Sternberg Plasters Matheson

_{Salvador Cordova

June 13, 2010

Biology, Darwinism, Science}

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“I think this will come to be a classic story of orthodoxy derailing objective analysis of the facts, in this case for a quarter of a century…The failure to recognize the full implications of this-particularly the possibility that the intervening noncoding sequences may be transmitting parallel information in the form of RNA molecules-may well go down as one of the biggest mistakes in the history of molecular biology.”

—John Mattick, Molecular biologist, University of Queensland, quoted in Scientific American

Steve Matheson, a teacher and Darwinist promoter at a religious school, repeats the biggest mistake in molecular biology. In contrast, Richard Sternberg, an evolutionary biologist at the Biologic Institute, defends objective analysis of the facts. See Sternberg’s defense of the facts against Matheson’s Darwinist ideology in the essay: Mathesons Intron Fairytale.

Comments

Can I pin you down on the specifics of that? What’s the (your) ID prediction for introns in general? That they all have function? 50% have function? 1% has function? That most or 50% plus will be found to have function.tribune7_{June 20, 2010
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tribune7
If one party predicts a thing will happen — say a function will never be found for a particular intron — and the other party predicts the opposite and it should come to pass, the party making the successful prediction will gain credibility at the expense of the other.
Can I pin you down on the specifics of that? What’s the (your) ID prediction for introns in general? That they all have function? 50% have function? 1% has function?Ena Sharples_{June 20, 2010
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BP engineers who issued warnings about the practices in place but with the corporate management and political regulators (yes this means Obama) who made decisions apparently based on hubris and greed. . . .So it’s Obama’s fault? What an ironic way of phrasing it :-) Yes, it is partly Obama's fault That does not, btw, exempt the corporate leaders who appeared to have ignored the warnings from their engineers whom my initial post was defending. Even if Neo-Darwinism were to be falsified in such a manner how does that support ID? If one party predicts a thing will happen -- say a function will never be found for a particular intron -- and the other party predicts the opposite and it should come to pass, the party making the successful prediction will gain credibility at the expense of the other. You are correct, though, in that falsifying Neo-Darwinism does not prove ID.tribune7_{June 20, 2010
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tribune7
The Deepwater Horizon disaster wasn’t the fault of BP engineers who issued warnings about the practices in place but with the corporate management and political regulators (yes this means Obama) who made decisions apparently based on hubris and greed.
So it's Obama's fault? What specific decision did Obama make before this event that can be said to have caused it?
Something for Neo-Darwinists to consider : Will Neo-Darwinists agree that Neo-Darwinism has been falsified if functions are found for the introns not now known to have functions?
Even if Neo-Darwinism were to be falsified in such a manner how does that support ID? Disproving A does not support B! What's the ID prediction for introns? That they all have function? 50% have function? 1% has function? What? That prediction is not clear to me from reading this entire thread.Ena Sharples_{June 20, 2010
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Unfortunately for you, the human genome wasn’t designed by an engineer, unless it was the same one who works for BP. The problem with bon mots in technical debates is that they usually only reveal ignorance. The Deepwater Horizon disaster wasn't the fault of BP engineers who issued warnings about the practices in place but with the corporate management and political regulators (yes this means Obama) who made decisions apparently based on hubris and greed. What's illustrative of the "human genome wasn't designed by an engineer" dig is that it is designed to dismiss not enlighten and very well be motived by the same reasons that caused the BP disaster. Something for Neo-Darwinists to consider : Will Neo-Darwinists agree that Neo-Darwinism has been falsified if functions are found for the introns not now known to have functions?tribune7_{June 20, 2010
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scordova, In the case of your example the function is not sight, but the appropriate suppression of sight. I think that would qualify as function if you found it in an intron. Clumsy? No need to be perjorative. Megabase knockouts are simply working on larger chunks of the genome to target the important areas for more detailed study later. Looking again at the reports on the megabase deletion experiments that have been done, it seems that the scientist are aware of, and sensitive to, your concerns. I'm sure if the DI conducted similar experiments, they would also be sensitive to them. The overall point from the perspective of our discussion is that it is a very powerful form of argument (to prove your point) to assume the negative and then reason to a contradiction. Doing megabase knockouts would be a fast way of doing that. BTW, here is an article I came across on function in gene deserts that is generally supportive of the idea of function in non-coding DNA. It may also provide some clues, methods, or possible collaborators for DI-funded experiments on this topic.Nakashima_{June 18, 2010
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The ultimate context in which function should be judged is competition against wild type mice in a wild environment.
