A lot of the debate over ENCODE's publicity campaign concerns the meaning of the word "function." In the summary article published in Nature last September the authors said, "These data enabled us to assign biochemical functions for 80% of the genome ...." (The ENCODE Project Consortium, 2012).
Here's how they describe function.
Operationally, we define a functional element as a discrete genome segment that encodes a defined product (for example, protein or non-coding RNA) or displays a reproducible biochemical signature (for example, protein binding, or a specific chromatin structure).
What, exactly, do the ENCODE scientists mean? Do they think that junk DNA might contain "functional elements"? If so, that doesn't make a lot of sense, does it?
Ewan Birney tried to address this definitional morass on his blog [ENCODE: My own thoughts] where he says ....
It’s clear that 80% of the genome has a specific biochemical activity – whatever that might be. This question hinges on the word “functional” so let’s try to tackle this first. Like many English language words, “functional” is a very useful but context-dependent word. Does a “functional element” in the genome mean something that changes a biochemical property of the cell (i.e., if the sequence was not here, the biochemistry would be different) or is it something that changes a phenotypically observable trait that affects the whole organism? At their limits (considering all the biochemical activities being a phenotype), these two definitions merge. Having spent a long time thinking about and discussing this, not a single definition of “functional” works for all conversations. We have to be precise about the context. Pragmatically, in ENCODE we define our criteria as “specific biochemical activity” – for example, an assay that identifies a series of bases. This is not the entire genome (so, for example, things like “having a phosphodiester bond” would not qualify). We then subset this into different classes of assay; in decreasing order of coverage these are: RNA, “broad” histone modifications, “narrow” histone modifications, DNaseI hypersensitive sites, Transcription Factor ChIP-seq peaks, DNaseI Footprints, Transcription Factor bound motifs, and finally Exons.
That's about as clear as mud.
We all know what the problem is. It's whether all binding sites have a biological function or whether many of them are just noise arising as a property of DNA binding proteins. It's whether all transcripts have a biological function or whether many of those detected by ENCODE are just spurious transcripts or junk RNA. These questions were debated extensively when the ENCODE pilot project was published in 2007. Every ENCODE scientist should know about this problem so you might expect that they would take steps to distinguish between real biological function and nonfunctional noise.
Their definition of "function" is not helpful. In fact, it seems deliberately designed to obfuscate.
Let's see how other scientist interpret the ENCODE results. In a News & Views article published in Nature last September, Joseph R, Ecker (Salk Institute scientist) said ...
One of the more remarkable findings described in the consortium's 'entré' paper is that 80% of the genome contains elements linked to biochemical function, dispatching the widely held view that the human genome is mostly 'junk DNA.'
That makes at least one genomics worker who thinks that "biochemical function" and junk DNA are mutually exclusive.
Q1: Does GENCODE believe that 80% of the genome is functional?
As noted, we will only discuss here the portion of the genome that is transcribed. According to the main ENCODE paper, while 80% of the genome appears to have some biological activity, only “62% of genomic bases are reproducibly represented in sequenced long (>200 nucleotides) RNA molecules or GENCODE exons”. In fact, only 5.5% of this transcription overlaps with GENCODE exons. So we have two things here: existing GENCODE models largely based on mRNA / EST evidence, and novel transcripts inferred from RNAseq data. The suggestion, then, is that there is extensive transcription occurring outside of currently annotated GENCODE exons.
There's another scientist who thinks that 80% of the genome has some biological activity in spite of the fact that the ENCODE paper says it has "biochemical function." I don't think "biological activity" is compatible with "junk DNA," but who knows what they think?
Since this person is part of the ENCODE team, we can assume that at least some of the scientists on the team are confused.
The Sanger Institute (Cambridge, UK) was an important player in the ENCODE Consortium. It put out a press release on the day the papers were published [Google Earth of Biomedical Research]. The opening paragraph is ...
The ENCODE Project, today, announces that most of what was previously considered as 'junk DNA' in the human genome is actually functional. The ENCODE Project has found that 80 per cent of the human genome sequence is linked to biological function.
It looks like the Sanger Institute equates "biochemical function" and "biological function" and it looks like neither one is compatible with junk DNA.
I think the ENCODE leaders, including Ewan Birney, knew exactly what they were doing when they defined function. They meant "biological function" even though they equivocated by saying "biochemical function." And they meant for this to be interpreted as "not junk" even though they are attempting to backtrack in the face of criticism.
Function Wars
(My personal view of the meaning of function is described at the end of Part V.)
