Brian Miller: Co-option and Irreducible Complexity

That sounds like a Tu Quoque fallacy.

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But it isn’t one. And that makes all the difference in the world.

It is a Tu Quoque fallacy. You answered criticism with criticism without ever addressing the criticism.

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You should stick to science.

Red herring.

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No, that’s not an assumption made.

Rather, because the sequences of different but similar proteins exhibit significant levels of nesting hierarchical structure, that is actual evidence for common descent, because there’s no rational reason to expect that to be the case for a set of designed proteins even if they are all derived from some common template.

The key fact to consider here is that the more you try to “tailor” the design process to yield significant tree-like structure in the data, the more you have to effectively mimic common descent. Which makes the whole “design” aspect superfluous to requirements and irrelevant.

As a consequence, they compare the differences between different proteins or between the same protein in different taxa where the differences in sequences could be dramatic. They then assume that one protein could be gradually transformed into the other.

Well since the evidence before them literally implies that conclusion, they don’t so much “assume” it as they infer it. One has to wonder why one ended up with a data set that implies such transitions take place if the transition is supposed to be impossible.

We would not make that assumption since the two different proteins or the two versions of the same protein could represent separate isolated islands in sequence space.

Well, they could, but then why’d you end up with a data set that implies the opposite? Simply put, your interpretation is flat out less plausible, and seems to be motivated by no actual evidence other than misreadings of some papers you have referenced.

Instead, we focus on research which directly studies the limits of change or the actual rarity of functional sequences

But then you ignore their connections to other functions, or possible direct overlap. Axe only tested for one function, for example.

Another assumption of materialists is that observing any change generated by an evolutionary process, or at least an evolution-like process (e.g. abzyme research), justifies the claim that evolution could drive any change of any level of complexity.

Who makes that assumption, where?

This logic closely matches that of creationists who study how the flood waters from the Mount St. Hellen explosion generated layering patterns in sedimentary deposits. They argue that the capacity of a violent flood to produce those geological patterns justifies the belief that a massive flood could produce all geological patterns.

In what respect does the logic of those two match? It seems to me those two are wholly unlike, and I’m not saying that to defend the former. And please show who even thinks that “observing any change generated by an evolutionary process justifies the claim that evolution could drive any change of any level of complexity”? I’m calling straight up bullshit on that one.

No, they don’t. One of them (Bershtein et al 2006) was deliberately set up to exclude several well-characterized mechanisms of evolutionary change in order to better understand, in isolation, the consequences of a single mechanism of change in the absense of the effects of the others. It only allowed the effects of mutations within the reading frame of the protein. Potentially compensatory chromosomal mutations were avoided by deliberately only mutating the plasmid genes with PCR, and then transforming competent cells to measure the fitness effects of those mutations.

The TEM-1 gene was cloned into a plasmid (as it occurs in nature) under its endogenous promoter. Recloning after each round of mutagenesis confined the mutational drift to the open reading frame of TEM-1. Our in vitro random mutagenesis protocol was optimized for high reproducibility and was calibrated to obtain, on average, two mutations per gene per round of mutagenesis. We maintained three populations of randomly drifting TEM-1 genes: one population under no selection (Lib0), and the rest under purifying selection at ‘high’ and ‘low’ stringencies. Each population, or plasmid library, was separately mutated, ligated into an empty vector and transformed into E. coli host cells; it then underwent purifying selection: ‘high’ selection pressure (250 mg ml21 ampicillin; Lib250; Supplementary Fig. 2), and ‘low’ selection pressure (12.5 mg ml21 ampicillin; Lib12.5). After growth on selection plates, plasmid DNA was extracted from the surviving E. coli colonies, and the TEM-1 genes were subjected to the next round of mutagenesis. Altogether, ten successive rounds of mutagenesis and purifying selection were performed. Loss of diversity was less than 50% per round, and a diversity of at least 10^6 variants per library was maintained throughout.
As expected, a rapid fitness decline was observed in Lib0 (no selection). The fitness of the selected populations (Lib12.5 and Lib250) remained unchanged under the threshold of selection, and decreased above that threshold (Supplementary Fig. 3).

This completely rules out the possibility of compensatory duplications, other forms of regulation of gene dosage, compensatory chromosomal mutations, and so on.

And even then, it is noteworthy that the aspect of the protocol that involved purifying selection was still able to maintain structural integrity of the protein against the prevalence of deleterious mutations.