Not necessarily. Consider blind cave fish. Their blindness is hypothesized by many (including myself) to confer advantage since it has lower metabolic load on fish in dark underwater caves (where seeing isn't any benefit anyway). In such an environment, blindness confers advantage over seeing. Using the competition benchmark in the wild, do we then say the ability to see is junk? No! The way to elucidate function is not by selective advantage. Andreas Wagner and Lewontin have put forward arguments as to why, especially since fitness is difficult to universally define. Function is better elucidated via comparing architectures and pattern recognition. If an engineer is trying to understand how something works (like say a bridge or space ship), knocking parts out might be one way to make a detection, but it's kind of clumsy! One technique to detect function is to take a given cell type and try to find ways to stimulate an alternative splice. This is not to different from techniques used in reverse engineering and it is less clumsier than knockout! An experimental example? Hmm: Corticotropin-releasing hormone triggers differentiation in HaCaT keratinocytes I'd say knockout should be a bit of a last resort, and should be done with the caveats I stated in mind.scordova_{June 17, 2010
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That is simply not true, and is not supported by anything written in the paper.anaruiz_{June 17, 2010
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The only reason they looked at only 300nt (and not more) is because the more sequence you look at, the less likely you are to find bona fide features, because you lose statistical precision.
No, the reason for the 300 nt focus is because this is where the known intronic splicing enhancers/silencers lie. This region was determined by decades of biochemistry.Arthur Hunt_{June 17, 2010
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all of the intronic cis-elements involved in AS take up all of 600 nts (or less) of your generic AS intron. If each and every intron has 600 nts of such cis elements, that adds up to less than 2% of all intronic sequence.
The only reason they looked at only 300nt (and not more) is because the more sequence you look at, the less likely you are to find bona fide features, because you lose statistical precision.anaruiz_{June 17, 2010
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scordova, You've asked me to shift my discussion of introns to this thread, from your other Matheson thread. In your response there, you mention your airplane magneto example. I'm sure that if some set of introns is functional but redundant, knockouts would eventually reveal that fact. We know that magneto A is redundant with magneto B, not door handle F. Experiment would similarly reveal these details redundant function if they exist. You also raise the issue of function in context. I agree it is possible for knockouts to eliminate function that is not immediately obvious. The ultimate context in which function should be judged is competition against wild type mice in a wild environment. Again, this is a matter for the experimental design to include, not a reason to avoid doing the experiment. Knockout experiments have been very helpful in finding which specific sequences have which specific functions. If introns have function, knockouts can help elucidate that function. You have a testable prediction, why not use the tool?Nakashima_{June 17, 2010
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Arthur Hunt (#92): (continuation: the previous posy gor posted almost by itself while I was writing it :) ) So, as I was saying, as far as I can see form your own words, Meyer himself was not in principle unreceptive to your suggestions, and that's a sing of open mind and humbleness, which are the greatest virtues in scientific debate. Anyway, it's not my duty to defend Meyer. I suppose he can do that himself perfectly well. So, let's go to the second point, which is certainly more important. 2) While I perfectly agree with you about the supreme importance of all degradation mechanisms in biological regulation (there are lots of examples, including obviously those you cited, which are of utmost relevance), I must say that I don't understand the concepts which you seem to derive from that fact. You say: So, again, the leading light of the ID movement was totally unaware of a crucial process, one that involves degradation, turnover, and “garbage”. and: So, on top of years of making similar points on the ARN and ISCID boards, (and here, when Dave Scot told me that this approach to regulation made no sense), this most recent experience reinforces my claim. I think it’s valid, and it reflects the disconnect between the ways cells really work and the ways that “design principles” might work. First of all, just as a humourous note, I would mention that you were not the only one who had some problem with DaveScot: many of us, including me, share that experience :) With this, I don't want in any way to criticize him, or diminish his contribution to this blog, but just state a well known fact. But