No rest for the SRP

matrix2Earlier in the summer, I pointed to a study that shows evidence of genome reformatting during human evolution:

In new research the Leeds team reports that a protein known as REST plays a central role in switching specific genes on and off, thereby determining how specific traits develop in offspring.

The study shows that REST controls the process by which proteins are made, following the instructions encoded in genes. It also reveals that while REST regulates a core set of genes in all vertebrates, it has also evolved to work with a greater number of genes specific to mammals, in particular in the brain – potentially playing a leading role in the evolution of our intelligence.

[…]

Says lead researcher Dr Ian Wood of the University’s Faculty of Biological Sciences: “This is the first study of the human genome to look at REST in such detail and compare the specific genes it regulates in different species. We’ve found that it works by binding to specific genetic sequences and repressing or enhancing the expression of genes associated with these sequences.

“Scientists have believed for many years that differences in the way genes are expressed into functional proteins is what differentiates one species from another and drives evolutionary change – but no-one has been able to prove it until now.”

- Here

Consider the abstract of this study:

Specific wiring of gene-regulatory networks is likely to underlie much of the phenotypic difference between species, but the extent of lineage-specific regulatory architecture remains poorly understood. The essential vertebrate transcriptional repressor REST (RE1-Silencing Transcription Factor) targets many neural genes during development of the preimplantation embryo and the central nervous system, through its cognate DNA motif, the RE1 (Repressor Element1). Here we present a comparative genomic analysis of REST recruitment in multiple species by integrating both sequence and experimental data. We use an accurate, experimentally validated Position-Specific Scoring Matrix method to identify REST binding sites in multiply aligned vertebrate genomes, allowing us to infer the evolutionary origin of each of 1,298 human RE1 elements. We validate these findings using experimental data of REST binding across the whole genomes of human and mouse. We show that one-third of human RE1s are unique to primates: These sites recruit REST in vivo, target neural genes, and are under purifying evolutionary selection. We observe a consistent and significant trend for more ancient RE1s to have higher affinity for REST than lineage-specific sites and to be more proximal to target genes. Our results lead us to propose a model where new transcription factor binding sites are constantly generated throughout the genome; thereafter, refinement of their sequence and location consolidates this remodeling of networks governing neural gene regulation.

In other words, RE1 is a piece of DNA that is spread about the genome, where it can bind the protein REST and alter the level of expression in near-by genes.  And during human evolution, RE1 may have been tweaking the expression of genes involved in brain evolution.  So why is this so interesting?

The authors note:

Emerging evidence, including that presented in this manuscript, points to highly divergent transcription factor recruitment between mammalian species. What is the basis for this divergence? Many transcription factors bind short degenerate sequences that can be readily created by single base pair mutations of a similar sequence. However, this is unlikely to be the case for transcription factors with long recognition elements, such as REST, p53 or CTCF: For simple probabilistic reasons, long periods of time must pass before long regulatory motifs can arise through DNA mutation in a given stretch of random sequence. What processes can explain the genomic remodeling of transcriptional regulatory networks observed in vertebrates?

The process of simple point mutation, ticking away over time like a clock, is insufficient for distributing these RE1 sites around the genome.  So how did they spread all over the genome?

A couple of years ago, the same researchers published a paper entitled, “Identification of the REST regulon reveals extensive transposable element-mediated binding site duplication.”  Here are some excerpts:

We reasoned that duplication and insertion by TEs [transposable elements – MG ]might be a potential mechanism of RE1 duplication. We therefore tested the duplicated RE1s for repetitive or transposon characteristics. We submitted the flanking sequences of duplicated RE1s to the online tool RepeatMasker, which indicated that the majority of duplicated RE1s are located in TEs of most major classes, including long interspersed repeats (LINEs, principally LINE2s), short interspersed repeats (SINEs, principally Alus) and hERV sequences.

[…]

Most of those sequences tested, including those associated with Alu, LINE1 and LINE2 sequences, as well as two pairs residing in non-repetitive DNA, were capable of interacting with REST.

[…]

TEs have gone through bursts of active transposition during distinct periods of evolutionary history: although LINE2 elements were thought to be active ∼200 million years ago and before human–mouse divergence, LINE1 and Alu elements continue to retrotranspose in humans. This is reflected in the phylogenetic conservation of human TE-associated RE1s: those associated with Alu and LINE1 elements have no aligned sequences other than in chimp, while a number of ancient LINE2 elements are conserved amongst multiple species.

Whoa.  The Alu elements, derived from the SRP, seemed to have been involved in spreading the RE1 elements around the genome and thus influencing brain evolution.

But it just won’t stop getting better……

[Don’t forget some related context].

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35 responses to “No rest for the SRP

  1. Hi Mike
    Let me see if I am getting anywhere with understanding your concept of front loading.
    Mainstream theory posits that for two billion years or so prokaryotes diversified. All sorts of metabolic pathways appeared to exploit various substrates as energy sources, many different environments were exploited, anaerobic, aerobic, hot, cold, salty, etc. etc. Genetic information transferred horizontally as well as vertically. Eukaryotes, sexual reproduction and multi-cellular organisms arrive later, co-option of cyano-bacteria allowing photosynthetic land plants to spread across all exploitable surfaces. similarly, co-option of Rickettsia ancestors into mitochondria by eukaryotes provided a ready-made universal energy generator. Once you have multi-cellularity and a system of growth factors and gene switches, the opportunity for variation, for example on the basic deuterostome body plan, the opportunities for variation on a theme, by the development of embryonic cells into cells having more specific function, and the growth patterns of sheets of cells into varying forms that all retain the basic topology result in the current and past diversity observed in multi-cellular organisms. The driving force behind all this is the environment, constantly varying, resulting in population explosions and extinctions as climate, continental drift, cataclysms such as volcanic eruptions, meteor strikes test the differential survivability of living organisms, in whose gene pools new random changes are occurring, disappearing or being retained, depending on the environmental selection.
    You appear not to reject this out of hand, but suggest that co-option or “pre-adaptation” is a factor. You doubt that constant random change and cumulative selection is insufficient to account for all the observed complexity at the biochemical level (the TOM complex would be an example?) and suggest that certain factors are entered into the equation of diversity by… Well here is where I get stuck, as you have told me it isn’t God. You have also told me it isn’t scientific.