The ENCODE Project Consortium (2012) An integrated encyclopedia of DNA elements in the human genome. Nature 489: 57-74. (E. Birney, corresponding author)
There are now been four papers in the scientific literature criticizing the way ENCODE leaders hyped their data by claiming that most of our genome is functional [see Ford Doolittle's Critique of ENCODE ]. There have been dozens of blog postings on the same topic.
The worst of the papers were published by Nature—this includes the abominable summary that should never have made it past peer review (Encode Consortium, 2012).
The lead editor on the ENCODE story was Brendan Maher and he promoted the idea that the ENCODE results showed that most of our genome has a function [ENCODE: The human encyclopaedia]
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.
Evolutionary change that occurs by random sampling of different alleles from one generation to the next. This causes nonadaptive evolutionary change.
Jerry Coyne
"Why Evolution Is True"There seem to be two important themes in the current pedagogical literature on science education. One of them is about student-centered learning—a concept I think we should all adopt. The other is about student misconceptions and how to deal with them. Much of the literature suggests that misconceptions need to be confronted and corrected. They can't be corrected by simply presenting the "correct" information. You need to actually address the misconception and show why it is wrong. This is a form of "teach the controversy" and that's not going to sit well with many American supporters of evolution.
Here's an interesting paper on "Biology Undergraduates’ Misconceptions about Genetic Drift" (Andrews et al., 2012). The abstract covers all the important points.
Theist: You say there is no God. Evolutionary Materialist [EM]: Yes. Theist: Yet belief in God among many (if not most) humans persists. EM: I cannot deny that. Theist: How do you explain that? EM: Religious belief is an evolutionary adaption. Theist: But you say religious belief is false. EM: That’s correct. Theist: Let me get this straight. According to you, religious belief has at least two characterizes: (1) it is false; and (2) evolution selected for it. EM [looking a little pale now, because he’s just figured out where this is going]: Correct. Theist: You believe the Neo-Darwinian Synthesis [NDS] is true. EM: Of course. Theist: How do you know your belief in NDS is not another false belief that evolution has selected for? EM: ___________________
Our materialist friends are invited to fill in the blank.
This is the fourth paper that's critical of the ENCODE hype. The first was Sean Eddy's paper in Current Biology (Eddy, 2012). The second was a paper by Niu and Jiang (2012), and the third was a paper by Graur et al. (2013). In my experience this is unusual since the critiques are all directed at how the ENCODE Consortium interpreted their data and how they misled the scientific community (and the general public) by exaggerating their results. Those kind of criticisms are common in journal clubs and, certainly, in the blogosphere, but scientific journals generally don't publish them. It's okay to refute the data (as in the arsenic affair) but ideas usually get a free pass no matter how stupid they are.
In this case, the ENCODE Consortium did such a bad job of describing their data that journals had to pay attention. (It helps that much of the criticism is directed at Nature and Science because the other journals want to take down the leaders!)
Read the following statement from the Wikipedia article on the Genetic Code.
... the genetic code used by all known forms of life is nearly universal with few minor variations. This suggests that a single evolutionary history underlies the origin of the genetic code.
What wrong with this statement? Cornelius Hunter says that the statement "... is false—at least from a scientific perspective" [Here is Why the DNA Code is a Problem]. Can you guess why this IDiot would make such a claim?
It has been repeatedly proposed to expand the scope for SETI, and one of the suggested alternatives to radio is the biological media. Genomic DNA is already used on Earth to store non-biological information. Though smaller in capacity, but stronger in noise immunity is the genetic code. The code is a flexible mapping between codons and amino acids, and this flexibility allows modifying the code artificially. But once fixed, the code might stay unchanged over cosmological timescales; in fact, it is the most durable construct known. Therefore it represents an exceptionally reliable storage for an intelligent signature, if that conforms to biological and thermodynamic requirements. As the actual scenario for the origin of terrestrial life is far from being settled, the proposal that it might have been seeded intentionally cannot be ruled out. A statistically strong intelligent-like “signal” in the genetic code is then a testable consequence of such scenario. Here we show that the terrestrial code displays a thorough precision-type orderliness matching the criteria to be considered an informational signal. Simple arrangements of the code reveal an ensemble of arithmetical and ideographical patterns of the same symbolic language. Accurate and systematic, these underlying patterns appear as a product of precision logic and nontrivial computing rather than of stochastic processes (the null hypothesis that they are due to chance coupled with presumable evolutionary pathways is rejected with P-value < 10–13). The patterns display readily recognizable hallmarks of artificiality, among which are the symbol of zero, the privileged decimal syntax and semantical symmetries. Besides, extraction of the signal involves logically straightforward but abstract operations, making the patterns essentially irreducible to natural origin. Plausible ways of embedding the signal into the code and possible interpretation of its content are discussed. Overall, while the code is nearly optimized biologically, its limited capacity is used extremely efficiently to pass non-biological information.
