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
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?
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.
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.
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.
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.)
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 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.
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.
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?
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.
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.
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.
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.
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.
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.
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.
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.
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.
Remember in high school or college, when you learned about all that DNA inside of you that was junk? The strings and strings of nonsense code that had no function? A recent blitz of papers from the ENCODE project have the world abuzz with news that would rip that idea apart.
But, like many things that stick around in text books long after science has moved on, the “junk DNA” idea that ENCODE disproved, didn’t really need disproving in the first place. Even in 1972, scientists recognized that just because we didn’t know what certain DNA regions did, didn’t make them junk.
They got their information from supposedly reputable scientists but that's not an excuse. It is the duty and responsibility of science journalists to be skeptical of what scientists say about their own work. In this particular case, the scientists are saying the same things that were thoroughly criticized in 2007 when the preliminary results were published.
I'm not letting the science journalists off the hook but I reserve my harshest criticism for the scientists, especially Ewan Birney who is the lead analysis coordinator for the project and who has taken on the role as spokesperson for the consortium. Unless other members of the consortium speak out, I'll assume they agree with Ewan Birney. They bear the same responsibility for what has happened.
The hundreds of researchers working on the ENCODE project have revealed that much of what has been called 'junk DNA' in the human genome is actually a massive control panel with millions of switches regulating the activity of our genes. Without these switches, genes would not work – and mutations in these regions might lead to human disease. The new information delivered by ENCODE is so comprehensive and complex that it has given rise to a new publishing model in which electronic documents and datasets are interconnected.
Here's the interesting thing. Many of us are upset about the press releases and the PR because we don't think the ENCODE data disproves junk DNA. Michael Eisen's perspective is entirely different. He's upset because, according to him, junk DNA was discredited years ago.
The problems start before the first line ends. As the authors undoubtedly know, nobody actually thinks that non-coding DNA is ‘junk’ any more. It’s an idea that pretty much only appears in the popular press, and then only when someone announces that they have debunked it. Which is fairly often. And has been for at least the past decade. So it is more than just intellectually lazy to start the story of ENCODE this way. It is dishonest – nobody can credibly claim this to be a finding of ENCODE. Indeed it was a clear sense of the importance of non-coding DNA that led to the ENCODE project in the first place. And yet, each of the dozens of news stories I read on this topic parroted this absurd talking point – falsely crediting ENCODE with overturning an idea that didn’t need to be overturned.
Eisen is wrong, junk DNA is alive and well. In fact almost 90% of our genome is junk.
ENCODE (ENcyclopedia Of DNA Elements) is a massive consortium of scientists dedicated to finding out what's in the human genome.
They published the results of a pilot study back in July 2007 (ENCODE, 2007) in which they analyzed a specific 1% of the human genome. That result suggested that much of our genome is transcribed at some time or another or in some cell type (pervasive transcription). The consortium also showed that the genome was littered with DNA binding sites that were frequently occupied by DNA binding proteins.
THEME
Genomes & Junk DNAAll of this suggested strongly that most of our genome has a function. However, in the actual paper the group was careful not to draw any firm conclusions.
... we also uncovered some surprises that challenge the current dogma on biological mechanisms. The generation of numerous intercalated transcripts spanning the majority of the genome has been repeatedly suggested, but this phenomenon has been met with mixed opinions about the biological importance of these transcripts. Our analyses of numerous orthogonal data sets firmly establish the presence of these transcripts, and thus the simple view of the genome as having a defined set of isolated loci transcribed independently does not seem to be accurate. Perhaps the genome encodes a network of transcripts, many of which are linked to protein-coding transcripts and to the majority of which we cannot (yet) assign a biological role. Our perspective of transcription and genes may have to evolve and also poses some interesting mechanistic questions. For example, how are splicing signals coordinated and used when there are so many overlapping primary transcripts? Similarly, to what extent does this reflect neutral turnover of reproducible transcripts with no biological role?