let's go to the substantial point. Leaving apart the reference to Meyer, I believe what you are saying is: the way cells work is different form the way machines work; so, while machines obey to design principles, cells don't (more or less, I just want to make the point more explicit here, it's not my intention to put words in your mouth...) If that is your point, then I don't agree. There is no doubt that cells work in a different way, let's say, than an automobile or a computer. They are different kinds of machines, but still machines they are. And still designed they are. Obviously, the implementation of design is different in different kinds of machines: The design of a mechanical engine is not the same as the design of a software program, or of a radio transmitter. Each situation needs specific approaches, The same nature of the chosen hardware material poses rules and constraints to the design. But why do you think that such a difference implies a difference in the "principles" of design? The only universal principle of design is that the designer, a consciuous intelligent being, is responsible for searching and finding some ordered structure which can accomplish a specific function. That process, well known to programmers, is called implementation, and it is universally valid for all designed things, however big the differences in the implementation procedures may be. Moreover, It's not true that the importance of degradation and turnover of functional units (I still don't see why you use the term "garbage") is unique to biological machines. Whoever has some acquaintance with programming, knows well that, especially in object oriented programming, the building, span of life, visibility and degradation os softwrae objects is one of the leading principles for the programmer. Objects are continuosly built and destroyed in software programs, so that they may perform their function and then release the necessary resources. Errors in these finely regulated networks can really affect the working of the program. So, again, where is the difference? IMO, the finely regulated network of synthesis, modifications and degradation which we can see in all biological networks, but especially in protein networks and in the extremely complex and crucial nuclear network of transcription factors and regulatory RNA elements, which we are just beginning to understand, are and will increasingly become the best evidence of design in the cell.gpuccio_{June 17, 2010
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Arthur Hunt (#92): First of all, I want to thank you for your intellectually honest and deeply competent contribution to this debate. That is really from the heart, there is nothing I appreciate more than good interlocutors, especially those which have different ideas. That said, I must say that I agree with your last post completely on the scientific points, with some distinctions on a couple of points: 1) I find nothing strange if Meyer was not specially sensitive to the points you raised. ID is a work in progress, nobody knows all, and nobody represents ID on a plane of authority. As all scientific paradigms, ID is of all and for all. People like Behe, Dembski and Meyer, IMO, deserve a very deep repsect and admiration for the work they are doing, and have contributed immensely to the cause of ID, but nobody of them is a dogma or an absolute authority. One of the problems in ID is the paucity of biologists in the group (which can easily be explained in many ways, not necessarily those that darwinist would like to argue :) ). That's why the contribution of serious darwinist biologists to the ID debate can really be precious. As fargpuccio_{June 16, 2010
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Art, Certainly it is appreciated that you are contributing here, not withstanding your self-serving and unnecessary personal attacks against Meyer. I haven't had the opportunity to listen through the audio of the debate, yet I wonder. Perhaps what you perceived at being perplexed in Meyer, was a misread on your part. Perhaps it was more aligned with him being underwhelmed - if not dismayed. The role of degradation as a mechanism in regulation does absolutely nothing to the core of his argument - which is (I am certain) what he was there to defend. If you want to make the argument that the source of functional complexity/information can be found within the question of junk DNA, then just make it.Upright BiPed_{June 16, 2010
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gpuccio @ #47: Sorry for losing this in the flurry. You said, when I mentioned how the "garbage disposal" isn't on the radar screens of IDists:
I don’t agree with you. Why do you think that IDists are not aware that intronic RNA is made and then discarded? First of all, practically everything in the cell is “made and discarded”. Cells are typically “far from equilibrium” systems. Some structures are more stable, others more transient. But that’s no reason to infer that the transient ones are less functional. On the contrary, they could be transient exactly because that is connected to their function.