  2. Mainstream theory posits that for two billion years or so prokaryotes diversified. All sorts of metabolic pathways appeared to exploit various substrates as energy sources, many different environments were exploited, anaerobic, aerobic, hot, cold, salty, etc. etc.

    Yes, and in this process, microbes were terraforming the planet – paving the way to unleash the front-loaded potential of these cells.

    Genetic information transferred horizontally as well as vertically.

    Yes, vertical transmission is the means of transferring designs across time. Horizontal transfer (which was originally resisted by proponents of the modern synthesis) is excellent design strategy to enhance the likelihood that the seeding/terraforming are successful.

    Eukaryotes, sexual reproduction and multi-cellular organisms arrive later, co-option of cyano-bacteria allowing photosynthetic land plants to spread across all exploitable surfaces. similarly, co-option of Rickettsia ancestors into mitochondria by eukaryotes provided a ready-made universal energy generator.

    Such cooption events were bound to happen, given the preadaptations that were in play. What’s fascinating is the conceptual tie-ins between these two events. These events would then serve as a nudge for the evolution of metazoan, as the prokaryotic cell could not have evolved into something that is analogous to metazoan.

    Once you have multi-cellularity and a system of growth factors and gene switches, the opportunity for variation, for example on the basic deuterostome body plan, the opportunities for variation on a theme, by the development of embryonic cells into cells having more specific function, and the growth patterns of sheets of cells into varying forms that all retain the basic topology result in the current and past diversity observed in multi-cellular organisms.

    And once again, deep homology is nudging this whole process. Consider the fact that much of the machinery needed to make neurons was in place before there were neurons.

    The driving force behind all this is the environment, constantly varying, resulting in population explosions and extinctions as climate, continental drift, cataclysms such as volcanic eruptions, meteor strikes test the differential survivability of living organisms, in whose gene pools new random changes are occurring, disappearing or being retained, depending on the environmental selection.

    You make it sound as the environment is the author (THE driving force). I say factors intrinsic to life also play a very significant role to facilitate and nudge the whole process of evolution. What’s more, the random changes that occur are under many constraints, such that life may be making intelligent use of chance.

    What you describe, Alan, can be viewed as random variation and natural selection (RV + NS). Front-loading does not deny either one. Front-loading views RV + NS as being under some form of control.

    You appear not to reject this out of hand, but suggest that co-option or “pre-adaptation” is a factor.

    Yes, front-loading depends on preadaptation – connecting future evolution with ancient designs.

    You doubt that constant random change and cumulative selection is insufficient to account for all the observed complexity at the biochemical level (the TOM complex would be an example?) and suggest that certain factors are entered into the equation of diversity by…

    It’s not a question of sufficiency or insufficiency – it’s that the more and more mainstream theory advances, the more the Duck also looks like a Rabbit.

    Well here is where I get stuck, as you have told me it isn’t God.

    If I told you this, you must be able to supply the quote where I told you this. So supply the quote.

  3. Me:

    Well here is where I get stuck, as you have told me it isn’t God.

    Mike Gene:

    If I told you this, you must be able to supply the quote where I told you this. So supply the quote.

    A pedant might say that your:

    To this, we can add your most recent comment. I wrote the word “design” and your mind heard “God.” This form of conditioning indicates a superficial approach that would be expected to exist among the closed-minded.

    does not specifically say the designer is not God. I inferred it from the statement. So is the designer God, or is God just one of many possibilities?

  4. You make it sound as the environment is the author (THE driving force). I say factors intrinsic to life also play a very significant role to facilitate and nudge the whole process of evolution. What’s more, the random changes that occur are under many constraints, such that life may be making intelligent use of chance.

    Following your link, I find

    Living things are not passive participants of the interplay between stochastic events and environmental pressures, where mutations that just happened to exist are favored in an environment that just happened to exist.

    Well, I guess this is the crux of the matter. For me, the environment is indeed the driving force and organisms are indeed passive and are being shaped by forces that they do not control. It seems you see an inference for teleology but it appears more a question of belief than evidence.

  5. BTW

    You might like to explain (or link to an explanation if there already is one) the duck rabbit thing. Presumably, it has something to do with the Rabbit-Duck illusion.

  6. Alan:

    A pedant might say

    No, that’s what a fair-minded, critical thinker would say.

    You might like to explain (or link to an explanation if there already is one) the duck rabbit thing.

    I already did.

    I pointed this out to you two weeks ago, when I wrote: “It would also help if you tried to understand the basic metaphor that underlies my whole approach.”

    Thanks for proving that you don’t pay much attention to my replies. Your closed-mindedness causes you to hallucinate about things I supposedly told you while causing you to be blind to the things I did tell you.

  7. Well, I guess this is the crux of the matter. For me, the environment is indeed the driving force and organisms are indeed passive and are being shaped by forces that they do not control. It seems you see an inference for teleology but it appears more a question of belief than evidence.

    Very good. So one crux comes into focus. The non-telic perspective maintains “the environment is indeed the driving force and organisms are indeed passive and are being shaped by forces that they do not control.” Front-loading maintains, “living things are not passive participants of the interplay between stochastic events and environmental pressures” and exert some form on control on their own evolution. Thus, evidence that living things do play an active role in their evolution is evidence of front-loading.

    It seems you see an inference for teleology but it appears more a question of belief than evidence.

    Yes, that is how it appears to you. But there is no evidence that it is more a question of belief than evidence. It’s just your belief.

  8. I am still not clear whether the front-loading hypothesis according to Mike Gene rules God in or out (or whether there are other possibilities). So is the designer God, or is God just one of many possibilities?

    I pointed this out to you two weeks ago, when I wrote: “It would also help if you tried to understand the basic metaphor that underlies my whole approach.”

    Sorry, there’s less to it than I thought. That people can interpret the same evidence in different ways is not controversial.

    Thanks for proving that you don’t pay much attention to my replies. Your closed-mindedness causes you to hallucinate about things I supposedly told you while causing you to be blind to the things I did tell you.

