Haught vs Coyne: The Q&A

Here's an excellent summary of the Q&A from the debate. It's from Eric MacDonald at Choice in Dying: Q&A: Haught on God: Bitter, Impolite and Wrong.

He has a blow-by-blow account of the questions and answers following the debate but I especially like this ....

The assumption that science decided to leave out questions of god, meaning, purpose and value is a caricature of the history of science, and Haught, who claims to be making a serious attempt to show the compatibility of science and religion, must know this. If he doesn’t, and he really thinks that science made such a decision — how does “science” do this, by the way? — then his misunderstanding of the relation of science and religion is total.

When Haught turns around, then, and castigates Jerry by saying that everything that he said was a caricature, that every quotation that Jerry took from Haught’s work was taken out of context, and that instead of reading carefully and thoughtfully Jerry got his idea of god and theology from creationist websites, this was undoubtedly the most aggressive and impolite move of the whole debate. Listen to what he says:

Remember that John Haught is a Roman Catholic theologian. As far as I know he has never dissociated himself from the main teachings of the Roman Catholic Church. If he doesn't believe in any of the stuff that Jerry mentioned then isn't it up to him (Haught) to clarify what he does believe in?

Does he believe in the resurrection? Does he believe that humans have souls? Does he believe in miracles? Does he believe that God answers prayers? Does he believe the Nicene Creed? Are all these things compatible with science?

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How to Explain Creationism to People Who Don't Think Critically

 

Uncommon Descent isn't really the very best that Intelligent Design Creationism has to offer and Denyse O'Leary isn't in the same league as William Dembski and David Klinghoffer.

Nevertheless, from time to time Denyse comes up with a good example of IDiot thinking. A few days ago she asked the following question: How do you get ideas about design in nature across to people who are not learning critical thinking?.

That's easy. You write books like The Myth of Junk DNA, The Edge of Evolution, and Signature in the Cell. Non-critical-thinkers just love that sort of stuff.

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Two Kinds of Atheists

 

Let me remind you that Evolution News & Views is the Discovery Institute website. When it comes to defending Intelligent Design Creationism, this is as good as it gets.

Let me also remind you that David Klinghoffer is a Senior Fellow at the Discovery Institute. When you see an article by a Senior Fellow on the Discovery Institute website, you just know it's got to be good.

That's why I was so excited to see The Two Types of Atheists on Nov. 3, 2011.

I meant to say that broadly there are two types of people who call themselves atheists but only one really deserves the dignity of the term. The first category -- the peasant, clod, village atheist, am ha'aretz -- is the person like Jerry Coyne with a cartoon version in his head of some one religion or all religions. He rejects the cartoon, figuring that as far as faith goes in general, he's got it all figured out and it's all nonsense. This type of person typifies the New Atheist movement. He has very little of interest to say.

There's a second much rarer type, however, the person who has not only investigated at least one serious faith seriously but also experienced it, known believers, ideally was a believer himself at some adult stage of life. This person, in rejecting God, merits a real hearing.

Aren't you glad that you can get the best of the best by just reading David Klinghoffer on Evolution News & Views?

It amuses me to think of David Klinghoffer as an atheist in training.

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Professor or Hobo?

 

Can you tell the difference between a Professor and a hobo? Joseph Somody has posted a quiz. Check it out: Professor or Hobo?.

Joseph is the undergraduate winner of Monday's Molecule #147. I'll be having lunch with him on Wednesday. If you have any other pictures of professors or hobos, you could post a link in the comments and I'll be sure to pass them long. (Joseph will probably read them anyway.)

I'm thinking we could do a similar quiz for students—something along the lines of "university student or not?" There are plenty of pictures on facebook that professors could use.

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Monday's Molecule #148

 

Today, as a special treat, you get to identify three (3) different molecules. Give me the complete, unambiguous, names of these molecules to win a free lunch. Post your answer in the comments. I'll hold off releasing any comments for 24 hours. The first one with the correct answer wins. I will only post correct answers to avoid embarrassment.

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.) Every undergraduate who posts a correct answer will have their names entered in a Christmas draw. The winner gets a free autographed copy of my book! (One entry per week. If you post a correct answer every week you will have ten chances to win.)

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!)

Name the molecules shown in the figure. Remember that your names have to be unambiguous. The best way to do this is to use the full IUPAC name but usually there are traditional names that will do. In this case there are trivial names for all of the molecules but make sure you have the stereochemistry correct.

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

UPDATE: Oh, oh. There's only one correct answer—congratulations Jason Oakley. I posted another answer that's almost correct (should be L-sorbose). All the rest of you need to review your understanding of Fischer projections. Here's a hint: Name This Molecule #1.