Yes! (To everything but the first sentence.) But the fact of the matter is that IDists either don't appreciate or are opposed to these concepts. As an example to support my case, allow me to summarize my experience at Biola on May 14. I approached this as a chance to grill the leader of the ID movement, the person who has written the defining book on the subject, one who states often in the book that his research, as it were, makes him well-appointed to pass judgment on the science of design and anti-Darwinism. I only got to ask a few questions, but two of them touched on the theme of the "garbage disposal". I asked Meyer about polyadenylation,and included in a listing of its importance the fact that it is important for RNA degradation (in bacteria, and for the degradation of the numerous nuclear junk RNAs that Sternberg is vainly trying assign function). Meyer actually did not seem to even know what polyadenylation is (I had to repeat the term, and I feared I would have to spell it out), and he declined to challenge my assertion that junk RNA really is junk. In other words, the crucial role that RNA degradation plays in regulation and quality control was just not on his radar screen. Neither was the entire field of E3 ubiquitin ligase-mediated degradation of proteins, and the central importance of the process in biology. When I mentioned this subject, he seemed totally perplexed. And he actually agreed with my argument, made using this example, that the analogy between machines and living cells was not a good one. So, again, the leading light of the ID movement was totally unaware of a crucial process, one that involves degradation, turnover, and "garbage". So, on top of years of making similar points on the ARN and ISCID boards, (and here, when Dave Scot told me that this approach to regulation made no sense), this most recent experience reinforces my claim. I think it's valid, and it reflects the disconnect between the ways cells really work and the ways that "design principles" might work.Arthur Hunt_{June 16, 2010
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Matheson allows comments at his blog, Quintessence of Dust.critter_{June 16, 2010
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Was Matheson once banned from this site? Or does he simply avoid meanaingful dialogue? The last time he was here, he left just when things started getting interesting and I never knew why. Was it our choice or his? If it is the former, why not rescind the order and allow to make his unpersuasive case right here so we can refute it?
Good idea. I have no access to the banned list. Clive or Barry might have to get involved on that one. I'd like to express my thanks to Dr. Arthur Hunt for participating here. As far as I know, Larry Moran was banned by Dave Scott, however, let me provide this Observation by Jonathan Wells regarding Moran:
And Moran’s guess that only about 5% of human genes undergo alternative splicing is flatly contradicted by 2008 articles in Nature and Nature Genetics, as well as the 2010 Nature article cited by Sternberg. In lieu of factual support for his claim, Moran ridiculed Sternberg for giving “no indication that he understands the controversy” and basing “his entire fairy tale on a value [i.e., 95%] that has been pretty much discredited.” Yet Moran provided no justification for his ex cathedra pronouncement that the 95% figure has been discredited. He simply brushed aside the 2008 and 2010 articles in Nature and Nature Genetics and their eighteen co-authors—nine of whom listed their affiliation as Moran’s own institution, the University of Toronto.
scordova_{June 16, 2010
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So, I take it my comments are deleted without any reference to their removal?