    Well, you didn’t tell me what role God plays in your version of reality. Initially you told me “I wrote the word “design” and your mind heard “God.” I inferred, apparently wrongly, from that that God has no part in design. So is the designer God, or is God just one of many possibilities?

    Very good. So one crux comes into focus. The non-telic perspective maintains “the environment is indeed the driving force and organisms are indeed passive and are being shaped by forces that they do not control.” Front-loading maintains, “living things are not passive participants of the interplay between stochastic events and environmental pressures” and exert some form on control on their own evolution. Thus, evidence that living things do play an active role in their evolution is evidence of front-loading.

    Well first there is no scientific evidence that organisms have shaped the environment in any foresighted way. That photosynthetic prokaryotes may have produced an oxygen-rich atmosphere is widely accepted, but to call this terraforming is wishful thinking. And your front loading concept is so amorphous that the variations on “and that is evidence for front loading” are non sequiturs.

    Me:

    It seems you see an inference for teleology but it appears more a question of belief than evidence.

    Mike Gene:

    Yes, that is how it appears to you. But there is no evidence that it is more a question of belief than evidence. It’s just your belief.

    And, unfortunately, Mike, I find the small amount of your output that I have read unpersuasive. I feel like the little boy at the parade who says” the emperor isn’t wearing any clothes”. It is small wonder to me that you find everyone that is sceptical of your concept of front loading “closed-minded”. Judging by the fact that you went to the trouble of writing and self-publishing a book and that you maintain this website, you must believe passionately in the validity of your concept. But, think how many people who were not already ID friendly for (shall we say) cultural reasons, have been persuaded. I think you are destined to remain a lone voice crying in the wilderness with regard to front loading. I find it hard to see where you have advanced beyond William Paley. Anyway, Guts was not correct in telling me that I could find real evidence for “front-loading” here, which is the reason I came to visit.

  9. Hi Alan,

    I am still not clear whether the front-loading hypothesis according to Mike Gene rules God in or out (or whether there are other possibilities). So is the designer God, or is God just one of many possibilities?

    The four-fold criteria I use to infer design cannot distinguish between a mind that is divine or one that is natural. If you have ideas about how to do this, I am all ears. Until then, any investigation that seeks to remain open-ended must acknowledge that we can neither insist the designer was God nor rule out God as the designer.

    Sorry, there’s less to it than I thought. That people can interpret the same evidence in different ways is not controversial.

    Evidence is interpreted data. That people can interpret the same data in different ways is indeed not controversial. So is that all you got from the essay? BTW, why did you ask for a link to such an essay when I provided you the link two weeks ago? Is that something I am supposed to ignore and forget?

    Well first there is no scientific evidence that organisms have shaped the environment in any foresighted way.

    We’ve been through this. I don’t know what you mean by “scientific evidence.” The last time you tried to explain this, you ended up equating science with blowing your nose.

    That photosynthetic prokaryotes may have produced an oxygen-rich atmosphere is widely accepted, but to call this terraforming is wishful thinking.

    There is no need to lash out at me like this. The hypothesis of terraforming is an example of interpreting the data in different ways, something that, as you noted, is not controversial. It is not wishful thinking in that I do not wish it to be true. It is instead a plausible interpretation and working hypothesis that intrigues me. If I don’t explore the possibility, who will?

    And your front loading concept is so amorphous that the variations on “and that is evidence for front loading” are non sequiturs.

    On the contrary, as you noted, one crux did come into focus. The non-telic perspective maintains “the environment is indeed the driving force and organisms are indeed passive and are being shaped by forces that they do not control.” Front-loading maintains, “living things are not passive participants of the interplay between stochastic events and environmental pressures” and exert some form on control on their own evolution. Thus, evidence that living things do play an active role in their evolution is evidence of front-loading. Suddenly, you back-peddle. Could this be because you are more comfortable with the notion that evidence for front-loading was supposed to be a miracle or some proof that evolution was impossible? ;)

    And, unfortunately, Mike, I find the small amount of your output that I have read unpersuasive. I feel like the little boy at the parade who says” the emperor isn’t wearing any clothes”.

    That’s okay. This was expected.

    It is small wonder to me that you find everyone that is sceptical of your concept of front loading “closed-minded”.

    Like I said, your closed-mindedness causes you to hallucinate about things I supposedly told you while causing you to be blind to the things I did tell you. No, contrary to your unsubstantiated broad-brushed misrepresentation, I don’t find everyone that is skeptical of my concept of front-loading to be closed-minded. On the contrary, if you understood the Rabbit/Duck, you should know I see an ambiguous reality that is open to more than one interpretation. Folks are free to see the Duck without being closed minded. In your case Alan, I provided plenty of evidence, independent of any front-loading argument, that led me to believe you are closed minded. Come now Alan, when you asked for a link I provided you two weeks ago, you just showed me you don’t even bother to read my replies, which was a continuation of a pattern we saw in the first thread you inhabited. You think I don’t notice behavior like that?

    Judging by the fact that you went to the trouble of writing and self-publishing a book and that you maintain this website, you must believe passionately in the validity of your concept.

    Sloppy thinking. I told you early on, “I myself am skeptical of my own views, having admitted there is a good chance I could be wrong about it all. But I obviously don’t consider my own views to be nonsense.” That I am fascinated by the topic and the possibilities, to the point where my curiosity becomes increasingly enhanced with each passing year, does not mean I “must believe passionately in the validity of [my] concept.”

    But, think how many people who were not already ID friendly for (shall we say) cultural reasons, have been persuaded. I think you are destined to remain a lone voice crying in the wilderness with regard to front loading.

    No problem. You came to this blog looking for me; I did not track you down to persuade you. If you can ever bring yourself to leave this blog, you will find that I will not hound you in some attempt to convert you. On the contrary, you will fade from my memory. Whether or not skeptics are persuaded is not important to me. What matters is whether front loading provides me a better insight into the biotic world.

    I find it hard to see where you have advanced beyond William Paley.

    And other than complaining and wanting me to know just how really, really unconvinced you are after skimming through a couple of blog entries, you have nothing else to indicate that I am wrong. Nothing.