Winners
Nov. 2009: Jason Oakley, Alex Ling
Oct. 17: Bill Chaney, Roger Fan
Oct. 24: DK
Oct. 31: Joseph C. Somody

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Advice from Jonathan Wells on Junk DNA

 

Copied from Uncommon Descent (Denyse O'Leary): What advice, on junk DNA, would Jonathan Wells give Francis Collins or Richard Dawkins?.

From the Salvo Magazine interview with Jonathan Wells, by Casey Luskin. Wells is the author of The Myth of Junk DNA:

If you could have lunch with Francis Collins and Richard Dawkins, what would you say to them about their use of the “junk DNA” argument? [that there is no design in life]

Actually, Collins no longer relies on “junk DNA.” In 2007 he announced in an interview for Wired magazine that he had “stopped using the term.” In 2010 he wrote that “discoveries of the past decade, little known to most of the public, have completely overturned much of what used to be taught in high school biology. If you thought the DNA molecule comprised thousands of genes but far more ‘junk DNA,’ think again” (The Language of Life, pp. 5–6). Unfortunately, his followers at the BioLogos Institute (which he founded) seem to be unaware of this, because they continue to promote the myth that most of our DNA is junk. I would encourage Collins to set them right.

UD News does not think Collins would succeed. They are not Collins’s followers, they are Darwin’s men. They do not seek more knowledge than Darwin had. They seek to make what he knew part of the bedrock of Christianity.

Unlike Collins, Dawkins seems utterly oblivious to recent developments in genomics. I would encourage him to read some of the scientific literature.

Why? Dawkins can command international attention for not keeping up to date – because millions of tax burdens feel he speaks for them – and they don’t need to keep up to date either. Their champions are fronts for the dead orthodoxies that keep them in place.

Dear Jonathan Wells and Denyse O'Leary,

I have read The Myth of Junk DNA and I have read the scientific literature. What advice would you give me?

Why don't you respond to my review of The Myth of Junk DNA? What are you afraid of?

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Haught vs Coyne: The Letter

As most of you know, John Haught originally tried to prevent the release of the video of their debate. You can read the history on Jerry Coyne's blog: Theologian John Haught refuses to release video of our debate.¹

You might have missed John Haught's open letter buried in the comments (#122), so here it is. You can also read Jerry's reply. Read Coyne vs. Haught - advantage, Coyne for a third party perspective on whether Coyne's behavior was appropriate.

The facts are clear, as far as I'm concerned. The sophisticated Roman Catholic theologian chose to step into the fire pit of real debate and got badly burned. Now he's whining because the fire didn't play by his rules. Maybe he thought he would be protected just like Shadrach, Meshach, and Abednego?

Seriously, we all know what this is about. It's not about whether science and religion are compatible—they aren't. It's about giving religious views special privileges that we don't give to any other viewpoints. It's about the unwritten rule that we aren't supposed to criticize someone's personal faith.

For decades that unwritten rule has given carte blanche to religious leaders who can say whatever they want about scientists and atheists knowing that they won't be challenged to defend those views. That's changing in the 21st century. John Haught seems to have just discovered that his special privileges have been revoked.

He doesn't get out very much.

An open Letter to Jerry Coyne:

Dear Jerry,

Your distorted reading of my motivation for not releasing the video of our conversation in Kentucky has given birth to an inordinate number of hostile letters to me. Because of misleading statements on your website (11/1/2011), I have received a considerable amount of hate mail, often laced with obscenities, though often also tempered with inquisitive politeness. The mail mostly complains about my “cowardly” reneging on an alleged agreement that you falsely assume I made to post online the video of our panel at the University of Kentucky. When I was in Kentucky I was never asked to do so. Later, after reflecting on what to me was a most unfortunate event, I wrote to Prof Rabel requesting that any video not be released.

Anyway, Jerry, your own words impute cowardice to me for this refusal, but how do you know that’s the reason for my reluctance? Here is a typical reaction stirred up by your remarks: “What a pathetic, sociopathic dweeb you are. Hiding behind your sick belief system you call a religion. You are an insult to academia, and a dim bulb for the uninformed masses. You deserve the insults you are getting and should be fired. Coward, liar and fool you are, loser. And no doubt a Republican too!” (I’m tempted to say that I can live with every accusation except the last.)

I want to make it clear that Rob Rabel at the University of Kentucky has confirmed that I never gave permission before or after the panel to post the video. You need to make this clear to your audience. I never broke the agreement that you have unkindly caused your readers to assume I made.

However, the more interesting issue has to do with my reasons for refusing permission to post the video, and whether it was wrong for me to do so. I have no regrets about anything I had to say during the panel, and if you agree to post this letter on your site I will be happy to have the video released unedited, for public scrutiny. Those who are reading this blog are free to look at other videos of my comments on science and religion available online. They will see that I have no need to hide my views from the public, and in fact I am quite eager to have my thoughts made available provided they are presented accurately and fairly.

