Ubiquitin: a challenge for evolutionary theory?

Glancing at Uncommon Descent (I still do as Denyse O’Leary often reports on interesting science articles, as here*, and the odd comment thread can still provide entertainment), I see an OP authored by gpuccio (an Italian medical doctor) entitled The Ubiquitin System: Functional Complexity and Semiosis joined together, telling the story of the ubiquitin protein and its central role in eukaryote biochemistry in some considerable detail. The subtext is that ubiquitin’s role is so widespread and diverse and conserved across all (so far known) eukaryotes, that it defies an evolutionary explanation. This appears to be yet another god-of-the-gaps argument. Who can explain ubiquitin? Take that, evolutionists! I’m not familiar with the ubiquitin system and thank gpuccio for his article (though I did note some similarities to the Wikipedia entry.

In the discussion that follows, gpuccio and others note the lack of response from ID skeptics. Gpuccio remarks:

OK, our interlocutors, as usual, are nowhere to be seen, but at least I have some true friends!

and later:

And contributions from the other side? OK, let’s me count them… Zero?

Well, I can think of a few reasons why the comment thread lacks representatives from “the other side” (presumably those who are in general agreement with mainstream evolutionary biology). 

  1. In a sense, there’s little in gpuccio’s opening post to argue over. It’s a description of a biochemical system first elucidated in the late seventies and into the early eighties. The pioneering work was done by Aaron Ciechanover, Avram Hershko, Irwin Rose (later to win the Nobel prize for chemistry, credited with “the discovery of ubiquitin-mediated protein degradation”, all mainstream scientists.
  2. Gpuccio hints at the complexity of the system and the “semiotic” aspects. It seems like another god-of-the-gaps argument. Wow, look at the complexity! How could this possibly have evolved! Therefore ID!  What might get the attention of science is some theory or hypothesis that could be an alternative, testable explanation for the ubiquitin system. That is not to be found in gpuccio’s OP or subsequent comments.
  3. Uncommon Descent has an unenviable history on treatment of ID skeptics and their comments. Those who are still able to comment at UD risk the hard work involved in preparing a substantive comment being wasted as comments may never appear or are subsequently deleted and accounts arbitrarily closed.

I’m sure others can add to the list. So I’d like to suggest to gpuccio that he should bring his ideas here if he would like them challenged. If he likes, he can repost his article as an OP here. I guarantee that he (and any other UD regulars who’d like to join in) will be able to  participate here without fear of material being deleted or comment privileges being arbitrarily suspended.

Come on, gpuccio. What have you got to lose?

906 thoughts on “Ubiquitin: a challenge for evolutionary theory?

  1. Erik: I don’t see how you can easily part with either one of them [common descent and natural selection]. They are both integral to evolution as conceived by Darwin.

    It’s even more ambitious! For evolution by common descent with modification by natural selection to be correct, there has to be an unbroken line of descent between every extant and extinct organism via viable intermediates back to the last universal common ancestor. That’s a lot to shoot at.

    But as others have said, so far there’s no better explanation for the evidence we see.

  2. Entropy:
    CharlieM,

    I suspect that you didn’t understand the problem. Can you state what you think I meant? Just to understand where the explanation might have gone wrong.

    I only reasonable meaning that I could gather from your words were that it is not possible to have a hierarchy of designers and designed entities. And if that is the case I do not follow your logic.

    I look forward to your clarification.

  3. Alan Fox: It’s even more ambitious! For evolution by common descent with modification by natural selection to be correct, there has to be an unbroken line of descent between every extant and extinct organism via viable intermediates back to the last universal common ancestor. That’s a lot to shoot at.

    But as others have said, so far there’s no better explanation for the evidence we see.

    There’s no equal explanation for the evidence that we see.

    Anything else is ad hoc, including any “evolution by design.”

    Glen Davidson

  4. GlenDavidson: There’s no equal explanation for the evidence that we see.

    True enough. And “Intelligent Design” doesn’t qualify as an explanation at all!

  5. Alan Fox: It’s even more ambitious! For evolution by common descent with modification by natural selection to be correct, there has to be an unbroken line of descent between every extant and extinct organism via viable intermediates back to the last universal common ancestor. That’s a lot to shoot at.

    It’s pretty much necessary that all Eucarya be cousins. Bananas, humans, and so forth.