Fig. 3. The fitness ‘landscape’ of the TEM-1 gene.
The fitness dynamics of the different TEM-1 libraries is presented as a function of mutational input. The average fitness (W) of a given population was defined as the fraction of β-lactamase variants that confer resistance at a given concentration of ampicillin (see Methods). Wild-type TEM-1 exhibited W=1 for all ampicillin concentrations ≤ 2500 µg/ml. All fitness measurements are detailed in Supplementary Table 1.The rapid fitness decline of the unselected library Lib0 is shown at 12.5 μg/ml of ampicillin (○). The fitness of the libraries subjected to purifying selection remained unchanged at concentrations under the applied selection thresholds, as exemplified here by Lib12.5 at 50 μg/ml ampicillin (∆), and Lib250 at 500 μg/ml (F). At concentrations exceeding the selection thresholds, constant decreases in fitness were observed, exemplified by Lib12.5 at 500 μg/ml ampicillin (◊). Note that the impact of ampicillin is much higher on freshly transformed cells (as in the purifying selections) than on ongrowing, replicated colonies (as in the fitness measurements). Thus, the threshold ampicillin concentration for the fitness measurements was found to be ≤100μg/ml for Lib12.5 (selected with freshly transformed cells at 12.5 μg/ml ampicillin), and ≤1000 μg/ml for Lib250 (selected at 250 μg/ml).

The other paper you cited (Lundin et al 2018) explored the fitness effects of mutations and found, completely unsurprisingly that most mutations are deleterious. They didn’t find anything which supports the view that protein evolution can only go downhill as mutations accumulate. Their protocol did not even include a lineage evolving under purifying selection. All mutations were created directly in DNA by PCR and then inserted in the bacterial chromosome and their fitness effects were tested. When the effects of multiple mutations in combination were tested, it was again the in absence of purifying selection.

The structural and sequence differences between flagellar proteins and their hypothetical closest common ancestors are so great that the evolution of the former involves a far different protein sequence entering the vast sea of nonfunctional sequences

How do you know that? Please show the experiment that shows this.

The cited experiments demonstrate that the negative impact of mutations and the percentage of harmful mutations increase with the number of accumulated mutations.

In the deliberately designed absence of purifying selection, compensatory epistasis, and variable gene dosage effects.

Thus they DON’T mirror “evolution in reverse”, and drawing conclusion from them about what the limitations of real protein evolution is actually like is logically fallacious.

Note that I am not focusing on what the authors imagine could be true but on what their hard data demonstrates to be true.

Note that I’m not focusing on what you imagine could be true, but on how the actual experimental conditions were set up to.

The authors discuss how compensatory mutations and buffering effects (e.g. chaperones) could increase the threshold before accumulating mutations destabilize the protein. For instance, the negative effect of one mutation could be undone to some extent by the following one, so the sequence might change significantly more than average with a less negative effect

Yeah, that’s what happens in the absence of purifying selection. If deleterious mutations aren’t weeded out, they invariably accumulate. If no compensatory effects are allowed, fitness will decline. This is a surprise to exactly no evolutionary biologist ever.

However, such series of mutations maintaining significant fitness would represent a very narrow corridor in sequence space as judged by the dominance of harmful mutations over compensatory ones. In general, compensatory mutations and buffering increase the threshold for stability by only a limited amount. After a certain number of mutations, the limit is reached, and the protein quickly loses function with most new mutations. After about 10 mutations in B-lactamase and HisA, the majority of the following mutations are lethal. After several more mutations, nearly every subsequent mutation is lethal.

Which is why purifying selection matters.

These results are from actual bacteria, so they take into account any buffering effects.

No, they don’t. You didn’t read, or didn’t understand the methods sections. The protocols were specifically designed to EXCLUSIVELY test the effects of mutation accumulation on the protein coding gene on organismal fitness or protein stability in the ABSENCE of other chromosomal mutations.

In one lineage in the first study, the organisms were NOT allowed to evolve under selection. The plasmid carrying the gene of interest was transformed into the bacteria, and their fitness was then measured. Then the plasmid was purified from the bacteria, mutated some more, then transformed back in again into newly thawed clones chromosomally identical to the previous population. In THAT lineage, fitness declined, as selection was explicitly prevented.

In two other lineages where stronger purifying selection was allowed, fitness did not decline. Yet the proteins still accumulated lots of mutations.

In the second paper you reference there was no purifying selection allowed at all.

The authors argue that the destabilizing trend is a general property of proteins.