Why then do I hesitate in this case? It has to do with you alone, Jerry, not anyone else, including myself. I have had wonderful conversations with many scientific skeptics over the years, but my meeting with you was exceptionally dismaying and unproductive. I mentioned to you personally already that in my view, the discussion in Kentucky seldom rose to the level of a truly academic encounter. I agree that it was probably entertaining to the audience who gave us a standing ovation at the end. Nevertheless, instead of being flattered by this I went away terribly discouraged at what had just taken place. I wish to emphasize that I do not exempt myself from criticism.

The event at the University of Kentucky did not take place in the way I had expected. My understanding was that each speaker was to provide a curt 25-minute presentation of how he understood the relationship between science and theology. I did just this, and I have no objection to having that presentation made public. People who attended the event, moreover, can testify that in my presentation I avoided talking about or criticizing you personally. Instead I was content to make some very general remarks about why I consider science completely compatible with theology as I understand it.

When Robert Rabel of the Gaines Center at the University of Kentucky, a true gentleman who remains far above reproach in all of this, contacted me last summer and invited me to participate in the event, he asked me for names of people who would differ from my own position. I recommended you as someone who would definitely have a different perspective, to say the least. Prof. Rabel informed me that you agreed to participate with the qualification that you did not want to debate me, but simply to lay out your own way of looking at science and religion. I took this to mean that you would do something parallel to what I did in my presentation.

Instead, you used the event primarily to launch a sneering and condescending ad hominem. Rather than using your 25 minutes as an opportunity to develop constructively your own belief that science and religion are always and inevitably in conflict, you were content simply to ridicule rather than refute several of my own ideas, as you interpreted them. On the other hand, my own presentation, as those who watch the video will see, was a dispassionate attempt to have the audience understand some of the reasons why the new scientific picture of the universe is so troubling to many traditionally religious people. I don’t believe that at any point in that presentation I resorted to ridicule, or that I focused on, much less misrepresented, anything you have written. Instead, I argued in a purely academic way that scientism is simply unreasonable. This was clearly my main point, and I was expecting you to respond to it in an academic manner as well.

Rather than answering my point that scientism is logically incoherent–which is really the main issue–and instead of addressing my argument that the encounter with religious truth requires personal transformation, or for that matter instead of responding to any of the other points I made, you were content to use most of your time to ridicule several isolated quotes from my books. I was absolutely astounded by your woeful lack of insight into, or willingness to grapple with, the real meaning of these passages. Sophisticated argument requires as an essential condition that you have the good manners to understand before you criticize. Your approach, on the other hand was simply one of “caricature and then crush.” Citation of a few isolated sentences or paragraphs, the meaning of which requires reading and understanding many chapters, is hardly useful criticism. You grossly distorted every quotation you used, and then you coated over your [mis]understanding of these statements with your own uncritical creationist and literalist set of assumptions about the Bible and theology. There was no room for real conversation, as impartial viewers will notice.

Instead of trying to convince the audience of the logical coherence and philosophical finality of your belief that science is the only reliable guide to truth, you began by arbitrarily announcing to the audience that John Haught is the chief representative of theology in the conversation of science with religion. You gave no evidence for that, and in fact it is by no means evidently true. I am but one of a great number of theologians involved in the discussion, and many others do not share my views. But your strategy was to show that if the principal figure is stupid, then you need not take his subordinates seriously either. This is a convenient method for shrinking the territory that needs to be covered, but it is hardly a fair way of dealing with all the other theological alternatives to your own belief system.

But let me come to the main reason why I have been reluctant to give permission to release the video. It is not for anything that I said during our encounter, but for a reason that I have never witnessed in public academic discussion before.

I’m still in shock at how your presentation ended up. I was so offended both personally and as an academic by the vulgarity of it all that I did not want other people to have to share what I witnessed that night in October. I still don’t.

I’m referring to the fact that your whole presentation ended up with a monstrous, not to mention tasteless, non sequitur, to give it the kindest possible characterization. You put on the screen a list of all the “evils” you associate with Catholicism: its stance regarding divorce, contraception, priest pedophilia, homosexuality–and I can’t remember what all–as though these have anything at all to do with the topic of the panel or with my own personal views on the relationship of science to theology. The whole focus of your presentation was on me, but when you came to your conclusion you never bothered to find out what my own position regarding your list of Catholic evils might be. I have never witnessed such a blatant smear or malicious attempt to impute guilt by association in all my years in university life.

Your list of Catholic evils, contrary to what you were suggesting, has absolutely nothing logically to contribute to your argument that science is opposed to religion. But even if it did, you never asked me whether I dissent from some or all the items on your list of “evils,” as many Catholics do, and whether such dissent might, in your twisted way of arguing, perhaps make my own position more credible. Your insinuation could only have been that somehow the priest sexual abuse crisis, for example, discredits my views on science and theology. You should be grateful that I have tried to protect the public from such a preposterous and logic-offending way of bringing your presentation to a close.