    Anyway, Guts was not correct in telling me that I could find real evidence for “front-loading” here, which is the reason I came to visit.

    Yes, I know. You are entitled to keep the opinion you had when you first showed up – “I don’t see any evidence for front loading either.” But this constant complaining about Guts suggests you are here simply to extract some type of “payback.” You thought it important to inform me you got yourself banned from Telic Thoughts and that you are upset with that way Guts treated you. So I guess you were here all along to show Guts that he was wrong because you came here and you confirmed your preconceptions. There is no, NO, NO evidence for front-loading (or something like that).

    Fine. Now that I have walked the extra mile for you, and you have concluded Guts was not correct in telling you that you could find real evidence for “front-loading” here, are you done? Or is your vendetta bottomless?

  10. Not received any response from Profs Lithgow or Gooley. Have emailed again in case my first emails were spammed (I included a few live links)

    “Bottomless vendetta?”

    Good grief, Mike!

  11. Alan,

    When you wrote, “Anyway, Guts was not correct in telling me that I could find real evidence for “front-loading” here, which is the reason I came to visit,” you tipped your hand a little like you did when you made it clear you don’t read my replies. It’s pretty obvious you are upset with Guts because of your treatment at Telic Thoughts so you have come here to prove Guts wrong by “discovering” the preconceptions you brought with you. And that just adds another dimension to your closed mind. To acknowledge even the tiniest shred of evidence for front-loading would mean that you had to publicly agree with the guy who has “wronged” you. I don’t think that is psychologically plausible on your part. It’s one thing to express disconfirmation bias; it’s another thing to express disconfirmation bias as part of a grudge.

  12. Hey Alan,

    Not received any response from Profs Lithgow or Gooley. Have emailed again in case my first emails were spammed (I included a few live links)

    This gave me a distinct sense of deja vu. So I checked, and sure enough, we’ve danced like this before.

    About a year and a half ago, I used someone’s opinion piece to point out how some common anti-design arguments all fail against my views:

    http://telicthoughts.com/obsolete-critique/

    You replied:

    6/27

    Olegt and Steve have both pointed out that John Moore is attacking the orthodox(?) view (such as it is) of ID presented by Ben Stein in the “Expelled” movie. A quick check at Moore’s radio site has a recent interview and there are other articles by Ben Stein on ID. There is no mention of Mike Gene or “The Design Matrix” by Moore, so I have emailed him to see if he will confirm whether is is aware of you or your book and the fact that your concept of ID differs from Stein’s and the Discovery Institute. I’ll let you know if I hear anything.

    http://telicthoughts.com/obsolete-critique/#comment-196161

    A week later, you replied:

    No reply as yet. I used hotmail originally, so I mailed a reminder using my ISP account in case hotmail is looked on with suspicion. I will post any reply I receive.

    http://telicthoughts.com/obsolete-critique/#comment-196492

    Four days later, you got your reply:

    http://telicthoughts.com/obsolete-critique/#comment-196857

    Four days later, you wanted my attention:

    http://telicthoughts.com/obsolete-critique/#comment-197176

    So I replied:

    Thanks for chasing that down, Alan. It confirms the obvious, namely, that when Moore sets out to define and describe ID, he is not talking about me or my views. This explains why his claims are completely ineffective when viewed from the perspective of The Design Matrix.

    http://telicthoughts.com/obsolete-critique/#comment-197198

    You replied:

    But Mike, he was completely unaware of your perspective when he wrote his piece. It seems hardly fair to then label Moore as ineffective with his claims, as they were obviously not directed at you. Maybe you should send him a copy of your book for him to review.

    http://telicthoughts.com/obsolete-critique/#comment-197209

    So I replied:

    I did not label Moore as ineffective. I simply pointed out the fact that his claims are completely ineffective when viewed from the perspective of The Design Matrix.
    As I told Todd, you need to remember that many new eyes see this blog each day. Since Moore’s perceptions are indeed common, then the right thing to do is to periodically inform the new people that such complaints fail against my views.

    http://telicthoughts.com/obsolete-critique/#comment-197221

  13. Thanks for the links, Mike. On re-reading the thread (quickly and imperfectly), I still see things in the same way. John Moore wrote a piece critical of (shall I say) mainstream ID and you took issue with him saying his points didn’t apply to your views. Several commenters made the same point that Moore was most likely unaware of you or your blog so he could hardly be blamed for not considering your particular flavour of ID. Indeed Moore eventually responded and confirmed that he was unaware of you before he received my email.

    Anyway the fact you specifically state ID is not (yet?) scientific and should not be taught in schools means no one needs to object to you expressing your ideas about front loading. On the other hand you have to expect those who do become aware of your ideas to mention whether they are convinced by your arguments or not. I will let you know if Lithgow or Gooley do eventually reply. They also should have links to your blog so they might even comment directly.

  14. Hi Alan,

    Thanks for the links, Mike. On re-reading the thread (quickly and imperfectly), I still see things in the same way. John Moore wrote a piece critical of (shall I say) mainstream ID and you took issue with him saying his points didn’t apply to your views.

    I did not take “issue with him.” I focused on his claims, which are nothing more than claims I have heard for years:

    *ID is often referred to as Creationism light. In fact it’s more Creationism in drag.

    *Though its proponents claim scientific neutrality, they are usually overtly religious people affiliated with overtly religious institutions.

    *They have written essays and books about why ID is science.

    *And yet when all the sophistry is boiled down, the theory amounts to “living things are complicated. Some-one must have made them.”

    I simply pointed out the truth – these points all fail against my views.

    Several commenters made the same point that Moore was most likely unaware of you or your blog so he could hardly be blamed for not considering your particular flavour of ID.

    Irrelevant. I never claimed he was aware of my views, as that was not relevant when showing how these common claims fail against my views. I never blamed him for anything – I simply pointed out the truth that these claims all fail against my views.

    Indeed Moore eventually responded and confirmed that he was unaware of you before he received my email.

    Irrelevant trivia. It did not in anyway detract from the truth that those claims all fail against my views.

    Anyway the fact you specifically state ID is not (yet?) scientific and should not be taught in schools means no one needs to object to you expressing your ideas about front loading. On the other hand you have to expect those who do become aware of your ideas to mention whether they are convinced by your arguments or not.