    It’s still possible that abiogenesis occurred more than once.

  6. dazz quotes gpuccio:

    500 bits means: a specific sequence of 500 binary values, or of 150 specific decimal values, or of 115 specific AAs (base 20) that is necessary to implement one specific function.

    It’s like having a number like this:

    639467265010436782y3952223904758…

    150 figures long, which is the unique key to an electronic safe, and trying to divine it by RV and NS:

    a) RV: we just try any sequence of 150 figures

    b) NS: after seeing it does not work, we change a figure at a time, and we test if there is any increase in the (non) function.

    It’s not like we haven’t been over this before.
    Sigh.
    Between this and colewd’s awesome riposte:

    Entropy:

    That’s but one of the many things. It doesn’t tell you the amount of sequence variants within the family that could still do the job. It doesn’t tell you if other protein families could have done the job.

    colewd:

    The problem is that many proteins have to work together. Whether or not other proteins could do the job does not materially help evolvability unless your claim is almost any group of proteins will perform this function. This is a testable claim.

    I think we have distilled the inanity.

  7. petrushka: It’s still possible that abiogenesis occurred more than once.

    But no survivors survive from any but the event with survivors. Of course the universe could be teeming with life, too.

  8. DNA_Jock: It’s like having a number like this:

    639467265010436782y3952223904758…

    150 figures long, which is the unique key to an electronic safe, and trying to divine it by RV and NS:

    a) RV: we just try any sequence of 150 figures

    b) NS: after seeing it does not work, we change a figure at a time, and we test if there is any increase in the (non) function.

    It’s not like we haven’t been over this before.
    Sigh.

    > is.number(639467265010436782y3952223904758)
    Error: unexpected symbol in “is.number(639467265010436782y3952223904758”
    Rebooting universe

  9. Corneel,
    Lovely data on the promiscuity of the E3 ligases. That pretty much deep-sixes colewd’s argument.

    I am also enjoying gpuccio’s false dichotomy between “change one AA at a time” and shuffling protein domains, like there’s nothing possible in between. Then, “I’ll focus exclusively on the former, because the math is less impossible…” add a nice dollop of personal incredulity and hey presto, we’re there: Evolution is impossible!

  10. Corneel: b) NS: after seeing it does not work, we change a figure at a time, and we test if there is any increase in the (non) function.

    In living things, all the existing numbers open the safe. Some variations on the number also open the safe.

  11. DNA_Jock: Lovely data on the promiscuity of the E3 ligases. That pretty much deep-sixes colewd’s argument.

    Thanks, but I think most credit goes to Entropy. I just followed up on his lactate dehydrogenase example 🙂

  12. It’s more like we have a 150 digit string that opens the safe, and some digits can be changed to other digits and still open the safe.

    Not just that, but after a digit has changed, DIFFERENT digits can be changed and still open the safe.

  13. Alan Fox: But no survivors survive from any but the event with survivors. Of course the universe could be teeming with life, too.

    Depends on what you mean by survivors. Genes might survive being ingested.

  14. No need to reboot the universe, Corneel, since “639467265010436782y3952223904758” is clearly designed.
    The probability that a randomly generated 32-element alphanumeric string would contain one (or fewer) letters is 1.33e-16.

    Well, that or he’s not using a German keyboard.

    I’m going to go with “designed”.

    </creationist>

  15. Corneel: Rebooting universe

    I get a message that it’s installing updates now. Buckle up guys, some weird shit is about to happen

  16. DNA_Jock,

    Lovely data on the promiscuity of the E3 ligases. That pretty much deep-sixes colewd’s argument.

    Im sorry Jock, how many different molecules does a single E3 have to bind with? How many E3 configurations are there?

  17. Alan Fox,

    But as others have said, so far there’s no better explanation for the evidence we see.

    There are two explanations one is mis leading and other is not.
    -built by blind unguided processes
    -designed

    One helps you understand biology the other misleads you. If you study disease and the deregulation of the ubiquitin system as a cause only one will make sense to you.

  18. colewd: There are two explanations one is mis leading and other is not.
    -built by blind unguided processes
    -designed

    One helps you understand biology the other misleads you. If you study disease and the deregulation of the ubiquitin system as a cause only one will make sense to you.