There is much more to be said, but this is all I will have to say to you or others on this matter. If you are willing to post this letter on your blog, go ahead and ask the Gaines Center to release the video as well. I have no objections now that I have had the opportunity to present my reservations to possible viewers.

Sincerely,

John Haught

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1. I'm looking for articles from anyone who thinks that Haught did a good job of making the case for compatibility. Post a link in the comments.

Haught vs Coyne: "Science and Religion: Are They Compatible?"

John Haught and Jerry Coyne "debated" the topic of compatibility at the University of Kentucky on October 12, 2011. If you are interested in this topic you MUST watch the entire video AND the question and answer session.¹

This is a classic confrontation between a "sophisticated" theologian and a scientist who knows what religion really is (in South Chicago).

The sophisticated theologian is John Haught, a Roman Catholic (with all that implies). His talk consisted largely of the claim that there are many different layers of explanation. According to Haught, science, by definition, can only address one layer—the naturalistic layer. He claims that he and his fellow theologians are "explanatory pluralists" whereas atheist scientists are "explanatory monists."

By implication, it's better to be an explanatory pluralist IF THE MULTIPLE LAYERS OF EXPLANATION ACTUALLY EXIST. Haught offers not one iota of evidence for the existence of those multiple layers beyond a childish story about boiling water to make tea. (It's the same story he used in the Kizmiller v. Dover trail.)

Haught does not address alternative definitions of science even though a bit of homework would have shown him that Jerry Coyne doesn't accept his definition of science. Apparently, Haught didn't do his homework. This is surprising since Haught's entire case depends on accepting the idea that science and religion are compatible because science can't address the supernatural. In other words, compatibility by fiat.

You'd think that a "sophisticated" theologian would be prepared for someone who challenges that definition. Haught wasn't prepared. In fact, even during the Q&A he doesn't seem to have grasped the problem.

Haught conveniently "forgets" to mention anything about his religious beliefs other than that they involve personal revelation (faith). He doesn't tell us what he believes about transubstantiation, miracles, the virgin birth, the efficacy of prayer, the resurrection, the existence of a soul, heaven, hell, angels etc. That's a shame because Jerry Coyne addresses most of those beliefs and argues that they are incompatible with science. Haught will only reveal (in the Q&A) that he doesn't believe in any of the things Coyne addressed in his presentation. One wonders if Haught is really a Roman Catholic.

I'm getting pretty disgusted with those "sophisticated" theologians who hide behind fuzzy notions of religion when you know damn well they believe in a personal god who intervenes in the world. Haught has been playing this game for decades. Either he's a deist—in which case he should come right out and admit it—or he believes in a personal god who does things that possibly conflict with science—in which case he should have the courage to defend his beliefs.

2011 Bale Boone Symposium - Science & Religion: Are They Compatible? from UK Gaines Center on Vimeo.

Science and Religion: Are They Compatible? October 12, 2011 Q+A with Jerry Coyne and John Haught from UK College of Arts & Sciences on Vimeo.

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1. There's a special treat in store for those who watch the Q&A. You will get to see an incredibly stupid first question from the moderator. I don't think I could have restrained myself the way Jerry Coyne did.

John Haught in Kitzmiller v Dover

John Haught has been in the blogosphere news recently because of his debate with Jerry Coyne. The discussion of that now-famous video is going to last for a few more days and many different issues will be brought up. One of them will be accommodationism and whether John Haught should be treated as one of the "good guys" or one or the "bad guys." I've heard prominent accomodationists complain about Coyne's "attack" on Haught on the grounds that we shouldn't be criticizing a prominent theologian who is allied with evolutionary biologists in the fight against creationism.

Haught testified for the Kitzmiller side in Kiztmiller v Dover (2005). Here's part of his testimony when being questioned by the attorney for the parents (Mr. Wilcox). [transcript: Haught testimony]

Q. Focusing on natural science, what is science?

A. Science is a mode of inquiry that looks to understand natural phenomena by looking for their natural causes, efficient and material causes. It does this by first gathering data observationally or empirically. Then it organizes this data into the form of hypotheses or theories. And then, thirdly, it continually tests the authenticity of these hypotheses and theories against new data that might come in and perhaps occasionally bring about the revision of the hypothesis or theory.

The American Justice System Is Based on the Ten Commandments

 
Bill O'Reilly is the highly paid host of a prime time TV show on one of the most popular networks in the United States. I was recently watching this video and one of O'Reilly's statements caught my attention.



About two minutes into the segment, O'Reilly says ...