Yes. Thank you for your participation, other discussions at UD might be better suited for your comments, but not this thread. Your comment was initially put in the spam buffer by me since they repeated illogical arguments that had already been taken care of. When the comment reappered I deleted it. At this time you are still free to discuss on other threads and you can offer technical data here. Beyond that, if I find that you're repeating erroneous points that have already been refuted, as a service to readers, such comments will be edited out. Thank you however for your submissions.scordova_{June 16, 2010
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So, I take it my comments are deleted without any reference to their removal?veilsofmaya_{June 16, 2010
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Was Matheson once banned from this site? Or does he simply avoid meanaingful dialogue? The last time he was here, he left just when things started getting interesting and I never knew why. Was it our choice or his? If it is the former, why not rescind the order and allow to make his unpersuasive case right here so we can refute it?StephenB_{June 16, 2010
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Matheson: "This past week I was at a remarkable conference run by the BioLogos people, in Massachusetts near where I used to work as a postdoc. It was so refreshing to be with serious Christians who are serious about science and truth-telling." That was poor. Matheson can't defend his argument, and at the same time can't mount a deliberate distinction between discussing someone's evidence and questioning their faith. So go for broke and drag Jesus into it. Great.Upright BiPed_{June 16, 2010
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Sal, Foresight and planning. IOW not every possible splicing combination has been required. The introns not involved in splicing now are (could be) for future use if required- TBD.Joseph_{June 16, 2010
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By the way, Matheson is having a bit of a meltdown: In Matheson's Sour Grapes Whining
"3. Your Discovery Institute is a horrific mistake, an epic intellectual tragedy that is degrading the minds of those who consume its products and bringing dishonor to you and to the church. It is for good reason that Casey Luskin is held in such extreme contempt by your movement's critics, and there's something truly sick about the pattern of attacks that your operatives launched in the weeks after the Biola event. It's clear that you have a cadre of attack dogs that do this work for you, and some of them seem unconstrained by standards of integrity. I can't state this strongly enough: the Discovery Institute is a dangerous cancer on the Christian intellect, both because of its unyielding commitment to dishonesty and because of its creepy mission to undermine science itself. I'd like to see you do better, but I have no such hope for your institute. It needs to be destroyed, and I will do what I can to bring that about."
Sounds like someone expressing sour grapes after being discredited. :-) Steve needs to get spooled up on the latest literature. He could start with the paper in the Prestigious Scientific Journal Nature published May 2010: http://www.ncbi.nlm.nih.gov/pubmed/20445623 And it begins by saying:
“Transcripts from approximately 95% of multi-exon human genes are spliced in more than one way.
scordova_{June 16, 2010
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Art wrote: As I learned on the 14th of May, and in many, many past discussions, the “garbage disposal” may be a central feature of the cell, required for all manner of molecular, physiological,and organismal function, but it is not on the IDists’ radar screen.
Are you suggesting this would be a good area of investigation for ID proponents? If so, thank you for the tip. Salscordova_{June 16, 2010
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Wells’ math “adds up” only if 94,241 is the number of junctions in alternatively-spliced introns, no?
No, because there is also another line of evidence he cited.
Wells writes: scientists reported that the majority of human genes generate almost eight different messenger RNAs.
My take is worst case 50% of genes have 8 different mRNA’s. That means on worst case, on average each gene has 4 different mRNA, which implies, worst case 3 out of 4 splices are alternative splices, or 75%. So we have 20,000 genes that generate 80,000 transcripts, 60,000 of which are emerge from alternatively splicing, and we have 2 introns for each splice, that's about 120,000. Of course, I suppose it's conceiveable we have the same intron involved in two separate alternative splicings, so instead of 2 introns, we could say maybe 1.5 introns per AS, so that's 90,000 introns involved in AS. As Wells points out, this is a lower bound estimate. Thank you again for your criticism. I'm sure the readers find it substantially more astute and well reasoned than Mathesons gaffes. The Barash paper in May 2010 published in Nature also suggests that introns are integral to the read/write architecture and decoding process. Matheson is dismissive of regions that may even function as spacers (not that I'm sayin introns are only spacers). To which I respond,
many DvD's and CD's frequently have unused, blank regions. Will matheson suggest we could just physicallly remove those regions and expect a CD or DvD to function. Is it a good argument that the blank regions have no function, that have no design, or that it constitutes un-intelligent architecture? Or how about the blank spaces in bar codes, do they serve function or not. :-)
To your credit Art, you don't seem to suffer from Mathesonian illogic as much as Matheson. You strike me as far more learned and astute.scordova_{June 16, 2010
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Seeing that alternative (gene) splicing requires knowledge- what to splice, how to splice and when to splice it- how can anyone with knowledge of alternative (gene) splicing still be on the side of the blind watchmaker?Joseph_{June 16, 2010
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In his ENV piece, Wells said:
In his ENV piece, Wells states: Yet Hunt cited no scientific literature, just as Moran cited none to support his assumption that only one intron per gene may be involved in alternative splicing. Actually, a 2008 article in Science reported 94,241 splice junctions in human messenger RNAs. Since each splice requires two junctions, and humans probably have between 20,000 and 25,000 genes, this suggests an average of 2 introns per gene involved in alternative splicing.