This didn't stop the hype. The results were widely interpreted as proof that most of our genome has a function and the result featured prominently in the creationist literature.
According to ENCODE’s analysis, 80 percent of the genome has a “biochemical function”. More on exactly what this means later, but the key point is: It’s not “junk”. Scientists have long recognised that some non-coding DNA probably has a function, and many solid examples have recently come to light. But, many maintained that much of these sequences were, indeed, junk. ENCODE says otherwise. “Almost every nucleotide is associated with a function of some sort or another, and we now know where they are, what binds to them, what their associations are, and more,” says Tom Gingeras, one of the study’s many senior scientists.
And what’s in the remaining 20 percent? Possibly not junk either, according to Ewan Birney, the project’s Lead Analysis Coordinator and self-described “cat-herder-in-chief”. He explains that ENCODE only (!) looked at 147 types of cells, and the human body has a few thousand. A given part of the genome might control a gene in one cell type, but not others. If every cell is included, functions may emerge for the phantom proportion. “It’s likely that 80 percent will go to 100 percent,” says Birney. “We don’t really have any large chunks of redundant DNA. This metaphor of junk isn’t that useful.”
The creationists are going to love this.
You blew it Ed Yong. Why didn't you ask him about the 50% of our genome containing DEFECTIVE transposons and the 2% that's pseudogenes, just for starters? Then you could ask him why he believes that all intron sequences (about 20% of our genome) are functional [What's in Your Genome?].
"Almost every nucleotide ..."? Gimme a break. Don't these guys read the scientific literature?
Methodological Naturalism is an a priori argument in favor limiting science to investigations of the natural world. It serves to protect religion from science since most religious questions are concerned with the supernatural and science, by fiat, isn’t allowed to ask those questions. Coincidentally, it also protects philosophy from science since metaphysical questions now become the exclusive domain of philosophy.
There are some philosophers who see through this house of cards but they are few and far between. It’s mostly scientists—and those who think like scientists—who say "What the heck are they talking about?"
Maarten Boudry, Stefaan Blancke, and Johan Braeckman from the Department of Philosphy at the University of Gent (Belgium) represent the heretics and dissenters among philosophers. If you want a summary of posts on this topic go to: Is Science Restricted to Methodologial Naturalism?. Here’s an excerpt from Grist to the Mill of Anti-evolutionism: The Failed Strategy of Ruling the Supernatural Out of Science by Philosophical Fiat (Boudry et al. 2012).
I began this discussion a few days ago by questioning the purpose of some common philosophical arguments. The example I selected concerned the claim that evolution is unguided. A prominent philosopher, Elliott Sober, tells us that even though there’s no evidence that evolution is guided it is still possible to imagine a supernatural being who could control evolution by tweaking molecules at the level of quantum mechanics. If this being was clever enough, and wanted to leave no trace of his activity, then one could imagine a situation where evolution was guided without anyone realizing it. Thus, theistic evolutionists need not despair because the scientific way of knowing can’t legitimately say that evolution is unguided.
Last week's molecule was raltitrexid, an anti-cancer drug [Monday's Molecule #183]. The winner was Raul A. Félix de Sousa. Raul has won ten times since I restarted Monday's Molecule last November.
This week's molecule is another strange-looking molecule with a very specific purpose. Identify the molecule and its role in mammals.
Post your answers 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 invisible for 24 hours. Comments are now open.
UPDATE: The molecule is warfarin or Coumadin®, a rat poison and an anticoagulant. It's a competitive inhibitor of vitamin K reductase and this blocks blood clotting. The winner is Matt McFarlane, one of the few people who can actually collect a free lunch. Please 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
I try really hard not to ban anyone from commenting on Sandwalk but there are some things I will not tolerate.
Someone named David Roemer recently tested the limits of my patience, and failed. He is now banned.
Here's what happened. I received an email message from David Roemer about a comment of his that did not appear on Sandwalk. I don't know why it didn't appear. I don't remember seeing it.