    No problem there. Being unconvinced is not an argument against my views.

  15. …these points all fail against my views.
    …these claims all fail against my views.

    Moore was unaware of your views and was not directing any point or claim against your hypothesis. I guess he is too close-minded to search out your hypothesis before commenting on the Dembski/Behe/DI version(s) of “Intelligent Design”.

  16. BTW I just received an email from Trevor Lithgow. I am sure he won’t mind me quoting him.

    Dear Alan,

    sorry for my slow reply to your mail.

    I guess Mike Gene can claim anything he wants about our work as it sits
    in the public domain. However, in respect of his “front loading”, it is
    certainly incorrect to lay claim to our study in Curent Biology as
    supporting his theory. His theory is scientifically flawed: the premise
    that evolution is directed, controlled or guided is unfounded and with a
    flawed premise the theory should be discarded. There is no evidence (in
    our paper or elsewhere) to support the proposition that anything “would
    channel and guide subsequent evolution”.

    When we look back in time where can understand how things have evoloved,
    but evolution does not have a forward plan.

    All the best,

    Trevor

    This was in response to my email

    Hi Professor Lithgow

    I have been reading your article (Convergent Evolution of Receptors for Protein Import into Mitochondria) in Current Biology because I follow the Intelligent Design controversy and one particular blogger (designmatrix.wordpress.com) who uses the pseudonym “Mike Gene” has been posting essays referring to your paper, claiming that it supports his particular hypothesis of intelligent design which he calls front loading. In a comment to me on his blog he clarifies:
    > One formulation of the hypothesis is FLE [front loaed evolution] is: the original cells were endowed with a set of preadaptations that would channel and guide subsequent evolution. More specifically, they contained features and architecture that served as preadaptations to facilitate the evolution of multicellular, metazoan existence. The hypothesis of front-loading evolution would thus predict that significant transitions in evolution (the origin of metazoan) would depend on preadaptation.

    I don’t know if you would consider having a brief look at designmatrix.wordpress.com//2009/06/06/how-to-guide-the-blind-watchmaker/ where he makes frequent references to your work and indicate whether it indeed supports his front loading hypothesis.

    Thank you for your time
    Best regards
    Alan Fox

    PS I am writing to you again in case the live links in my last email got it spammed.

  17. Pretty much what I expected. Nothing specific, just a general dismissal.

  18. So in other words “Mike Gene shouldn’t be taken seriously because he shouldn’t be taken seriously”. I would just think he could have taken a tad more time to show HOW mike genes theory is flawed. The best I got is “There is no evidence (in
    our paper or elsewhere) to support the proposition that anything “would
    channel and guide subsequent evolution”. ” Well if MIke Gene used this guys work to support his ideas, then it would be easy for this guy to rip him a new one, but I didn’t see any actual critique other than he disagrees.

    I will admit that it was a good idea to actually contact the dude who researched this stuff to get his opinion. I have often wondered what these scientists think of the findings. Its nice to know they know of Mike Genes output and their opinion of it. Alan Fox +1, it could be +2 or even +5 if this guy had put fourth more effort to explain how Mike Gene has misconveyed the meaning of his research.

  19. Hi Alan,

    Moore was unaware of your views and was not directing any point or claim against your hypothesis.

    LOL. You seem to be under the impression that by repeating an irrelevant point, it will magically become relevant at some point. But that is not how critical thinking works, Alan. Since you think this point is relevant, you need to establish that the validity of my observations – these claims all fail against my views – is somehow dependent on Moore’s awareness.

    The fact remains that those four claims all fail against my views. Do you agree?

    I guess he is too close-minded to search out your hypothesis before commenting on the Dembski/Behe/DI version(s) of “Intelligent Design”.

    Why would you say that? There is no evidence that Moore is closed-minded.

  20. Hi Alan,
    Thanks for including your email, as I will dissect it at a later date. Let’s get to Trevor’s response to your email.

    I guess Mike Gene can claim anything he wants about our work as it sits
    in the public domain. However, in respect of his “front loading”, it is certainly incorrect to lay claim to our study in Curent Biology as supporting his theory.

    What claim? Here is the essay in question: https://designmatrix.wordpress.com/2009/06/06/how-to-guide-the-blind-watchmaker/

    Alan, can you please quote me where I claim Trevor’s study supports my theory?

    His theory is scientifically flawed: the premise that evolution is directed, controlled or guided is unfounded and with a flawed premise the theory should be discarded.

    My investigation does not begin with the premise that evolution is directed, controlled or guided. On the contrary, that is the very issue in question and the issue in question is not the premise. The issue in question is the object of investigation – Is some aspect of evolution directed, controlled or guided in some manner?

    The essay I wrote merely lays some groundwork to help us appreciate the plausibility of such a possibility. It helps us to see one way in which evolution might indeed be directed, controlled, or guided. So where is the argument that I am wrong?

    There is no evidence (in our paper or elsewhere) to support the proposition that anything “would channel and guide subsequent evolution”.

    And what type of data would count as evidence to support the proposition that anything “would channel and guide subsequent evolution?” One is left with this unanswered question because if evolution is completely unchanneled and unguided, why is convergent evolution so common, even at the molecular level? Is convergent evolution a fluke or accident?

    Even according to conventional thinking, convergent evolution teaches us that similar environments and niches can guide and channel evolution into similar solutions. We might also add that the very architecture of life guides evolution, where evolution modifies what pre-exists (think, for example, of the importance of gene duplication where past successes are guiding evolution into tinkering with them for further exploitation of untapped potentials).

    Now, let’s consider my actual arguments from the essay:

    In other words, this is an example of convergent evolution at the molecular level. Two membrane proteins independently evolved to carry out the same function. The two proteins have the same pattern of protein domains, but in reverse. Remarkable sequence similarity also exists, but again, seen only in reverse.

    So how did this occur? We can think of this example of convergent evolution as the unfolding of the preadapted state. This original preadapted state channeled the blind watchmaker, much as a seeing eye dog can lead a blind man.