Alternative Splicing and Why IDiots Don't Understand How Science Works

One of the characteristics of creationists is their inability to understand how science works. For example, in biology, our knowledge of how living things work advances in fits and starts with many hypotheses being tested and rejected before we arrive at a consensus.

At any given point in time there are a number of "works in progress" where scientists have not settled on a definitive model. Many papers will be published and a good number of them will turn out to be wrong. Creationists exploit genuine scientific controversies in two ways: (1) they use them to discredit science, and (2) they selectively quote from those on one side of an issue without mentioning that many other scientists disagree. (Most creationists use both tactics, sometimes in the same paragraph.)

We saw how Jonathan Wells did this in The Myth of Junk DNA. He picked papers that question junk DNA and used them to try and show that the issue has not been settled in spite of what some leading scientists say. This is a valid point, but he goes on to conclude that junk DNA is a myth when the proper conclusion is that scientists haven't reached a consensus but the majority favor junk DNA.

He also selected specific papers that showed evidence of function for some part of the genome without mentioning that this evidence is often disputed. In many cases it isn't clear whether this "evidence" is correct. He ignores controversy when it suits him and exploits it when it's to his benefit.

Some papers have claimed that most of the human genome is transcribed. Wells takes this as evidence that the transcribed DNA is not junk. In this particular case, the objections to this interpretation couldn't be ignored so he spends a page or so dismissing the idea that the data might be wrong and that the conclusion might be wrong. He forgets to mention that the consensus among molecular biologists is that most of the transcript are junk RNA due to accidental transcription. The DNA being transcribed is still junk.

Jonathan M makes a similar mistake in his latest posting [Why the "Onion Test" Fails as an Argument for "Junk DNA"]. The issue is alternative splicing. There are many scientists who think that alternative splicing is widespread in the human genome. Some claim that the vast majority of human genes (>90%) make two or more biologically functional alternative transcripts. This is usually offered as one "explanation" for why humans don't have as many genes as our egos demand [The Deflated Ego Problem]. Fact is, most of us never thought this was a problem in the first place so no "solution" is required.

Here's how Jonathan M describes alternative splicing ....

Alternative Splicing and Genome Size

A second point I made was that the phenomena of alternative splicing and alternative polyadenylation may have some explanatory power when it comes to accounting for the C-value enigma. Alternative splicing allows a single form of a pre-mRNA transcript to be spliced into a number of different forms by skipping exons or by recognizing alternative splice sites. I stated that the level of alternative splicing exhibited in humans (more than 90%, with an average of 2 or 3 transcripts per gene) is much higher than that for C. elegans (about 22%, with less than 2 transcripts per gene), and argued that this may, in part, explain why humans have only marginally more genes than C. elegans, which is otherwise seemingly paradoxical given the complexity of humans as compared to the roundworm.

I don't really understand the connection between alternative splicing and the C-value paradox. How does it explain why closely related species of onion have very different genome sizes?

But that's not the point I want to make. When Jonathan M raised this issue before, I replied, "I don't agree with the facts. I don't think it's true that most human genes produce multiple functional copies of mRNA by alternative splicing."

That prompted the following response ...

On this point, Moran is not just in disagreement with me, he is also out-of-date with the literature by about ten years! As this 2008 article from Science Daily reports,

Nearly all human genes, about 94 percent, generate more than one form of their protein products, the team reports in the Nov. 2 online edition of Nature. Scientists' previous estimates ranged from a few percent 10 years ago to 50-plus percent more recently.

"A decade ago, alternative splicing of a gene was considered unusual, exotic ... but it turns out that's not true at all -- it's a nearly universal feature of human genes," said Christopher Burge, senior author of the paper and the Whitehead Career Development Associate Professor of Biology and Biological Engineering at MIT.

Wang et al. (2008), moreover, report in Nature,

Through alternative processing of pre-messenger RNAs, individual mammalian genes often produce multiple mRNA and protein isoforms that may have related, distinct or even opposing functions. Here we report an in-depth analysis of 15 diverse human tissue and cell line transcriptomes on the basis of deep sequencing of complementary DNA fragments, yielding a digital inventory of gene and mRNA isoform expression. Analyses in which sequence reads are mapped to exon-exon junctions indicated that 92-94% of human genes undergo alternative splicing, ~86% with a minor isoform frequency of 15% or more.

I've written about IDiots and alternative splicing before, especially their inability to understand what they're talking about [Jonathan Wells Weighs in on Alternative Splicing]. But the issue here is somewhat different. It's whether the idea that most human genes are alternatively spliced is a scientific fact or whether it's controversial. Like most IDiots, Jonathan M doesn't understand the subject well enough to know the difference.

Just because there are some papers making truly outlandish claims about alternative splicing doesn't mean they are correct—no matter where those papers are published. In order to understand science you have to dig deeper than that and decide whether the claims have been accepted.