Wells' math "adds up" only if 94,241 is the number of junctions in alternatively-spliced introns, no?Arthur Hunt_{June 16, 2010
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What Sternberg actually said: http://www.evolutionnews.org/2010/06/lets_do_the_math_again035381.html
Therefore, 22,500 genes x 7.6 introns/gene = 171,000 introns involved in alternative splicing. This is just a rough estimate, of course. And as I wrote in my original critique of Matheson, even if I’m off by a factor of two we are still left with far more functional introns than Matheson acknowledges. This compels me to ask Steve Matheson: How exactly did you come up with your estimates? And what about you, Larry Moran? What sort of arithmetic are you using?
In any case, I don't know how this can be characterized (as Art claims) to:
they believe all introns (at least all introns in genes subject to alternative splicing) are themselves alternatively spliced
Holding out the possiblity of being off by a factor of 2 hardly constitutes belief that ALL introns are involved in alternative splicing. Finally, Wells gave a pretty good alternative estimate. Any objections to Well's line of reasoning?scordova_{June 15, 2010
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Thank you Art for responding.
The suggestion that perhaps different sets of introns are subject to differential splicing in different cells or tissues is a good one.
Thank you for acknowledging this.
Art wrote: Sal, no matter how you try, you cannot twist Sternberg’s and Wells’ words to mean anything other than that they believe all introns (at least all introns in genes subject to alternative splicing) are themselves alternatively spliced.
Then please provide the specific quote from the readers where they say:
all introns (at least all introns in genes subject to alternative splicing) are themselves alternatively spliced
Further you said:
. That is why there is so much effort to argue that, in fact, all introns do undergo alternative splicing.
Who makes that argument? Not Sternberg, not Wells. Sternberg concedes the possibility that not all introns are involved in splicing:
Even if we were off by a factor of two, we would still be left with 85,500 introns that function in the process of alternative splicing.
and Wells wrote:
Since each splice requires two junctions, and humans probably have between 20,000 and 25,000 genes, this suggests an average of 2 introns per gene involved in alternative splicing. In 2009, scientists reported that the majority of human genes generate almost eight different messenger RNAs. But in order for a gene to generate eight alternatively spliced messenger RNAs it must contain at least three protein-coding segments, and thus at least two introns. So the published scientific evidence indicates that alternatively spliced genes contain at least two introns—not the one intron assumed by Moran. This would yield a lower figure than Sternberg’s original estimate—45,000, to be exact—but this is still a lot more than 1,000.
Such claims seem hardly consistent with your characterization that they insist "all introns are involved in alternative splicing". At least to your credit you're not repeating Mathesons gaffe where he argues if we don't know at this time an intron has function, then it therefore doesn't have a function. You don't have to agree with Wells and Sternberg's estimate. You may argue you are not aware of various studies that would make you agree with Wells and Sternbergs estimates. But that is not the same thing as saying we know for sure introns have no function (as Matheson asserts).scordova_{June 15, 2010
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Nothing like unrelated functions linked together, like hair color and texture, and tameness. Makes code maintenance a snap. When I worked as a programmer, I was required to make my code as cryptic and entangled as possible. I’d have been fired if I wrote something that the guy following me could understand and maintain without fear of breaking several unrelated functions.
That misconstrues what I said. I point to the readers to a common engineering practice of constructing classes that contain more instructions than the immediate need of the caller. That is the case of with overloaded methods in Java Overloaded Method There are probably hundreds of software subroutines in the operating system on your workstation that are not being used. Are you going to argue since these components aren't being used by you that they have no design for a function?scordova_{June 15, 2010
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