    That’s right!
    And that’s why drug developers focus exclusively on the non-design explanation!
    Remember, they are not tied to the Darwinist omerta, they just care about making money.

  19. colewd,

    colewd: Im sorry Jock, how many different molecules does a single E3 have to bind with? How many E3 configurations are there?

    I’m very sorry, Bill. but how many different E3 sequences could bind to each target? How many potential E3 configurations are there?
    YOU are the one who is trying to put a number on this. Well, you are pretending that the number is one, and then sticking your fingers in your ears, I guess.

  20. DNA_Jock,

    YOU are the one who is trying to put a number on this. Well, you are pretending that the number is one, and then sticking your fingers in your ears, I guess.

    Lovely data on the promiscuity of the E3 ligases. That pretty much deep-sixes colewd’s argument.

    You were trying to declare victory and go home with one piece of data.

    Are you ready to make a real argument that the paper that Corneel referenced really shows that the ubiquitin system is evolvable?

  21. DNA_Jock,

    Remember, they are not tied to the Darwinist omertà, they just care about making money.

    Some have been but as they clear this nonsense out of their minds real progress is being made like the discovery of the ubiquitin system and how its deregulation causes many known human diseases.

  22. Entropy wrote:

    We humans, the very designers used as “models” to “infer” design, would not survive without ubiquitin systems. So, they’re proposing that the systems that make a designer were designed.

    CharlieM replied:

    CharlieM: I only reasonable meaning that I could gather from your words were that it is not possible to have a hierarchy of designers and designed entities. And if that is the case I do not follow your logic.

    I understood Entropy to be referring to the bootstrap problem: it is our universal experience that designers are made out of meat.
    Arguing that designers are necessary to create the first animal is, therefore, problematic.
    Hence all the finessing about disembodied intelligences, which have never, I think you will agree, been observed to do anything.

  23. colewd: You were trying to declare victory and go home with one piece of data.

    Are you ready to make a real argument that the paper that Corneel referenced really shows that the ubiquitin system is evolvable?

    Try reading my comment for comprehension. I was not declaring victory, merely pointing out that your argument doesn’t hold water. At all.
    So we are back at “don’t know”.

    Regarding researchers working on ubiquitin, you wrote:

    colewd: Some have been but as they clear this nonsense out of their minds real progress is being made like the discovery of the ubiquitin system and how its deregulation causes many known human diseases.

    LOL
    Really? You’re claiming that the researchers uncovering the ubiquitin system are assuming that the system was designed?
    Citations, please.
    I can say with some certainty that Hugh Pelham and Mariann Bienz reckon it’s the result of evolution.

  24. DNA_Jock,

    Try reading my comment for comprehension. I was not declaring victory, merely pointing out that your argument doesn’t hold water. At all.
    So we are back at “don’t know”.

    You made an unsupported assertion. You have not shown at all that my argument doesn’t “hold water”. The promiscuity of the U3 proteins on to a single substrate does not even begin to address my argument to Entropy. How about other substrates, how about binding ATP, Ubiquitin, U1 and U2. You have made an argument from ignorance. Get educated.

  25. DNA_Jock,

    The Nedd4 family of HECT domain–containing E3 ligases ubiquitinate many transcription factors and signaling proteins, and their activity is tightly regulated. Normally, intramolecular interactions curb the catalytic activity of the HECT domain, but these can be broken by the binding of PY motifs, found on substrate molecules and adaptors, to the WW domains characteristic of this E3 ligase family. This raises the prospect of substrates automatically activating the ligases, frustrating the purpose of ligase regulation. Here we show that soluble protein substrates and adaptors such as α arrestins, even with multiple PY elements, cannot activate ligase activity efficiently. However, we found that polymerization or membrane tethering of these substrates dramatically increases the ligase activity both in vivo and in vitro. Aggregation of luciferase-containing substrates upon heat shock had a similar effect and could also expose cryptic PY elements in the substrates. We inferred that ligase activation critically requires a substantial array of clustered PY motifs and that the formation of such arrays on membranes or in polymeric aggregates may be an essential step in this mode of ligase regulation. We conclude that recruitment of α arrestins to membrane receptors and aggregation of unstable proteins after heat shock may be physiologically relevant mechanisms for triggering ubiquitination by Nedd4 family HECT domain–containing E3 ligases.