    Where is the argument that shows, “NO, we can NOT think of this example as the unfolding of the preadapted state?” Why can’t we think along these lines? “But that is not how science works, Mike,” you might say. Fine, and as you know, this investigation is not science, now is it?

    So what was the preadapted state? Two key parts appear to be the original bacterial porin (which evolved to become Tom40) and the MTS-like sequences that exist on one out of every twenty bacterial proteins. Since the MTS sequence interacts with Tom40, the bacterial design was already poised to facilitate the endosymbiotic union. This interaction would set up a selection pressure that would be guided by the architecture and composition of the bacterial porin and the MTS.

    And this is wrong because…….? Are we to believe that the pre-existing MTS sequences and porins played no role in the appearance of Tom20?

    In essence, the combined demands of the porin and the MTS would function as bait to fish Tom20 out of the bacterial tool box of protein domains. Inside this toolbox was the TPR domain (a “bolt”) which seemed to fit the MTS nicely. From there, we simply attach a membrane spanning region, which could be picked up from many other bacterial proteins through duplication and recombination. In this case, natural selection did not stumble upon some solution, any solution, that just happened to work. No, no. It hit the same target – twice. And it did so roughly about the same time: after plants and animals/fungi split apart, but before animals and fungi split apart, and before green algae and plants split apart.

    And this is wrong because……..?

    Yes, Trevor shares the mainstream belief that “there is no evidence (in our paper or elsewhere) to support the proposition that anything “would channel and guide subsequent evolution.” As you yourself noted up above, Alan, “That people can interpret the same evidence in different ways is not controversial.”

    When we look back in time where can understand how things have evoloved, but evolution does not have a forward plan.

    Yet how does Trevor know this? Claiming there is ‘no evidence’ that evolution has a forward plan is not the same as claiming “evolution does not have a forward plan.” ‘No evidence’ claims do not merit such a strong truth claim.

  21. Nice reply. That quote “When we look back in time where can understand how things have evoloved, but evolution does not have a forward plan.” left a bitter taste in my mouth. Wouldn’t the forward plan be random mutation and survival of the fittest, or is that not how evolution will work in the future? I honestly think that mikes position is a hard one to describe, it is easy to get it wrong or explain it incorrectly.

  22. Mike Gene:

    LOL. You seem to be under the impression that by repeating an irrelevant point, it will magically become relevant at some point.

    I agree it’s irrelevant but, on the other hand, you resurrected the Moore thread, not me!

    The fact remains that those four claims all fail against my views. Do you agree?

    Well, were I to write a blog piece criticizing the views of Joseph Stalin and Leon Trotsky were to complain that my claims fail against his views, I might agree.

    Why would you say that? There is no evidence that Moore is closed-minded.

    I would say that because you seem inordinately fond of describing those who are unconvinced by your views as closed-minded.

    example
    example

    There are plenty more!

  23. Nelson:

    Pretty much what I expected. Nothing specific, just a general dismissal

    Just another closed-minded biochemistry professor! What is it with these guys? Anyway it’s all your fault, Nelson. If you hadn’t linked me to Mike’s blog while banning me at TT I wouldn’t ever have thought of visiting or posting here. And Mike says there is no scientific evidence of front loading to be found here! Does that make your comments at TT incorrect?

  24. Alan:

    Just another closed-minded biochemistry professor! What is it with these guys?

    Huh? You are the only one accusing Lithgow of being closed-minded, Alan. Just because you are closed-minded gives you no right to spread your mental state to others.

    Anyway it’s all your fault, Nelson. If you hadn’t linked me to Mike’s blog while banning me at TT I wouldn’t ever have thought of visiting or posting here.

    Thar da bottomless vendetta blows she does! Ahab Fox is only here to extract revenge because he feels victimized by Guts. Ahab has now confirmed my observations from above:

    But this constant complaining about Guts suggests you are here simply to extract some type of “payback.” You thought it important to inform me you got yourself banned from Telic Thoughts and that you are upset with that way Guts treated you. So I guess you were here all along to show Guts that he was wrong because you came here and you confirmed your preconceptions. There is no, NO, NO evidence for front-loading (or something like that).

    Fine. Now that I have walked the extra mile for you, and you have concluded Guts was not correct in telling you that you could find real evidence for “front-loading” here, are you done? Or is your vendetta bottomless?

    And this now becomes more true than ever:

    When you wrote, “Anyway, Guts was not correct in telling me that I could find real evidence for “front-loading” here, which is the reason I came to visit,” you tipped your hand a little like you did when you made it clear you don’t read my replies. It’s pretty obvious you are upset with Guts because of your treatment at Telic Thoughts so you have come here to prove Guts wrong by “discovering” the preconceptions you brought with you. And that just adds another dimension to your closed mind. To acknowledge even the tiniest shred of evidence for front-loading would mean that you had to publicly agree with the guy who has “wronged” you. I don’t think that is psychologically plausible on your part. It’s one thing to express disconfirmation bias; it’s another thing to express disconfirmation bias as part of a grudge.

    And please note that Ahab never denied these observations. ;)

  25. Hi Alan,

    I agree it’s irrelevant but, on the other hand, you resurrected the Moore thread, not me!

    So you confess that you do indeed repeatedly post things you know to be irrelevant. This is more evidence of a closed-mind, as one who comes to the table with an open mind would not insist on repeating points he knows to be irrelevant. Add this to the list. But let’s get to the core of the argument.

    I wrote, “The fact remains that those four claims all fail against my views. Do you agree?”

    You replied:

    Well, were I to write a blog piece criticizing the views of Joseph Stalin and Leon Trotsky were to complain that my claims fail against his views, I might agree.

    Please, no evasion by hand-waving or tap-dancing. It’s a simple yes or no question, Alan. Is it ‘yes’ or is it ‘no?’

    I would say that because you seem inordinately fond of describing those who are unconvinced by your views as closed-minded.
    example
    example

    I see. So you accused Moore of being closed-minded because you are under the delusion that I am inordinately fond of describing those who are unconvinced by my views as closed-minded. Can you explain the logic behind your confused thinking?

