Brian Miller: Co-option and Irreducible Complexity

You are assuming that what did evolve is the only thing that could evolve.


No, that would be a silly thing to assume. more so in light of the fact that I’ve stressed that it would be no different if it were two different proteins that had evolved to perform two separate functions. It was T.j.Runyon who was stressing that they perform the same function, as if it was the only function that could have evolved.

How many proteins that could have evolved didn’t evolve?


Yes. On one level, you’re assuming that you know it all, but on another, you know that you know very little.

The “ID analysis” avoids both advancing and testing scientific hypotheses. It is classical pseudoscience.

The real scientists are always formulating and testing hypotheses.

That is illustrated above in the following exchange:

You did not respond. Do you see a testable hypothesis there, or does your job description not allow you to look for testable hypotheses?

No one knows how many proteins could have evolved.

Then you don’t know what the target sequences are.



It’s not clear to me that you are actually following the discussion. You just seem to be firing off a string of comments without concern about whether they make any coherent sense as a whole. What is your argument?

My argument is that you have to know all possible functional sequences before you can make any claims about the probability of evolution finding function.

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That sounds suspiciously like the claim that you have to know all the details of how the flagellum evolved before you can claim that it did.

Science and in fact life in general manages to proceed just fine without us knowing all the possibilities (or all the details) before making a judgment or inference. What you are doing is engaging in special pleading. A fallacy.

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.


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.

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


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.


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