The claim of abundant alternative splicing (i.e. the vast majority of human genes have two or more functional transcripts) has not been accepted. It's a scientific controversy. Hardly any molecular biologist believes that >90% of our genes produce functional alternative transcripts in spite what Jonathan M might believe.

In some cases it's a matter of definition. My colleague, Ben Blencowe, for example, has played a prominent role in promoting the idea that >90% of human genes are alternatively spliced (Pan et al, 2008) but he tells me that this does not mean that all alternative transcripts are functional. He concedes that many of the these transcripts could be due to splicing errors but they still qualify as alternative splicing events.

I don't agree with that definition. Many of us began teaching alternative splicing back in 1980 and putting in textbooks a few years later. "Alternative splicing" always meant "functional" alternatives. It means that the gene produced more that one biologically functional product. The definition changed in the past decade or so, but most people still interpret abundant alternative splicing to mean abundant functional products.

No reasonable molecular biologist could look at the database of spliced transcripts and conclude that most of them have a biological function. (See Two Examples of "Alternative Splicing" to see if you agree.) Most of those transcripts are clearly due to splicing errors just as most of the minor genome transcripts are due to transcription errors. There's just as much junk splicing as there is junk RNA.

Anyone familiar with the subject of alternative transcription knows that the conclusions are controversial. They know that many scientists are skeptical of the claims for massive amounts of functional alternative splicing. They know that those extraordinary claims don't make sense in the light of evolution and are probably wrong. (See A Challenge to Fans of Alternative Splicing.)

Here are some papers from well-known labs attempting to deal with the controversy.

Zhang et al. (2009)

Nonsense-mediated decay is a mechanism that degrades mRNAs with a premature termination codon. That some exons have premature termination codons at fixation is paradoxical: why make a transcript if it is only to be destroyed? One model supposes that splicing is inherently noisy and spurious transcripts are common. The evolution of a premature termination codon in a regularly made unwanted transcript can be a means to prevent costly translation. Alternatively, nonsense-mediated decay can be regulated under certain conditions so the presence of a premature termination codon can be a means to up-regulate transcripts needed when nonsense-mediated decay is suppressed....

We conclude that for recently evolved exons the noisy splicing model is the better explanation of their properties, while for ancient exons the nonsense-mediated decay regulated gene expression is a viable explanation.

Tress et al. (2007)

Alternative premessenger RNA splicing enables genes to generate more than one gene product. Splicing events that occur within protein coding regions have the potential to alter the biological function of the expressed protein and even to create new protein functions. Alternative splicing has been suggested as one explanation for the discrepancy between the number of human genes and functional complexity. Here, we carry out a detailed study of the alternatively spliced gene products annotated in the ENCODE pilot project. We find that alternative splicing in human genes is more frequent than has commonly been suggested, and we demonstrate that many of the potential alternative gene products will have markedly different structure and function from their constitutively spliced counterparts. For the vast majority of these alternative isoforms, little evidence exists to suggest they have a role as functional proteins, and it seems unlikely that the spectrum of conventional enzymatic or structural functions can be substantially extended through alternative splicing.

Melamud and Moult (2009)

The number of known alternative human isoforms has been increasing steadily with the amount of available transcription data. To date, over 100 000 isoforms have been detected in EST libraries, and at least 75% of human genes have at least one alternative isoform. In this paper, we propose that most alternative splicing events are the result of noise in the splicing process. We show that the number of isoforms and their abundance can be predicted by a simple stochastic noise model that takes into account two factors: the number of introns in a gene and the expression level of a gene. The results strongly support the hypothesis that most alternative splicing is a consequence of stochastic noise in the splicing machinery, and has no functional significance. The results are also consistent with error rates tuned to ensure that an adequate level of functional product is produced and to reduce the toxic effect of accumulation of misfolding proteins. Based on simulation of sampling of virtual cDNA libraries, we estimate that error rates range from 1 to 10% depending on the number of introns and the expression level of a gene.

This is a controversial topic. Some of us believe that alternative splicing in human genes is not particularly widespread and most of the data can be explained as errors in splicing. Others believe that the data is real and most human genes produce multiple transcripts with different biological functions.

It doesn't matter so much which side you pick. What matters is that you understand science well enough to know that the data and the conclusions are disputed. What this means is that you cannot just assume that >90% of human genes are alternatively spliced and use this "fact" to bolster your case for Intelligent Design Creationism.

I'm tempted to say that Jonathan M is "... out-of-date with the literature by about ten years!" but that would be unkind.