    As for your accusation against me, you are simply wrong (as I explained before). You have failed to come up with a single example of me describing someone as being closed-minded merely because they are unconvinced by my views. You have three candidates to draw from:

    1. Alan Fox is closed-minded. This has been determined independent of Alan being unconvinced about front-loading when he showed up on my blog. As just one example, above, Alan suggested I write about the Rabbit/Duck two weeks after I had provided him a link to an essay about the Rabbit/Duck. This clearly shows he does not read my replies. That he does not bother to read my replies (even after promising to do so) is evidence of his closed-mindedness. I have pointed this out to him twice now and twice he has ignored this. That he ignores this instead of disputing or refuting the point can be construed as tacit acknowledgement I am right. Ergo, further evidence of his closed-mind.

    2. Your first link above has nothing to do with someone responding to my views. I simply note that when person A labels person B a crackpot and a looney, it stands to reason that person A would be closed-minded about person B’s beliefs. If this is not correct, the person A should make it clear that he keeps an open-mind when it comes to crackpot and looney ideas.

    3. Your second link above likewise has nothing to do with someone responding to my views. It is about group A likening the views of group B to Holocaust denial. Given this extreme equation, it stands to reason that group A would be closed-minded to the views of group B. If this is not correct, then Group A should make it clear that we should keep an open mind about the Holocaust all being a hoax.

    Like I said, you have failed to come up with a single example of me describing someone as being closed-minded merely because they are unconvinced by my front-loading views.

    So Alan, since you bring these up, do you keep an open mind about crackpot and looney ideas? Do you keep an open mind when it comes to Holocaust denial?

    And one more thing. Even if we abandoned critical thinking and bought into Alan’s misconceptions about this, he would have three examples to point to. Okay, yet critical thinking teaches us not to cherry pick or rely on anecdotes when making sweeping claims (such as me having an inordinate fondness). I posted 1129 entries at TT and 283 here. That’s 1412 blog entries over a five year period. Let’s conservatively estimate a total of 10 replies from me per posting in the comments section, giving us 14,120 writings to sample from. Alan has three, meaning that even from his faulty perspective, he accuses me of having an inordinate fondness for a certain behavior because it allegedly exists in 0.02% of my writings. I don’t think Alan quite understands what ‘inordinate fondness’ means.

    I’m sorry Alan, but it seems to me that my informed opinion that you are closed minded has hit a raw nerve. Thus, I want your next reply to make the case that I am wrong (as maybe I am wrong). Here is what I would like to see.

    1. Summarize the evidence I have provided that you are closed-minded.

    2. Explain where and how I am wrong.

    3. Provide the evidence that you are open-minded.

    I’ll be looking forward to reading this case.

    Thanks.

  26. Here is the result of a Google search for mike Gene and closed-minded at Telic Thoughts.

  27. This may take some time but perhaps you should clarify what you mean by closed-minded. Is there a complete dichotomy between closed- and open-minded? Or is there a sliding scale between the completely gullible person who accepts everything he is told by anyone to the complete sceptic who disbelieves anything he is told by no matter who?

    And where does that get you apart from into utter distraction?

    Would it not be more productive to consider your front loading hypothesis on its merits?

    If it helps I am quite happy to confirm that my scepticism regarding your hypothesis ( i e that there is a hypothesis of front loading that is useful or interesting, that makes predictions that may be testable) is quite high.

  28. Ahab Fox is only here to extract revenge because he feels victimized by Guts.

    LMAO

  29. Alan:

    Here is the result of a Google search for mike Gene and closed-minded at Telic Thoughts.

    Hmmm. 95/14120 gets you to 0.7%. Actually, since I just discredited two of those 95, you’re down to 93. Like I said, you don’t seem to understand what ‘inordinate fondness’ means.

    But it’s even worse than that. Finding whole web pages where my name is on the same page as the words “closed” and “minded” is not evidence that I am inordinately fond of describing those who are unconvinced by my views as closed-minded. For example, many of those hits don’t involve me and many others have nothing to do with closed-mindedness:

    25 Jun 2006 … My fellow Telician Mike Gene alerted me to this short interview with historian of science … to attribute the Pope’s views to a simple-minded character named Simplicius. … Both comments and pings are currently closed.

    Like I said, you have failed to come up with a single example of me describing someone as being closed-minded merely because they were unconvinced by my front-loading views. And even if you found such a single example, it would hardly merit your claim about me having some ‘inordinate fondness.’

    This may take some time but perhaps you should clarify what you mean by closed-minded. Is there a complete dichotomy between closed- and open-minded? Or is there a sliding scale between the completely gullible person who accepts everything he is told by anyone to the complete sceptic who disbelieves anything he is told by no matter who?

    Use the dictionary. Closed-minded: having a mind firmly unreceptive to new ideas or arguments.

    Or try answering some of my questions for a change, as it should help you to begin thinking critically. For example, do you keep an open mind when it comes to Holocaust denial?

    And where does that get you apart from into utter distraction?

    Context is not a distraction, Alan. Your entire argument here is to show up, posture as some judge, and declare you see no evidence for front-loading. That’s it. And it’s all part of your bottomless vendetta against Guts. Since your entire argument centers around you, your judgment, and your obsession with proving Guts wrong, the issue of your closed-mindedness and vendetta is of huge significance.

    Would it not be more productive to consider your front loading hypothesis on its merits?

    Been doing that for years. There are over 100 substantive essays on this blog where I consider front-loading on its merits. Apart from you declaring you are not convinced after briefly skimming over a couple of them, you have no counter-arguments. You have yet to show one place where I am wrong.

    If it helps I am quite happy to confirm that my scepticism regarding your hypothesis ( i e that there is a hypothesis of front loading that is useful or interesting, that makes predictions that may be testable) is quite high.

    As expected. Given that independent evidence has shown you to be closed-minded about my views (consider the glaring example of you showing us you can’t be bothered to read my replies), one would predict you possess extreme skepticism when it comes to front-loading.
    As I noted before, “On the contrary, as you noted, one crux did come into focus. The non-telic perspective maintains “the environment is indeed the driving force and organisms are indeed passive and are being shaped by forces that they do not control.” Front-loading maintains, “living things are not passive participants of the interplay between stochastic events and environmental pressures” and exert some form on control on their own evolution. Thus, evidence that living things do play an active role in their evolution is evidence of front-loading. Suddenly, you back-peddle. Could this be because you are more comfortable with the notion that evidence for front-loading was supposed to be a miracle or some proof that evolution was impossible?”

