Brian Miller: Co-option and Irreducible Complexity

How do you determine that a protein has no function? That’s the first big problem. There are millions of possible substrates that a protein can interact with, so how do you determine if a protein has no function if you don’t test it against all possible substrates? This is one of the major failings of ID arguments. They blindly assume that a protein can only ever have one function. For example, Douglas Axe tested tested for beta-lactamase activity in his mutated proteins as if beta-lactams are the only substrate that exists in nature. After testing these proteins against just one substrate out of millions he declared they had no function. That makes no sense.

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sure that it may be possible. depend on the protein and the function we are talking about. its also depend on creature.

it’s not only possible, they EXIST IN NATURE.

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Of course. Which experts?

That’s odd, as I was using them as a very large example of how you were grossly misrepresenting what is known (“all evidence”) about the prevalence of function in protein sequence space, not as “understanding the active sites of proteins.” Where did that even come from?

Indeed they are different, and that is obviously because they are highly constrained and must fit into the framework of an immunoglobulin fold (note, Brian, this is how real biologists use the term “fold”). The active site is like a pair of lips, while most unconstrained enzymes have pockets for their substrates.

You’re really missing the fact that this difference doesn’t help you, because it means that the 10^-8 frequency we see with catalytic antibody screens is a gross underestimate of the frequency with unconstrained proteins.

I see an actual testable hypothesis there, Brian. Do you?

These are true enzymes. They have lower activity because they are highly structurally constrained. Do you see the testable hypothesis yet?

No, it isn’t, as you didn’t even mention function!

The challenge is getting you to use the same terminology people in the field do.

We know with absolute certainty that the structural classification “folds” doesn’t correspond to activities. And you’re fudging by pretending that catalytic antibodies are mere binding sites. Do you even realize that binding is pretty much the basis of catalysis?

What’s the difference between a “complex fold structure,” a “fold structure,” a “fold,” and a “structure”? You’re tying yourself into semantic knots to avoid confronting the simple fact that function is easy to find in random sequence space, about one in 10^8 in literally hundreds of independent trials, even when we dramatically constrain the size and the supporting structure of the random sequences being screened.

Please explain how a single backwards model in which enzymatic activity was never even measured trumps this giant mass of evidence.

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This is my assessment as well.

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Proteins are essential components for molecular machines, so they represent predefined general targets in amino acid sequence space. A minimum set required to create a molecular machine or other structure would be a more specific target. These targets might never be realized, or they might be found in some organism at some time in history. The challenge is that finding even one protein of a size comparable to a larger flagellar protein would require for 1E132 distinct protein possibilities to exist. I would be interested to see any expert who has ever claimed they are that abundant.

In addition, for evolution to serendipitously stumble across complex molecular machines, the search space would have to be filled with functional possibilities. In other words, vast numbers of other possible configurations of proteins corresponding to locomotive machines must be possible for any to be found. However, if so many possibilities exist, the chances of finding a solution which matches a human-designed outboard rotary motor so closely is nil.

However, if so few solutions exist in both the search space for human engineering and for biological systems that such similar designs appear in both engineering and biology, then the chances of nature stumbling upon one of them is nil, since functional combinations would be so rare. In summary, the fact that the flagellum matches so closely with a known design logic means that it can better be understood as a predefined target corresponding to a rotary motor than a haphazardly fit together collection of proteins which just happened to function as a motor.

Natural selection cannot help add even a single piece to the motor, such as the filament, since adding the piece requires multiple highly-specialized proteins. Until all appear and are then fully integrated into the assembly process, natural selection would work against adding the filament. The production of a useless protein wastes resources and would be quickly disabled through mutations.

You might try to argue that each protein (filament, assembly cap, 2 joint proteins) served some other role, but the degree of specialization makes such a possibility difficult to justify. And, even if they did play some specific role in some other context, selection would prevent them from being redirected toward a completely different process.

A useful exercise would be attempting to devise or find a semi-detailed scenario for the evolutionary development of any complex, highly-integrated multi-protein structure. Any realistic attempt would run into these challenges.

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Silly strawman alert! Evolution didn’t “stumble across” complex molecular machines. The evidence shows complex molecular machines evolved from simpler ones through known processes involving random genetic changes and selection feedback.

Bacterial flagella (and there are many different ones) don’t resemble human designed outboard motors at all except in the most superficial way of function - they propel an object through a fluid.

Another episode of personal incredulity theater. Yawn.

I notice you didn’t address a single one of the many problems with your claims which were pointed out in lieu of just repeating the same discredited ID talking points. Why is that?

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This makes no sense. If there are any “targets” in sequence space, they would be functions, not proteins.