Shortly after receiving the email message I received a copy of a message David Roemer sent to the chair of my department. Here's the beginning ...
Dear Dr. XXX,
Prof. Moran, I believe, didn't approve of the following comment I made on his Sandwalk blog. He has every right to do so, but he has a moral duty not to coverup the misinformation contained in the AJP article I mention in my censored comment:
Natural selection only explains the adaptation of species to the environment. Not enough is known about the innovations natural selection acts upon to understand how mammals evolved from bacteria in only 3.5 billion years (common descent). The only theory that attempts to explain common descent is ID, but there is no evidence for ID.
IDiots try to make their theory look better by comparing it with natural selection. Atheists go along with this scam because they don’t want to admit that ID is a better theory than natural selection in some sense.
A corollary of the limitations of natural selection is that the second law of thermodynamics doesn’t apply to evolution, just as it doesn’t apply to the evolution of stars. Nevertheless, there is scientific literature about whether evolution violates the second law. Authors on the “does not” side argue that heat energy from the sun accounts for the increase in order (decrease in entropy). Heat, of course, tends to increase disorder.
This nonsense reached an extreme level in an article published by the American Journal of Physics (Entropy and evolution, Nov. 2008). This article actually calculates the entropy of the biosphere using the Boltzmann constant and an estimate of the thermodynamic probability of life. I’m trying to get the AJP to retract this absurd article.
I'm copying David Novak because he is on the Institute Board of First Things, which is refusing to publish my attached essay explaining why the AJP article is absurd. Both Novak and Moran are helping the AJP lie about evolution and thermodynamics.
My chair will be amused by this sort of thing. There's nothing he could do about it even if he wanted to.
This is one of the criteria for banning. Anyone who tries to get someone fired or reprimanded by going over their head to their employer will be banned. Anyone who harasses the family and friends of someone they disagree with will be banned. There are no exceptions.
I've also banned John Kwok for doing the same thing in an attempt to silence Jim Shapiro.
John starts his defense by explaining the correct use of "begging the question." I agree with him 100%. I hate it when people misuse this phrase by thinking it means "prompts me to ask the question."
But we expect better of the educated and cosmopolitan. It comes, therefore, as a continuing pain to me that scientists will often offer this piece of question beggary:
Science finds out things
Philosophy does not find out things the scientific way
Therefore philosophy is a waste of time and effort
The begged premise here is that only knowing things the scientific way is knowledge, or if the philosopher in question doesn’t say that knowledge is what philosophy offers, that only knowing things the scientific way is worthwhile. Some may even hint that only science delivers beauty, too.
It pains me to read this because I expect so much better of an educated and cosmopolitan Australian.
I'm not aware of any scientist who argues like this.
There was a time, not so long ago, when science and philosophy coexisted in (relative) peace and harmony. This began to change when science came under increasing attack from religion and from others who simply denied the knowledge that had been produced by the scientific way of thinking. (The latter group included advocates of parapsychology. The modern versions include those who deny climate change and those who think vaccinations cause autism. These groups are not necessarily religious.)
The rise of anti-scientism provoked a response from scientists, just as you might expect. Scientists began to speak out against the irrational claims of these science deniers. The counter-attack necessarily covered many people with strong religious beliefs. Gradually, many scientists came to the realization that the main problem was not the specifics of evolution or whether ESP could be tested. The real battleground was a war between rationalism and superstition. This led to a number of scientists coming out in support of atheism and focusing their attention on the flaws in religious thinking (i.e. superstition).
Now, you would think that philosophy would be a natural ally in this fight since the most important feature of philosophy is its ability to distinguish logical arguments from ones that are illogical. In other words, philosophy should be on the side of rationalism and not on the side of superstition.
I been watching proceedings at the Republican National Convention in Florida. If you think it's annoying for most liberal Americans, imagine what it's like for us furriners!