According to Uncommon Descent, the article is written by two scientists. They turn out to be two mathematicians from the Republic of Kazakhstan [The “Wow! signal” of the terrestrial genetic code].
Can you guess why the IDiots would believe such a ridiculous claim?
I wonder if Cornelius Hunter thinks this is science?
The last "Monday's Molecule" was phycoerythrin [Monday's Molecule #198]. The winner was Piotr Gasiorowski.
This week's molecule can do some very bad things to certain cells. You just have to give the common name and briefly explain what it does and how it works.
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.)
The first talk was quite private and it was not recorded. The second talk, on a Thursday evening, was in one of the main lecture theaters in my building. There were at least 400 people in the audience. This talk was on the "Limits of Darwinism" and it was recorded. You can watch it in the video below.
Imagine a typical1 citizen of a country in Western Europe. She doesn't believe in god(s) and neither did her parents or grandparents. How should she feel? Should she be depressed and overcome with a sense of hopelessness because there are no god(s) to save her?
Yes, according to Damon Linker who recently reviewed a book by A.C. Grayling [Where are the honest atheists? ]. The subtitle is: "That godlessness might be both true and terrible is something that the new atheists refuse to entertain."
Hmmm ... he's right about that. I haven't entertained the notion that not believing in imaginary beings might be "terrible." Why should I? Here's his answer ...
Jonathan Eisen is becoming one of my favorite bloggers. He alerts us to a horrible press release published recently by the National Science Foundation (USA):How to Thrive in Battery Acid and Among Toxic Metals.
It talks about a strain of red algae called Galdieria sulphuraria that has apparently inherited many genes from bacteria by lateral gene transfer. Here's how the press release hypes the result ...
The scientists made an unexpected discovery: Galdieria's genome shows clear signs of borrowing genes from its neighbors.
Many genes that contribute to Galdieria's adaptations were not inherited from its ancestor red algae, but were acquired from bacteria or archaebacteria.
This "horizontal gene transfer" is typical for the evolution of bacteria, researchers say.
However, Galdieria is the first known organism with a nucleus (called a eukaryote) that has adapted to extreme environments based on horizontal gene transfer.
"The age of comparative genome sequencing began only slightly more than a decade ago, and revealed a new mechanism of evolution--horizontal gene transfer--that would not have been discovered any other way," says Matt Kane, program director in the National Science Foundation's (NSF) Division of Environmental Biology, which funded the research.
"This finding extends our understanding of the role that this mechanism plays in evolution to eukaryotic microorganisms."
Galdieria's heat tolerance seems to come from genes that exist in hundreds of copies in its genome, all descending from a single gene the alga copied millions of years ago from an archaebacterium.
"The results give us new insights into evolution," Schoenknecht says. "Before this, there was not much indication that eukaryotes acquire genes from bacteria."
A "new mechanism of evolution" that was only revealed a decade ago by genome sequencing? Jonathan Eisen explains why this is so very wrong. You should read his post: Ugg - story about gene transfer/evolution based on NSF press release has a NASA-esque smell. I agree 100%. We've got to put and end to this kind of ridiculous hype and misrepresentation. It's damaging to science.1
The published results are interpreted as novel but only in the sense that the genes acquired from bacteria are (presumably) directly related to enhanced fitness (Schönknecht et al., 2013). Here's what the authors say in the paper.
Eukaryotic innovations usually arise through gene duplications and neofunctionalizations, which lead to expansion of existing gene families (8). In contrast, archaea and bacteria commonly adapt through horizontal gene transfer (HGT) from other lineages (9). HGT has also been observed in some unicellular eukaryotes (10); however, to our knowledge, horizontally acquired genes have not been linked to fitness-relevant traits in free-living eukaryotes
That point is reiterated in the summary.
These findings for G. sulphuraria mirror the results of a previous systematic study, which showed that proteobacterial adaptation relies on the horizontal acquisition of genes that function at the bacteria's interface to the environment (19). Whereas the importance of HGT for evolution of Bacteria and Archaea is well established, adaptation of a eukaryotic extremophile by gene transfer from Bacteria and Archaea is unexpected and shines a new light on the evolution of unicellular eukaryotes.