Evolution doesn’t work that way.

I’d like to see the evidence supporting that number. “All evidence,” as you would say. :wink:

That probably depends on the antecedent of “they,” which appears to be word salad.

But I’m a scientist, so I’m interested in the evidence instead of claims. Why aren’t you?

Who were the experts with whom you discussed catalytic antibodies?

No one who understands biology thinks or says that evolution does that. Have you heard of selection?

That’s why I pointed you to catalytic antibodies. They show that sequence space has much more function than you claim it does.

And how many molecular motors will one find in the typical mammalian cell? If you’d like to consult with a real expert on that, it would be me. :sunglasses:

This is another problem with the ID misrepresentation of one flagellum as the only one. How many non-homologous flagella are there in biology, Brian Miller?

And the one of many you are misleadingly using the singular definite article for does not “match.”

Here’s a question: which of the multiple flagella is the closest analog of a human-designed outboard motor?

This is factually, objectively, empirically false, and has been shown to be at least hundreds, probably thousands, of times. Heck, I’ve shown it for two different genes pretty much by myself!

What drives this arrogance that leads you pontificate when you ignore so much of the evidence, and to pretend that you understand more than those who have spent entire careers studying biology?

Can you see the testable hypothesis that I mentioned above, Brian?

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I wholehearted agree with you Brian Miller. I have been accused of being a liar on several occasions on this website and have been snubbed for choosing to trust in the Intelligence of a Great God whom I believe has Spoken His Word over the guesswork of man. I dont know if it encourages you or not to receive my applause and encouragement to press on in your work but there you go anyway. I believe that folks like yourself, Gauger, Pearcey, Meyer, Wise, Behe, Jeanson, others are historical scientists who take a far more balanced and worthy approach for figuring our beginnings. Others who are the very ones who seem disinterested to learn from that list of individuals because it seems that they have pre concluded that naturalism is the only lense to see through which has necessarily created results exactly in proportion to the pre conceived notion. They miss the forest. The more i put an ear to the soundbites coming from your camp constrasted to theirs, i must wholeheartedly applaud you! So keep up the good work. It may be useless trying to do any pursuading here, but your voice is valuable especially for the younger generations. Thankyou.

They aren’t predefined. Beneficial changes in DNA sequence are selected for after they appear. This is one of the biggest mistakes that ID supporters make. They act as if the proteins evolution found are the only proteins that could have evolved. This is simply false. The eukaryotic flagellum demonstrates this in spades since the eukaryotic version shares no homology with the prokaryotic flagellum. Very different amino acid sequences both result in the same function.

The challenge for ID supporters is to calculate the number of possible proteins that could result in a motility system, and then support their claim that these systems could not evolve. They have yet to do that.

Where is the evidence that precursors to flagellar proteins could not have functioned outside of the flagellum?

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I’m very interested to hear your method for doing scientific research which doesn’t rely 100% on naturalism for reliable and repeatable results. How do you test a new vaccine when you have to allow for a supernatural Loki God making it 100% effective one day and a deadly poison the next?

The people who complain the loudest about naturalism based science never offer any practical alternatives.

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I think it is worth pointing out that the Bible was written by men, and is being interpretted by us humans as well.

It is ID supporters that want to call Intelligent Design a scientific theory. They want the banner of science attached to their claims. Science requires methodological naturalism, and there is no way around it. If you reject the use of methodological naturalism then it is best to admit that Intelligent Design is not scientific.

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No, they represent potential contributing factors in the space of potential solutions to the circumstantial challenges of survival and reproduction. They’re not targets. They are contingent outcomes of extremely long lineages of blindly samling a huge space of different possible solutions to the problem of survival and reproduction.

A minimum set required to create a molecular machine or other structure would be a more specific target. These targets might never be realized, or they might be found in some organism at some time in history. The challenge is that finding even one protein of a size comparable to a larger flagellar protein would require for 1E132 distinct protein possibilities to exist.

It’s not clear to me why that would be a problem. Can you explain how, if that number is actually required, that would be a problem? Are you saying that, if the average flagellum protein is (say) 300 amino acids long, in order for such a protein to evolve, there would have to be 10^132 functional proteins in that space?

In addition, for evolution to serendipitously stumble across complex molecular machines, the search space would have to be filled with functional possibilities.