Which it is in the absence of purifying selection.

As a consequence, the rarity of proteins in the region around any functional sequence is so great that no functional protein could ever be found. For instance, the B-lactamase studies indicate that after about 5 non-synonymous mutations, around 1 in 3 amino acids could be tolerated at each site, so the rarity is almost identical to Doug Axe’s results. The HisA results are even worse. After around 10% of the sequences change for either protein, all functionality, based on their numerical fitting, is permanently lost. These regions are completely devoid of functional sequences. As a consequence, most of sequence space is so sparsely populated with functional sequences that no search could ever find any protein in the entire history of the earth.

For reasons already discussed this conclusion is highly doubtful, and simply can’t be extracted from any of the experiments you cited. You’ve failed to understand the methods sections of the papers and thus you don’t seem to understand their limitations. Heck, you don’t even seem to have really read all their results, as both papers experimentally demonstrate the sufficient efficacy of several compensatory and buffering mechanisms, such as purifying selection and gene dosage effects.

Amazing.
Edit: This post has been edited to correct some spelling and grammatical mistakes.

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I should point out that most of your audience lacks the attention span of German-born Physics majors, working on a double-major in Chinese translation of Tibetan theology.

Generally, one does better with 2 or 3 shorter postings than with one massive Tome!

To summarize, @bjmiller claimed in his essay that
All evidence points to the conclusion that the formation of the flagellum requires vast quantities of new genetic information…”

This is false. Brian Miller even implicitly admitted that he was unfamiliar with a vast amount of the relevant evidence.

@Rumraket and others are pointing out that the tiny number of studies cited by @bjmiller don’t support his claims either.

The most ludicrous claim is this one:

Brian Miller has yet to explain why experiments that allegedly “resemble evolutionary narratives running in reverse” are more informative than the much larger number of experiments that model evolution searching forward, the natural direction.

There’s also the elephant in the room of the body of evidence we have from directly looking at nature’s evolutionary narratives going forward, as in natural variations, which don’t support Brian Miller’s claims either.

I could describe that for a particular set of inherited diseases if there is interest.

The natural direction im running in is that im dying. The natural direction that the universe is running is that it is also dying.

Ah, the good old 2LoT argument.

While you are “dying” do your hair and fingernails keep growing? How can that be if everything always degrades all the time??

I bet you’re not aware there are known natural processes which locally decrease entropy (i.e. produce more complex components from simpler components and energy) as long as the overall system entropy still increases? They’re called endothermic chemical reactions. Photosynthesis is probably the most well known of these type of reactions.

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I would say that @scd just proved abiogenesis by turning an inanimate fadhion piece into a biological organism.

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I agree that general laws of entropy is not a perfect argument against neo darwinian evolutionism. It still is interesting to wonder if theres pattern in the cosmos created by a great Cause that translates in a parallel way in our solar system. God created the cosmos…bodies of mass energy in stars and planets and it is running down. Could the same be said of creation on earth where bodies called “kinds” are also running down?

The nature of the average mutation however that supposedly become accumulated and selected does not at all paint a picture of evolution to complexity but rather devolution from complexity to simplicity towards extinction. The second principle that i find interesting is that generic selection we call breeding in the dog species results in genetic loss. This means that the breeding that mimics selection, in time makes that dog lessor capable of survival. Isnt this the big picture that Behe engages more detailed scientific principle to confirm?

These are two big evolutionary deal breakers…and they happen to match the very principles found in the cosmos where mass energy becomes disorganized. To me, i becomed pretty humbled with this. I think, “So i believe in God, and now it seems that i can actually see His very fingerprints in the natural world.”

No Greg, it doesn’t. That’s your scientific ignorance talking again. Evolution works by modifying existing structures. Sometimes that means becoming more complex, sometimes that means less complex. It depends on the selection pressure of the particular environment which is usually always changing. Behe’s claim everything "devolves"or “breaks” is just idiotic word smithing.

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Well then, you are starting to prove that the theory of evolution true to me sir. there was a seed of thought planted called darwinian evolution that rode in the back of natural selection. But this was not quite right. So this thinking evolved to neo darwinian evolution that supposes that genetic mutations were the key ingredients that natural selection chose from. But the rational ones out there thought to themselves,"eyes, eye muscles, eye sockets, nerves and brains could not possibly have been built from damaged construction materials called mutated genes… So now science has fully evolved as Tim Horton has given us the ultimate truth we might call the neo neo darwinian theory of evolution:“Evolution works by modifying existing structures.”
You have proven evolution to be true and thankyou for the illumination.
Please dont interpret my satire as unlovingness. I care for you Tim Horton. God cares for you more You are on my prayer list.