Coincidentally, we watched the last episode of The Newsroom a few days ago then decided to re-watch all ten episodes. It's one of the best shows on television. Makes me sad that The West Wing was cancelled. It's not a show that Republicans will enjoy.
Here's the clip from the first episode that sets the tone for a new kind of TV news show. The hero, Will McAvoy, is a cable news anchor who wants to tell it like it is instead of chasing ratings. The excerpt is from a town hall meeting at Northwestern University. A student has just asked why America is the greatest country in the world. (The student shows up again in Episode #10 when she wants to become a "greater fool.")
Not to be outdone, Ken Ham and the Creation Museum have taped a response ...
We are [responding to Nye] today with a video rebuttal featuring our “science guys” — Dr. David Menton and Dr. Georgia Purdom of our AiG and Creation Museum staff. These two PhD scientists were asked to reply to Mr. Nye, whose academic credentials do not come close to Drs. Menton and Purdom.
I present this for your amusement. I feel a bit sorry for Georgia Purdom since there's a high probability that some of her grandchildren are going to reject creationism. I wonder how she'll deal with that?
Tim Radford reviews The Selfish Gene by Richard Dawkins [The Selfish Gene by Richard Dawkins – book review]. The review is a bit late—the book was published in 1976—but I suppose the old adage of "better late than never" applies.
Actually it's not as bizarre as you might think. Lot's of people don't understand the ideas that Dawkins was pushing. He was mostly pointing out that evolution is a phenomenon that takes places at the level of genes and populations. Dawkins tweets that Rafford "gets it" in his review.
Lovely retrospective review of The Selfish Gene by Tim Radford, the Guardian's distinguished science writer. He gets it.
Jerry Coyne and I have been thinking along the same lines. We've been reading a lot of books by philosophers and reading their articles and blogs. We're exploring the idea that philosophy and science are different ways of knowing, as the philosophers want us to believe. We've taken to heart the criticism from our philosopher friends that scientists have to understand more about philosophy.
Jerry and I (and many others) have reached the tentative conclusion that much of what passes for modern philosophy is a house of cards. It doesn't tell us anything. It doesn't produce knowledge, or truth.
A few years ago my university (University of Toronto) decided to take a look at student evaluations. A committee was formed and this was its terms of reference.
In recognition of the need to periodically revisit practices related to the evaluation of teaching, the Course Evaluation Working Group was formed in the Fall 2009 (Appendix B) and was asked to:
Review current course evaluation practices across the University of Toronto and at peer institutions;
Review current research on course evaluation policies and practices;
If necessary, make recommendations to improve existing policies and practices.
This sounds like a good idea. As you know, I am very skeptical about student evaluations [On the Significance of Student Evaluations]. It's abut time that universities took a long hard look at the process with a view to abolishing student evaluations or drastically revising them and reviewing their importance in promotion and tenure decisions. It's even more important to revise the policy on using student evaluations to judge the effectiveness of part-time lecturers and teaching assistants. At the very least, their role in determining teaching awards should be critically examined.
If I were in charge of this project I would pick a committee composed almost entirely of the following groups:
front-line lecturers in introductory classes, including tenured faculty, untenured faculty, full-time lecturers, and part-time lecturers
teaching assistants (graduate students)
undergraduates
There would have to be substantial representation from undergraduates since they feel strongly about the issue and any drastic changes would require their consent and cooperation.
I would avoid having any administrators on the committee since the purpose of the committee was to evaluate existing university policy. In general, administrators are reluctant to make radical changes and they have trouble thinking outside the box. Furthermore, most of them don't have time to think seriously about the issue.