    Is this the paper you are talking about? Where is the evolution of ubiquitin system discussed?

  26. DNA_Jock: Really? You’re claiming that the researchers uncovering the ubiquitin system are assuming that the system was designed?

    colewd has a specific, single example of where assuming “design” supposedly “helped” him discover something in his work. I think that’s what he’s referring to.

    The simple fact is that if simply “assuming Intelligent Design” was more productive in science it would have never stopped being done.

  27. OMagain,

    colewd has a specific, single example of where assuming “design” supposedly “helped” him discover something in his work. I think that’s what he’s referring to.

    The simple fact is that if simply “assuming Intelligent Design” was more productive in science it would have never stopped being done.

    You are right on this one. What I discovered from bottom up research is that cell division (also stem cell) and vascular growth were controlled by the ubiquitin system. The same system that was initiating a tumor, by increasing transcription rates through loss of control, was also causing it to metastasize by building a bridge to the blood stream. Understand biology is partially about understand system “design”.

    Cancer researches are making progress by understanding this “design”. This helped initiate the introduction of proteasome inhibitors for multiple myeloma.

  28. A sample of the biological design hypothesis:

    Abstract
    In the field of synthetic biology, genetic networks are designed by combining well-characterized genetic parts, similar to electronic circuits. Such gene networks are called synthetic genetic circuits. The design approach for synthetic genetic circuits is based on mathematical modeling and numerical simulation. The approach allows the realization of various cellular functions. However, unavoidable differences in the initial states or fluctuations of the gene expression in cells have prevented the precise prediction and control of cellular behavior. Therefore, the design of synthetic genetic circuits is not sufficient, and the dynamic control of the circuits is also required. In this report, we provide examples of synthetic circuit designs and the control of synthetic biological systems, as well as perspectives on design and control.

    Notice the phrase “control of the system”. The ubiquitin system fits this very well.

  29. colewd: You made an unsupported assertion. You have not shown at all that my argument doesn’t “hold water”. The promiscuity of the U3 proteins on to a single substrate does not even begin to address my argument to Entropy. How about other substrates, how about binding ATP, Ubiquitin, U1 and U2. You have made an argument from ignorance. Get educated.

    Strange. I had seconded Entropy’s argument thus

    In addition to Entropy’s excellent points [in particular the point that “it is not possible to know how many variants would work just as well, and we cannot know how many other protein families could have done the work.” which is unassailable, and deep-sixes any attempt to calculate p(T|H) ]

    and pointed out the difference in constraint between optimized proteins and “younger” proteins.
    You responded

    There is no evidence of another peak relative to the proteins that make up the complexes. With multi protein complexes the proteins become specifically defined based on the other proteins in the complex. I know you understand this. In the ubiquitin complex case, the E3 protein must bind to E2, ubiquitin and the target protein for destruction or other targets.
    We have no evidence that any exploration has occurred only speculation. We have no evidence of another peak only speculation.
    We have evidence that in its current configuration that exploration is extremely limited.
    This is strong support for the design inference.

    Corneel’s reference notes:

    Any particular substrate may be targeted by multiple E3 ligases at different sites, and a single E3 ligase may target multiple substrates under different conditions or in different cellular compartments.

    I noted that this deep-sixes your argument. That’s not an unsupported assertion. It’s a supported assertion. Learn the difference.
    You mentioned binding ATP. That’s quite the own goal: we KNOW that there’s multiple ways of doing that.

  30. colewd: . What I discovered from bottom up research is that cell division (also stem cell) and vascular growth were controlled by the ubiquitin system.

    Did you start out assuming cell division was uncontrolled? Why would the conclusion of “design” not be equally as valid were something else to be controlling those things? What could cell division be controlled by that would not cause you to conclude “design”?

    colewd: Cancer researches are making progress by understanding this “design”.

    Why have you scare quoted “design” there?

    colewd: Notice the phrase “control of the system”. The ubiquitin system fits this very well.

    As noted above, did you start out thinking that cell division was uncontrolled and unconstrained?

  31. DNA_Jock: That’s quite the own goal: we KNOW that there’s multiple ways of doing that.

    It always amuses me to ask “which one?” when IDists proclaim that the bacterial flagellum was designed.