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Melamud, E. and Moult, J. (2009) Stochastic noise in splicing machinery. Nucleic Acids Res. 37:4873-4886. [doi: 10.1093/nar/gkp471]

Pan, Q., Shai, O., Lee, L.J., Frey, B.J., and Blencowe, B.J. (2008) Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing. Nat Genet. 2008 Dec;40(12):1413-5. Epub 2008 Nov 2. [doi:10.1038/ng.259]

Tress, M.L., Martelli, P.L., Frankish, A., Reeves, G.A., Wesselink, J.J,, Yeats, C., Olason, P.I., Albrecht, M., Hegyi, H., Giorgetti, A., Raimondo, D., Lagarde, J., Laskowski, R.A., López, G., Sadowski, M.I., Watsonk J.D., Fariselli, P., Rossi, I., Nagy, A., Kai, W., Størling, Z., Orsini, M., Assenov, Y., Blankenburg, H., Huthmacher, C., Ramírez, F., Schlicker, A., Denoeud, F., Jones, P., Kerrien, S., Orchard, S., Antonarakis, S.E., Reymond, A., Birney, E., Brunak, S., Casadio, R., Guigo, R., Harrow, J., Hermjakob, H., Jones, D.T., Lengauer, T., Orengo, C.A., Patthy, L., Thornton, J.M., Tramontano, A., and Valencia, A. (2007) The implications of alternative splicing in the ENCODE protein complement. Proc. Natl. Acad. Sci. USA 104:5495-5500. [doi: 10.1073/pnas.0700800104]

Zhang, Z., Xin, D., Wang, P., Zhou, L., Hu, L., Kong, X., and Hurst, L.D. (2009) Noisy splicing, more than expression regulation, explains why some exons are subject to nonsense-mediated mRNA decay. BMC Biol. 7:23-36. [doi:10.1186/1741-7007-7-23]

Jonathan M Flunks the Onion Test, Again

 

A few weeks ago I explained why Jonathan M is an IDiot [A Twofer]. The topic was junk DNA. Jonathan M had posted an article on Uncommon Descent where he claimed that The Onion Test is an argument in favor of junk DNA [Thoughts on the “C-Value Enigma”, the “Onion Test” and “Junk DNA”].

I explained, as politely as I could (not), that the onion test was not an argument in support of junk DNA. It's a "test" for those who think they can explain the presence of large amounts of supposedly functional DNA that looks a lot like junk. The "test" is to apply your reasoning to the genomes of various onion species to see if it makes sense.

Do you think that the excess DNA protects against mutations? Then why do some onions need a lot more protection than humans?

Do you think that the extra DNA can be explained by alternative splicing? Why do some onion species need more alternative splicing than others?

Do you think that most of the extra DNA is required for regulating gene expression? Then why do onions need more sophisticated regulation than humans?

This ain't rocket science. The description of the Onion Test is pretty easy to understand—unless, of course, you are an IDiot.

Jonathan M has taken another shot at attacking the Onion Test. This time his article appears on the official blog of The Discovery Institure: Why the "Onion Test" Fails as an Argument for "Junk DNA". The title sort of gives it away, doesn't it? We're still dealing with an IDiot.

Briefly stated, the often cited "onion test" observes that onion cells have many times more DNA than human cells do. And since the onion is considered to be relatively simple as compared to us, this discrepancy -- it is argued -- can only be accounted for if the preponderance of its DNA is, in fact, junk or non-functional. Let's see whether the concept really holds any water.

Let's go over this one more time. The Onion Test is a "test." (Look up the word "test" in the dictionary.) It's designed as a thought experiment to test a hypothesis about the possible function of large amounts of noncoding DNA. If you think you have an explanation for why most of the human genome has a function then you should explain how that accounts for the genomes of onions. Ryan Gregory knew that most so-called explanations look very silly when you try using them to account for genome size in onion species.

The Onion Test is not an argument in favor of junk DNA. It's a reality check on speculations about function.

Jonathan M still doesn't get it.

Are we surprised?

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Carnival of Evolution #41

 
This month's Carnival of Evolution (41st version) is hosted by Anne Buchanan, from the Anthropology Department at Pennsylvania State University (USA). She blogs with her friends at the mermaid's tale: The Carnival of Evolution #41.

Each month, a fascinating hodge-podge of evolution-themed posts from blogs both big and small is collected in a single place and heralded far and wide. Or as far and wide as interested bloggers can herald it. Evolution is a broad topic with broad areas of agreement, some controversy (within the science itself), and regular surprises. So, if you're interested in evolutionary issues, post, tweet, text, or even speak the 41st CoE!

The next Carnival of Evolution will be hosted by Psi Wavefunction at The Ocelloid. You can submit your articles for next month's carnival at Carnival of Evolution. Here's the website: Carnival of Evolution.

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Better Biochemistry: The Free Energy of ATP Hydrolysis

This is part of a series on important concepts in biochemistry. I'm concentrating on those concepts that may be widely misunderstood and/or not well described in most textbooks. Naturally, I think we do a pretty good job in our book!