Edith Hillan (Vice-Provost, Faculty and Academic Life; Co-Chair)
Jill Matus (Vice-Provost, Students; Co-Chair)
Grant Allen (Vice-Dean, Undergraduate, Faculty of Applied Science and Engineering)
Gage Averill (Dean and Vice-Principal, Academic, UTM)
Cleo Boyd (Director, Robert Gilliespie Academic Skills Centre, UTM)
Corey Goldman (Associate Chair [Undergraduate], Department of Ecology & Evolutionary Biology, Faculty of Arts & Science)
Pam Gravestock (Associate Director, Centre for Teaching Support & Innovation)
Emily Greenleaf (Faculty Liaison & Research Associate, Centre for Teaching Support & Innovation)
Jodi Herold-McIlroy (Wilson Centre, Faculty of Medicine)
Glen Jones (Associate Dean, Academic, OISE) Helen Lasthiotakis (Director of Academic Programs and Policy)
Marden Paul (Director, Planning, Governance & Assessment)
Cheryl Regehr (Vice-Provost, Academic Programs)
Carol Rolheiser (Director, Centre for Teaching Support & Innovation)
Jay Rosenfield (Vice-Dean, Undergraduate Medical Education, Faculty of Medicine)
John Scherk (Vice-Dean, UTSC)
Elizabeth Smyth (Vice-Dean, Programs, School of Graduate Studies)
Suzanne Stevenson (Vice-Dean, Teaching & Learning, Faculty of Arts & Science)
No students. No teaching assistants. No part-time lecturers. Very few people who are currently teaching large undergraduate courses. Almost every person has an administrative positions of some sort—most of the positions take up a considerable portion of their time and some of them are full-time jobs.
That's what thinking like an administrator looks like.
I don't think my university is unusual. We have thousands of very smart students and teachers but all the important committees seem to be composed of people with heavy administrative responsibilities. Does anyone understand the logic here?
Maybe it's just my imagination, but I think I detect a change on Evolution News & View and on Uncommon Descent. For years these blogs have been attacking evolution without paying the least attention to what their opponents are saying. Lately, however, there seem to be some authors who are actually listening to their opponents and trying to address the main criticisms of the IDiot position.
Sometimes you even see articles that are close to being scientifically correct and I've even seen articles that recognize the existence of modern evolutionary theory (i.e. not Darwinism).
The good articles are still quite rare but I'm encouraged by the fact that they are listening.
The latest contribution is by Stephen A. Batzer, a contributor to Evolution News & Views since May 10, 2012. Batzer has a Ph.D. in Mechanical Engineering (see The Salem Conjecture). He's responding to an earlier post of mine where I attempted to explain to Casey Luskin why he was wrong about evolutionary theory [Is "Unguided" Part of Modern Evolutionary Theory?]. Recall that Luskin was saying that the "unguided" nature of evolution was a core part of the theory of Darwinian evolution.
The Flying Spaghetti Monster is all-powerful and all-knowing and she loves meatballs. She is also very sneaky and doesn't want to leave any evidence of her existence. That's why she's very careful to only steal meatballs that won't be missed. (How often do you count the meatballs in your spaghetti?).
As far as I know this is a perfectly valid philosophical argument. If you accept the premises then it's quite possible that meatballs are disappearing from kitchens and restaurants without us ever being aware of the problem.
I'm not a philosopher but I strongly suspect that there aren't any papers on the possible existence of the Flying Spaghetti Monster in the philosophical literature. I doubt that there are any Ph.D. theses on the topic.
Last week's molecule was a small protein machine that pumps protons across a membrane (ubiquinol:cytochrome c oxidoreductase) [Monday's Molecule #182]. The winner was Stephen Spiro. I think he's a student at the University of Toronto (UT) but it's a campus I haven't heard of in a place called "Dallas."
This week's molecule is a lot less complicated although it's rather strange looking. This molecule has a very specific use. Name the molecule—the common name will do—and describe its use.
Post your answers 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 invisible for 24 hours. Comments are now open.
UPDATE: The molecule is raltitrexed, also known as Tomudex. It's an inhibitor of the enzyme thymidylate synthase, the enzyme responsible for converting dUMP to dTMP. The drug is effective as an anti-cancer agent since it prevents cell division by blocking DNA synthesis. The winner is Raul A. Félix de Sousa (again).
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
