents to this out-dated assumption yet further cause for caution before they write off DNA, for which function has yet to be identified, as “junk".
Not much I can say right now. I'm up to my ears trying to convince sane people that the ENCODE papers are wrong. The IDiots are just going to have to wait.