    Will it be scales or spines tonight Sir?

  32. colewd: Is this the paper you are talking about? Where is the evolution of ubiquitin system discussed?

    Silly Billy. You claimed, in reference to the non-design explanation, that

    Some have been but as they clear this nonsense out of their minds real progress is being made like the discovery of the ubiquitin system and how its deregulation causes many known human diseases.

    I replied

    Really? You’re claiming that the researchers uncovering the ubiquitin system are assuming that the system was designed?
    Citations, please.
    I can say with some certainty that Hugh Pelham and Mariann Bienz reckon it’s the result of evolution.

    The pubmed search link was to show you that they are productive in the field.
    Do you have any citations for productive researchers who reckon that it is designed? Or were you only referring to yourself? In which case…

  33. DNA_Jock,

    We have no evidence that any exploration has occurred only speculation.

    You think you have provided evidence that exploration has occurred.

    You are contradicting your own argument that current observation tells us nothing about history.

    Cornell is explaining E3’s current function. And yes I would guess that binding flexibility would be important to this design as most all nuclear proteins are involved.

    The pubmed search link was to show you that they are productive in the field.

    Your citation did not support your claim. There are speculative papers on the subject. You can find them with a google search.

  34. OMagain,

    Did you start out assuming cell division was uncontrolled?

    No. I started out trying to find out why low blood levels of a small molecule were dramatically increasing cancer risk. I had no idea how cell division was controlled at that time.

  35. DNA_Jock,

    Really? You’re claiming that the researchers uncovering the ubiquitin system are assuming that the system was designed?

    This is your straw-man. Why do fell compelled to create one at this point?

  36. colewd: I had no idea how cell division was controlled at that time.

    Why would the conclusion of “design” not be equally as valid were something else to be controlling cell division? What could cell division be controlled by that would not cause you to conclude “design”?

  37. colewd: I had no idea how cell division was controlled at that time.

    At that time, had you concluded that cells were designed?

  38. gpuccio:

    The idea of neo-darwinism is that a complex function (like ATP synthase) should come into existence through hundreds of specific mutations in the same structure which in the end build the function as we observe it today.

    Pow! Pow!

  39. DNA_Jock,

    You mentioned binding ATP. That’s quite the own goal: we KNOW that there’s multiple ways of doing that.

    There you go again. Declare victory and go home with a silly claim that is irrelevant to the discussion. I am going to part here until you can make a serious argument about the evolvability of the ubiquitin system.

  40. colewd: I going to part here until you can make a serious argument about the evolvability of the ubiquitin system.

    It’s kind of the point actually. Multiple ways of doing similar things is the ladder.

  41. OMagain,

    At that time, had you concluded that cells were designed?

    Not at that point. It was not relevant to the research as I understood it at the time.

  42. colewd: Not at that point. It was not relevant to the research as I understood it at the time.

    So, was it finding that cell division was controlled that led you to conclude design? If so, why would the conclusion of “design” not be equally as valid were something else to be controlling cell division? What could cell division be controlled by that would not cause you to conclude “design”?

  43. colewd: You think you have provided evidence that exploration has occurred.

    Well, given that multiple different ligases can address the same protein target, and multiple different protein targets can be addressed by each ligase, I think that your claim

    With multi protein complexes the proteins become specifically defined based on the other proteins in the complex…We have no evidence of another peak only speculation.

    is looking unwell.
    You’ve suddenly decided that “binding flexibility would be important to this design”. And you think that I am contradicting my own argument? ROFL

  44. OMagain,

    It’s kind of the point actually. Multiple ways of doing similar things is the ladder.

    You’re looking at the design of a single protein. The adaptive immune system uses hypermutation to create new antibodies. Thats another function that emulates evolution but is specifically designed with a very small substrate (about 10 AA long) which limits the search space. These are specific designed systems that tell us nothing about their origin.

    The ladder is one protein making a step by step journey to a new function. How can it do this without falling into the abyss of sequence space unless the ladder is designed?

  45. DNA_Jock,

    With multi protein complexes the proteins become specifically defined based on the other proteins in the complex…We have no evidence of another peak only speculation.

    Where have you or Corneel demonstrated another Peak? You’re continuing to double down on your poor analogy and still have not made progress convincing anyone that the ubiquitin system evolved.