There's nothing about a new mechanism of evolution in the actual paper.
John Witton doesn't know much about biochemistry, genetics, or evolution but he's willing to learn. He will pay you $1000 (US) if you can answer any one of the six questions he has posed. He made this offer in the comments to my post: Saturday, February 28, 1953.
Here's what he said ...
I have been known to cause some problems on other forums, for obvious reasons, but I had hoped that on this forum we will be able to get to the bottom of the problems such as" vitalism vs entropy barrier, self assembly of proteins, self-cell membrane formation, metabolism first vs RNA world, why did evolution need 600 types of mangoes and how did they evolve and why?
Why did Larry Moran and Craig Venter evolve to baldness only on the part of the scalp but they have retained their bushy hair on the side and lower back of their scalp????
For those who answer one of these question logically, I am willing to pay $1000.00
I offered to answer two questions; the one on self assembly of proteins and the one on why male pattern baldness evolved. I suggested that John Witton could send the check to a neutral third party and that we could agree on a judge who would decide whether I had answered the questions satisfactorily. I recommended Michael Behe as the judge for the first question and Michael Denton as the judge for the second question.
John Witton agreed. On Saturday, March 2, 2013, he said ...
I’m glad you took the bait Larry…for the lack of better word in English… You are not a very good bluffer though…I’m hoping you don’t play poker and bet large sums of money… Anyway, even though you are paddling back from some of the issues I have presented you know you can’t explain, I’m still going to pursue this transaction, since I can still nail you on those two issues you feel comfortable with…You have nothing to lose...or it might be a little bit of pride, which is fine with me… So, this is what I’m doing. I am sending two cheques $1000.00 US each to Michael Behe and Michael Denton with the explanation of our agreement. They may not like writing extensive explanation as to their judgment or nothing at all, except Larry or John is the winner in their view. We just have to accept that.
Then on Monday he said ...
I have contacted both Behe and Denton. I have emailed the Discovery Institute regarding our arraignment. Even The Star is interested, if Behe participates... I don't think anybody takes you seriously Larry... We'll see.. You seem to be a big mouth that writes text books nobody understands, even you ...;)
I checked with Michael Behe on Thursday but he still had not heard from John Witton. I wasn't able to find out how to contact Michael Denton ... I'm waiting for Witton to send me the contact information since he already got in touch. (If anyone has an email address please send it to me.)
As it turns out. Witton had the stomach flu so he didn't send the checks. I'm sure he'll send them as soon as he feels better. (Apparently the flu strain comes from Canada!)
Larry is right. I have not sent the cheques or the paper to Behe or Denton yet... I'm sick with a bad case of stomach flu...You don't have to believe me... I will try to contact you when I'm better...Sorry to all my supporters...
According to Witton he now "got Larry by the balls." I thought I should let all my enemies know about this so they can watch the spectacle. Some Sandwalk readers might want to help John by answering one of the other questions for $1000.
While we're waiting for John Witton to keep his word, you might enjoy this video of Robert Shapiro (not John Witton) questioning the work on the origin of life. It was posted by John Witton so presumably he likes it.
Last Sunday (March 3, 2013) CBC radio aired a discussion on "Does religion have a place in public life?" The host was Rex Murphy. You can listen to the entire thing at: Does religion have a place in public life?.
I want to draw your attention to a segment where former Canadian Senator Pat Carny talks about her esperience with atheists. (Carney was a cabinet minister under Prime Minister Brian Mulroney.) The excerpt is embedded below. If it doesn't work, click on Pat Carney MP3.
Here how she begins ...
... you're debating the wrong question. It's not the role of religion in public institutions. it's the difficulty of being a person of faith working with people who haven't any ... any religion. And I'm speaking as someone with 27 years in parliament ...
It gets worse. She claims that atheists simply don't share her values, such as the Golden Rule, therefore you can't find common ground when trying to make policy.
All I can say is that it's a damn good thing she doesn't live in Western Europe because those secular societies clearly don't exhibit any of the values she holds so dear.
[Hat Tip: Thanks to Tony Burns for preparing the audio excerpt.]
Friday night, after cutting out the cardboard bases, still deep in defeat Watson went home and then to the theatre. Saturday morning, February 28, he came in, cleared a place to work, got out his cardboard cutouts.