    Since you come to the table with a closed mind and extreme skepticism, it stands to reason that you need a miracle or some proof that evolution was impossible. The problem here is that my approach will only appeal to someone with a fair and open-mind, who is sensitive to clues, and who possesses curiosity about the possibility that evolution might be under the influence of design.

  30. People you have described at Telic Thoughts as “closed-minded”:

    Genie Scott, P Z Myers, Richard Dawkins, Christopher Hitchens, Sam Harris, Aagcobb, hrun, keiths, Zachriel.

    All for excellent reasons I am sure.

  31. All for excellent reasons I am sure.

    Indeed. Readers of this blog need only consider that I have good reasons for thinking you are closed minded. Why would those be any different?

    For example, Myers, Dawkins, Hitchens, and Harris are all militant atheist activists who have a socio-political agenda. It would be highly unusual to find political activists who had an open mind about the position of their political opponents. Referring to them as being closed-minded is about as controversial as referring to Rush Limbaugh as being closed-minded about President Obama. Take Hitchens. His mind clearly links ID with religion. And what does he say about religion?

    “I think religion should be treated with ridicule, hatred and contempt, and I claim that right.”

    Religion is “sinister, dangerous and ridiculous.”

    When one adopts such a hateful, emotional position against religion, it would be absurd and irrational to insist Hitchens was open-minded about religion.

    And speaking of Aagcobb, there is a great exchange that helps to drive this point home. Since he was an attorney, I appealed to his expertise as follows:

    As an attorney, imagine you are part of a case where you are to defend Stuart Dryer, and his faculty, against the charge of being closed-minded about ID. The other side lays out the following position statement as part of the evidence: “The faculty in my department variously regard the ID crowd as insane, ignorant, dangerous, or the butt of jokes. Among our group, ID is considered a not-so-subtle cover for Christian fundamentalist creationism.” Does that hurt your case? Would you, as the attorney for Dryer et al., privately wince a little and wish such a statement was not on the records?

    Note his reply:

    If, in your hypothetical, I was trying to defend them against a charge of being close minded to ID, I would prefer that those statements didn’t exist. Of course, I don’t have to defend them against that charge, since there’s nothing particularly wrong with being close minded to ID.

    Over the last five years, I have argued with hundreds of people and commented on dozens of public figures. And yes, I did indeed find some to be closed-minded (does anyone believe closed-minded people are rare?). But that hardly supports your claim, Alan. According to you, I have this inordinate fondness of referring to people as being closed-minded simply because they are not convinced by my front-loading views. And despite being clearly motivated to show yourself to be correct, you have still not a) come up with a single example of me doing this and b) are light-years away from establishing any inordinate fondness on my part.

    Let’s summarize. I have found several lines of evidence that Alan Fox is closed minded about my views that are independent of his opinions about front-loading. Rather than refute this evidence and present evidence of his open-mindedness, Alan has retreated into an approach that seeks to paint me as someone who recklessly and consistently labels people as being closed-minded for not agreeing with my views on front-loading. In other words, he is trying to discredit me rather than deal with the evidence or arguments and he is trying to distract people from the evidence.

    Unfortunately for Alan, his attack has failed, as he has been unable to come up with one example, let alone the needed plethora of examples, of me labeling someone as closed-minded for not agreeing with my views on front-loading. And what’s worse, even if he could somehow magically come up with a large set of examples, it does not detract from the evidence of his closed-mindedness nor his inability to provide evidence of his open-mindedness.

    Ironically, it seems that Alan is being rather closed-minded about the possibility that he is closed-minded. Closed-minded squared, I guess. :)

  32. Over the last five years, I have argued with hundreds of people and commented on dozens of public figures. And yes, I did indeed find some to be closed-minded (does anyone believe closed-minded people are rare?). But that hardly supports your claim, Alan.

    Were any of these hundreds of people initially sceptical of your front loading ideas and were then persuaded that they had merit? The only reason I came to your blog was to see the scientific evidence for front loading. If Nelson hadn’t linked here, I wouldn’t have visited here. Actually, I am surprised how few times you have used the phrase “closed-minded” at TT. So I withdraw the claim.

    Unfortunately for Alan, his attack has failed, as he has been unable to come up with one example, let alone the needed plethora of examples, of me labelling someone as closed-minded for not agreeing with my views on front-loading. And what’s worse, even if he could somehow magically come up with a large set of examples, it does not detract from the evidence of his closed-mindedness nor his inability to provide evidence of his open-mindedness.

    Ironically, it seems that Alan is being rather closed-minded about the possibility that he is closed-minded. Closed-minded squared, I guess. :)

    Attack? Hardly! You are welcome to carry on as you are for as long as you want, Mike. It just seems a little, well, ineffecual. But that’s just me being closed minded.
    So, at the end of the day, along with everyone else who wasn’t predisposed to look for teleological explanations, I don’t think you have the beginnings of an argument for a front loading hypothesis, yet. You may eventually achieve the breakthrough I presume you are hoping for, time will tell, but as you don’t seem too keen on discussing front loading with me, I’ll leave you to it.

  33. “To the last, I grapple with thee; From Hell’s heart, I stab at thee; For hate’s sake, I spit my last breath at thee”

  34. but as you don’t seem too keen on discussing front loading with me, I’ll leave you to it.

    I’ll discuss front loading with anyone, Alan. But when it came to the issue of front-loading, you are the one who refused to read my arguments, backed away from a moment of agreement, and ignored my questions. Is that your idea of a discussion?

  35. Alan Said “Were any of these hundreds of people initially sceptical of your front loading ideas and were then persuaded that they had merit?”

    *raises hand* I was really skeptical of Mike Gene and front loading. I was super anti thestic-evolution till I came across his convincing arguments. Especially when I came across his positive arguments, and I did then agree that mainstream ID is too full of “this couldn’t happen” and his arguments against things like IC. In fact, I have yet to read a good argument against his views. If you know of any please point me that way! and yes I read the long boring hand waving at amazon.com

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