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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.

Winners
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.

THEME

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—talk.origins 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.