Though I initially went back to my like-with-like prejudices, I saw all too all too well that they led nowhere. When Jerry [Donohue] came in I looked up, saw that it was not Francis, and begin shifting the bases in and out of various other pairing possibilities. Suddenly I became aware that an adenine-thymine pair held together by two hydrogen bonds was identical in shape to a guanine-cytosine pair held together by at least two hydrogen bonds. All the hydrogen bonds seem to form naturally; no fudging was required to make the two types of base pair identical in shape.1
Watson stumbled into this part of the solution visually, from a shape, a representation, and that had happened several times before; that is the way his mind works. Note two of the four kinds of bases have the same contour. Watson found that the purine adenine, a fused double ring with other atoms fringing it at several points, could form two hydrogen bonds with the pyrimidine thymine, a single ring, when he placed the two cutouts side by side in the right way. The bond were the correct length, and were straight lines, N—H--O or N--H—N, as Pauling's model-building precepts required. Guanine and cytosine made hydrogen bonds the same way. The pairing could not be switched, however, for then the various atoms around the fringes got in each other's way. But when an A-T pair was laid on top of a G-C pair, the two compound shapes were exactly congruent. Such pairs could fit inside the backbones without bulges or pinches. Donahue said these pairs agreed with what he knew. Crick, when he came in, immediately pointed out that the way the bases in these pairs would attach to their sugars meant that the two backbones ran in opposite directions, just as they had to do. Each chain could include both purines and pyrimidines, with pairs flipped over. That satisfied the dyadic symmetry. Chargaff's ratios were satisfied, too. The bases could appear in any order on one chain. Once that order was fixed, though, the base pairing, guanine always with cytosine and adenine with thymine, determined a complementary order on the opposite chain. That morning, Watson and Crick knew, although still in mind only, the entire structure: it had emerged from the shadow of billions of years, absolute and simple, and was seen and understood for the first time. Twenty angstrom units in diameter, seventy-none billionths of an inch. Two chains twinning coaxially, clockwise, one up the other down, a complete turn the screw in 34 angstroms. The bases flat in their pairs in the middle, 3.4 angstroms and a tenth of a revolution separating a pair from the one above or below. The chains held by the pairing closer to each other around the circumference one way than the other, by an eighth of a turn, one groove up the outside narrow, the other wide. A melody for the eye of the intellect, not a note wasted. In itself, physically, structure carried the means of replication—positive to negative, complementary. As the strands unwound, at double template was there in the base pairing, so that only complementary nucleotides could form bonds and drop into place as the daughter strands grew. ... one doubts, of course, that Crick and Watson altogether realized, that morning, what they had seen. "We have discovered the secret of life," Crick told everyone within earshot over drinks that noon at the Eagle. It was not the entire secret of life, yet truly for the first time at the ultimate biological level structure had become one with function, the antimony dialectically resolved. The structure of DNA is flawlessly beautiful. Horace Freeland Judson The Eighth Day of Creation Expanded edition 1996, pp. 148-150 Cold Spring Harbor Laboratory Press
The Big Island (Hawaii) is one giant pile of lava from five different volcanoes. The large one, slightly below center in the photo, is Mauna Loa and it is still an active volcano. You can see streaks of old lava flows spreading out from the summit. Mauna Kea, the slightly higher volcano above center, is now dormant.1 The active volcano that tourist visit is Kilauea, below and to the right on Mauna Lao.
This is the dry side of the island and the surrounding area is very desert-like. As you can see from the photo I took (below), the resort area is not desert at all. That lush vegetation requires constant watering. (I don't know were the water comes from.) You can also see the parts of the lava flow that have not been transformed. It's very impressive to see it up close.
The photos are from the balcony of our apartment. When we woke up today there was snow on the top of the mountain. The temperature here is about 30°C (or 86°F for the only major country that isn't metric.2)
[Hat Tip: Ms. Sandwalk took the photos of snow-capped Mauna Loa with her telephoto lens.
1. That's where the Hawaiian observatories are located.
2. Liberia and Burma are the other two countries that aren't metric.
This is a view of Wakiki Beach in Honolulu, Hawaii. I took it from LuLu's Surf Club where I was eating fish tacos and drinking Hawaiian beer. (The fish tacos were horrible. The beer was acceptable.)
I took a few more photos of the beach while we were strolling along the path behind the beach. It was a beautiful day with temperatures hovering around 28°. We stayed in a hotel a few blocks away 'cause we couldn't afford the big hotels that were right on the beach.
A lot of the debate over ENCODE's publicity campaign concerns the meaning of the word "function." In the summary article published in Nature last September the authors said, "These data enabled us to assign biochemical functions for 80% of the genome ...." (The ENCODE Project Consortium, 2012). 