    So you’re trying to claim protein binding flexibility is evidence that another peak exists? I have to admit your skill set is impressive trying to escape your own self contradiction.

    Maybe your daughter can help you here:-)

  46. Erik: Corneel: For example, an important microevolutionary topic is the origin of adaptations. Let me assure you that transformist explanations were not warmly greeted pre-Darwin.

    Those topics were noted and covered ever since Aristotle at least. Not sure how warmly greeted you want it to be.

    You claimed microevolution was “common knowledge and accepted by everyone”. That’s a far cry from a few philosophers noting that species were not fixed. You are also ignoring the fact that these notions were denounced as pagan when Christianity swept over the ancient world.

  47. gpuccio@UD

    Corneel at TSZ:

    Thank you for signaling the typo. I have just deleted the “y”! 🙂

    I am a bad monkey. No Shakespeare from me, certainly! 🙂

    Oooh excellent. Your sense of humor is much better than ETs 🙂

    ETA: will address the other comments later. It’s getting late for me.

  48. gpuccio@UD

    Me: So why would the protein coding genes not be representative of all evolutionary transmitted information? I trust that you have a scientific and empirical argument for doubting this.

    Yes. By far the most important argument is that I don’t believe that the structure of the complex nervous system in humans, in particular the brain, and its exclusive new potentialities, can derive from a very small change in protein coding genes. For that, even the changes in regulatory non coding sequences seem to be insufficient.

    It is not entirely surprising to see you packaging both human exceptionalism and personal incredulity into a single sentence. But this argument is neither scientific nor empirical, don’t you agree?

  49. gpuccio@UD

    So, we have 600+ E3 ligases which are completely different one from the other at sequence level (except for the shraed, small domains, as explained).

    For starters: I don’t believe that the substrate binding domains of all those 600+ E3 ligases are completely unrelated. You better bring some evidence to the table for that claim.

    So, it’s not so much redundancy, as multiplicity. Different E3 ligases may target a same protein, but at different sites. Specificity, again.

    LOL, you make exactly the same 180 degree turn that Bill Cole made at TSZ. What’s that? E3 ligases are not specific but promiscuous? NO! They are flexible, they have multiplicity. If E3 ligases have great specificity then that is evidence of Design, and if they bind a shitload of different proteins then that is also evidence of Design. So what isn’t evidence of Design?

    You say that they are “promiscuous”. But the authors have different conclusions, and I agree fully with them:

    “This drives a huge diversity in spatial and temporal control of ubiquitylation (reviewed by ref. [61]). Cellular context is an important consideration, as substrate–ligase pairs identified by biochemical methods may not be expressed or interact in the same sub-cellular compartment.”

    IOWs, there is a huge diversity of strict control: IOWs, huge functional complexity.

    Promiscuous? Do you know how that is called? It’s called “cross-talk”. A term that we have found consistently in the scientific literature about the ubiquitin system.

    This is so typical of the everything-must-be-designed ID bias. If this is true, then why would the authors consider this a challenge for detecting valid substrates? Better read that part again:

    Cellular context is an important consideration, as substrate–ligase pairs identified by biochemical methods may not be expressed or interact in the same sub-cellular compartment.

    Many of the substrate-ligase interactions detected in vitro do not occur in vivo because the substrate and the ligase are not co-expressed! What the authors are saying is that a large part of the substrate-ligand pairs that were identified are expected to be spurious. That is why the paper has a paragraph dedicated to the validation of the candidates found by high-throughput methods. That completely undermines your claim that all of this is “cross-talk”,”strict control” or “complexity, at the highest level”. Patent nonsense.

    And now you need to face up to the fact that the issue of protein promiscuity, as raised by Entropy, is a valid answer to your challenge:

    1) Is there any conceptual reason why we should believe that complex protein functions can be deconstructed into simpler, naturally selectable steps? That such a ladder exists, in general, or even in specific cases?

    To which the answer now must be “yes” with respect to the substrate specificity of E3 ligases.

  50. Corneel, to gpuccio:

    If E3 ligases have great specificity then that is evidence of Design, and if they bind a shitload of different proteins then that is also evidence of Design. So what isn’t evidence of Design?

    The lame arguments of Pooch and Bill. They aren’t designed, but instead evolve by a series of goalpost moves. 🙂

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