Well, yes, and every line of evidence corroborates that being the case. Take a look at the Long-Term Evolution-Experiment with E coli. Pick one of the lineages that has been evolving about 65.000 generations. IIRC something like 600 mutations have been fixed in one of the twelve lineages running in parallel. No two of them are the same today, even though they effectively started from the same clonal population.
Among them are every type of mutation. Duplications, deletions, insertions, transpositions, substitutions. Many of these mutations have happened in all sorts of genetic loci. In regulatory regions, in protein coding genes and what have you. They have happened in genes that affect regulation of cell division, in regions that affect DNA repair pathways, in transporter genes, in metabolic enzymes and so on. There is, evidently, an incredibly vast number of possible ways to further adapt the E coli cells to the flask environment and solve that problem, as each lineage has evolved along some unique mutational trajectory. Some of them have even mutated the same genes, but with different mutations yielding similar fitness gains.

The “problem” of being alive, metabolizing, dividing and reproducing for an E coli cell is a problem with an incredibly complex “solution”. And yet there keeps being new and different ways of contributing to solving that problem while increasing fitness, by genomic changes affecting basically every aspect of E coli molecular physiology.

In other words, vast numbers of other possible configurations of proteins corresponding to locomotive machines must be possible for any to be found. However, if so many possibilities exist, the chances of finding a solution which matches a human-designed outboard rotary motor so closely is nil.

That’s target thinking again. The chances of find any one of that vast number of solutions is nil, but chances are SOME solution will be found. And you can always sit back and try to calculate that after the fact that some complex solution was found, it was an incredibly rare solution out of that vast space. But all of the solutions will be. I’ve seen faces, humans, animals, plants, and even human designs in clouds. What were the odds that a could would come out with that particular shape that day and I would happen to look at it?

What use is that kind of after-the-fact calculation? What was the probability 25 years and 65.000 generations of E coli ago, that one of those 12 lineages of E coli would evolve those 600 particular mutations and find that particular ensemble of mutational solutions to increasing fitness? Having been given any imaginable list of 600 mutations we would have calculated something that would have looked nothing short of statistically impossible, but yet one of those combinations of 600 mutations did evolve.

What does it then accomplish to sit here now and try to work out how unlikely that combination of 600 mutations was? How how significant you happen to find how it looks to you?

However, if so few solutions exist in both the search space for human engineering and for biological systems that such similar designs appear in both engineering and biology, then the chances of nature stumbling upon one of them is nil, since functional combinations would be so rare. In summary, the fact that the flagellum matches so closely with a known design logic means that it can better be understood as a predefined target corresponding to a rotary motor than a haphazardly fit together collection of proteins which just happened to function as a motor.

That makes no sense at all. Anyone can find some personal or superficial significance in any imaginary outcome of the process. Some proteins look like bananas, others look like spaghetti, some look like fans, some look like sex toys. Was that intended too?

Natural selection cannot help add even a single piece to the motor, such as the filament, since adding the piece requires multiple highly-specialized proteins. Until all appear and are then fully integrated into the assembly process, natural selection would work against adding the filament.

When you call them “highly specialized”, you seem to assume without evidence that there is no possibility of functional crossover for a contingently expressed duplicate. As in they did not contribute to some other, more flagellum-related functoin until they fully crossed over in sequence space from one known homologue to another. How do you know that?

The production of a useless protein wastes resources and would be quickly disabled through mutations.

This is typical black-and-white, absolutist, creationist thinking. You see these things in two extremes between fully functional, or so deleterious as to be almost lethal.

It doesn’t have to be useless. And even if it was, there’s a very large crossover zone of lower and situational expression levels which can largely compensate for that, effectively rendering such a duplication invisible to selection, and slowing down the fixation of potentially inactivating mutations. The situation is simply not as black and white as you describe. There is a rather complex relationship between population size, efficiency of selection, and the fitness cost of gene expression. You just can’t make the kind of generalization you do here.

You might try to argue that each protein (filament, assembly cap, 2 joint proteins) served some other role, but the degree of specialization makes such a possibility difficult to justify. And, even if they did play some specific role in some other context, selection would prevent them from being redirected toward a completely different process.

Uhh, no it wouldn’t. Duplications into a region under control of a different promoter, compensatory epistasis, genetic drift, etc. etc. Did you read those two references I linked above? They deal with exactly a scenario such as you describe and what you’re saying just isn’t true.

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does it true for any function? say that we want to find a globin function. how many mutations we will need to find it in the sequence space?

what about human hand? dont you think that it resemble resemble a robotic hand for instance?

Robotic hands that resemble human hands were deliberately made by humans to resemble human hands.

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no problem. do you realy think that this doesnt resemble human designed? :

(image from arn.org)

That is an artist’s reconstruction drawn to look like a human produced motor. Here is the actual thing

At best it only superficially resembles something a human might design.

its are still very similar.

Big white cumulus clouds look very similar to fluffy bunny rabbits too. Science looks beyond superficial similarities.