I have grown to observe that this debate is far more philosophical and far less scientific than you and many others here would want to acknowledge.

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Only from your end, and that’s because you are completely clueless on the science.

I agree the second law gets abused more often than it should…but it also gets dismissed more often than it should. It is possible that this will be review for most, but the current thread makes me think not for all.

The basis of the second law is the concept of multiplicity. Let’s think about a warm cup of coffee cup sitting on the counter away from any heat source. Since the air in the room is cooler (meaning less energetic on average) than the coffee, each random interaction has a much better chance of pairing a less energetic air molecule with a more energetic coffee molecule that it does of pairing a more energetic air molecule with a less energetic coffee molecule…so the coffee cools.

In most cases, there is enough energy in the room to heat the coffee, so it is not impossible that the coffee could warm randomly…there is no physical law that prevents it. However, if we had a way to examine every possible interaction in the system we would find there are MANY more interactions that would cool the coffee than there are interactions that would heat it. The law of large numbers acting on the imbalance in the probabilities almost guarantees that if the interactions are left to chance the coffee will cool.

In the case if hair and fingernails, the physiology of a living human body actually reverses the inherent probabilities between growth and decay. If the body is working correctly, the chances of hair and fingernail growth is a near certainty, but that does not mean that the second law is suspended…it just means there is work being done to overcome the normal probability imbalance that greatly favors disorder. Photosynthesis is similar…cell has information and hardware that is capable of doing the work necessary to keep the probabilities balanced in the plant’s favor.

Eventually the systems ability to do that work will cease (due do a lack of energy input or some decay in the system itself) and the balance will return to favor decay. We can be assured it will happen just because there are always more ways for random interactions to introduce disorder into a a system than there for random interactions to introduce more order.

The most common dismissal of the second law is the compensation argument…that the loss of order in the sun more than offsets the gains seen throughout evolutionary history…is too often uncritically accepted. The disorder increasing in the sun is essential as an energy source…but the raw energy and heat it provides to the system is not sufficient in itself to balance the probabilities involved in evolutionary scenarios. For order to win, something has to do the real work of bringing the probabilities involved more into balance.

Since there is positive evidence in many scientific disciplines that evolution has occurred, we have scientific reasons to think that the whole of the evolutionary process is capable of balancing the probabilities. At the same time I think it is fair to say that people who believe that evolution has occurred usually are convinced more by that positive evidence than they are by a thorough analysis of the multiplicity involved in how the various probabilities balance.

Personally, I don’t believe selection alone working on truly random (meaning unguided in some way…natural or supernatural) is enough to overcome the probability imbalance that most everyone admits exists…even if they argue endlessly about the degree of the imbalance. I come from a background in physics and information systems design, so I understand the complexity involved in building information processing systems (or any physical systems for that matter) that function well…and I have very little fear that an evolutionary software design system will someday take my job.

Random changes can and will move the system toward order some percentage of the time, but if any significant imbalance exists between the probability of advance and the probability of decline, the multiplicity of the system will result in a net decrease in order over time.

If evolution works…and like I already said…there is a large amount of positive scientific evidence that it does (so be kind :-))…it is because SOMETHING is causing the individual mutation events to move toward order (in the form of fitness for the environment) at least slightly more often than they move toward disorder…or the process would be powerless to resist the law of large numbers acting on the fact that each truly random unguided change has a MUCH better chance of breaking something than it does of building something.

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And yet you can still produce offspring.

The natural direction that systems run towards is an increase in order when there is energy dumped into them. Have you ever heard of this gigantic fireball that is pumping energy into Earth’s systems? Yeah, it increases order on Earth. For example, our oceans are very ordered with a strong temperature gradient between the poles and the equator. According to you, this shouldn’t exist.

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Once you have imperfect replicators competing for limited resources, evolution is all but assured. Thermodynamics is already taken care of at the level of the organism, specifically in the biochemical pathways that drive thermodynamically unfavorable reactions.

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It’s called natural selection, part of the overall process of evolution. Because of the feedback provided by selection beneficial mutations tend to accumulate, deleterious ones tend to get weeded out. That feedback loop moves populations towards reproductive fitness local maxima i.e. more ordered with greater chance to reproduce.

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