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We usually think of ATP as a "high energy" molecule because the hydrolysis of ATP to ADP or AMP releases a lot of energy.¹ The standard Gibbs free energy change for the two reactions shown in the large figure aren't terribly relevant because, for simplicity, I've left out a key component of the reaction.

Mg²⁺ ions are an essential part of the reaction in vivo. They are bound to adjacent phosphate groups as shown below and this ATP:Mg²⁺ complex has different thermodynamic properties than free ATP.

In addition, the standard Gibbs free energy changes aren't very useful when you're dealing with charged molecules and the ATP hydrolysis reactions have charged molecules—even when some of the negative charges are neutralized by Mg²⁺ ions. That's why it's better to calculate new values of "standard" Gibbs free energy changes in the presence of Mg²⁺ ions and an ionic strength that's closer to physiological values.

Recall that the traditional standard Gibbs free energy changes are at 25°C (298 K) and pH 7.0. For reactions like ATP hydrolysis, we want a new "standard" that includes 3mM Mg²⁺ and ionic strength = 0.25 M.

Robert Alberty and his colleagues have calculated the transformed free energies of hydrolysis for many biochemical compounds (Alberty and Goldberg 1992) and those are the values we should use in biochemistry courses.

The table (below right) shows the standard Gibbs free energy changes for the ATP reactions in the presence of 3 mM²⁺ and ionic strength = 0.25 M. Note that the values are large and negative. That means a lot of energy is given off. This energy can be captured and used in enzyme catalyzed reactions.

If you've been paying attention to the previous postings in this series—as I'm sure you have—you'll remember that standard Gibbs free energy changes don't mean very much in biochemistry. What really counts is the actual free energy change and that depends on the in vivo concentrations of reactants and products.

You'll also remember that most biochemical reactions reach equilibrium (near-equilibrium reactions). At equilibrium concentrations ....

ΔG_reaction = 0 kJ mol^-1.

ATP would be completely useless as a "high-energy" compound if the hydrolysis reaction was a near-equilibrium reaction. That's why these reactions can never be allowed to reach equilibrium. Cells would die if this ever happened.

Most of the reactions that use up ATP are regulated. What this means is that the activity of the enzyme is inhibited if the concentration of ATP falls too much, relative to ADP (or AMP). If the concentration of ATP is always high relative to the products then there's still a large negative ΔG for the reaction and this energy can be used to drive other reactions.

So, we know that the actual Gibbs free energy isn't the same as the standard Gibbs free energy but what is it's actual value? The short answer is that in most cases we don't know. It has to be some large negative value but it's very difficult to measure the concentrations of ATP, ADP, AMP, and inorganic phosphate inside cells.

The situation isn't entirely hopeless since there are some good estimates. Unfortunately the best examples come from rat hepatocytes and erythrocytes¹. We don't know if this is typical of all cells (bacteria, plants etc.) or whether mammalian cells are special.

We can calculate the actual Gibbs free energy change for ATP hydrolysis (to ADP) given the known concentrations of reactants and products in rat hepatocytes. The answer is ΔG = -48 kJ mol^-1. Thus, the actual Gibbs free energy change is 1½ times the standard Gibbs free energy change. This has important consequences when we try to figure out how ATP is synthesized and where that energy comes from.

There's an easy way to tell the difference between a good introductory biochemistry textbook and the other kind. Check out the standard Gibbs free energy change for the ATP → AMP + PP_i reaction. If the value is close to -45 kJ mol^-1 then it's probably a good textbook. If the book also mentions that the actual Gibbs free energy of the ATP → ADP + P_i reaction is close to -50 kJ mol^-1 then it's almost certain to be a good textbook.

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1. I put "high energy" in quotation marks because it's really the Gibbs free energy of the reaction (system) that we're referring to and not an individual molecule.

2. Rat liver biochemistry used to be very popular.

Alberty, R.A. and Goldberg, R.N. (1992) Standard thermodynamic formation properties of adenosie 5′-triphosphate series. Biochem. 31:10610-10615.

Monday's Molecule #147

 

Give me the complete, unambiguous, name of this molecule to win a free lunch. Post your answer in the comments. I'll hold off releasing any comments for 24 hours. The first one with the correct answer wins. I will only post correct answers to avoid embarrassment.

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.) Every undergraduate who posts a correct answer will have their names entered in a Christmas draw. The winner gets a free autographed copy of my book! (One entry per week. If you post a correct answer every week you will have ten chances to win.)

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!)

Name the molecule shown in the figure. Remember that your name has to be unambiguous. The best way to do this is to use the full IUPAC name but usually there are traditional names that will do.

Winners
Nov. 2009: Jason Oakley, Alex Ling
Oct. 17: Bill Chaney, Roger Fan
Oct. 24: Bill Chaney

UPDATE: The winner is Joseph C. Somody.

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