It has been widely advertised that nylon eating genes evolved after 1940. I have no problem with that claim in principle since new antibiotic and malaria resistances have evolved since 1940. Even though I can easily accept the possibility of post-1940 nylon-eating evolution in principle, where is the slam dunk evidence that this is actually the case? Did a significant portion of the ability for bacteria to digest nylon take place after 1940 (or 1935 when nylon was first created)?
In an NCSE article New Proteins Without God’s Help we read:
Since nylon first came into commercial production in 1940, we know that the new enzymes have formed since that time.
A similar line of thinking was argued at BioLogos in Biological Information and Intelligent Design, De Novo or Ex Nihilo.
Three nylon eating genes NylA, NylB, NylC were discovered on the Flavobacteria plasmid pOAD2 from 1977-1992, but the researchers concede none of the three have significant sequence homology. Worse, in papers published in 2007, they reported other bacteria contain those same genes in their chromosomes. Unless the researchers have access to pre-1935 bacteria sitting in lab refrigerators, the claim that the genes actually evolved new proteins via mutation is dubious since we have no pre-1935 bacterial samples to actually do a comparison with, especially in the case of NylC. The claim that NylB’s nylon eating ability evolved by gene duplication from a non-functional NylB-prime gene could just as well be interpreted that a functionless NylB-prime gene is a defective copy of a functioning NylB gene!
What’s the proof new nylon eating genes actually evolved after 1940, or is it just speculation? Slam dunk proof would entail having strains of pre-1935 bacteria and then comparing it with the strains after 1935 that supposedly evolved new genes. Is that the case? No. Just speculation which began in 1977 but got less defensible over the next 40 years as more bacteria and non-sequence-homologous genes were discovered to have nylon eating capability.
At least we can credit Richard Lenski who can back up his claims of evolution because he has samples of bacteria in his lab before and after his creatures evolved, whereas the guys promoting the claim the nylon-eaters are new don’t have pre-1935 physical samples of the bacteria. The only pre-1935 samples of the bacteria they have are samples from their imagination.
Incidentally, it is worth pointing out the bacteria that is the centerpiece of the controversy has been mis-classified or misidentified, and thus the name of the bacteria has itself gone through some sort of macro evolution. It was first called Acromobacter gattatus, then renamed as Flavobacterium sp., but then renamed Arthrobacter sp. after it was realized it had been put in the wrong taxonomic category all along.
But anyway, here is the 1977 speculation that became uncritically accepted and exaggerated as fact for the last 40 years:
There are two possible mechanisms for an enzyme to be active towards unnatural synthetic substance such as 6-aminohexanoic acid cyclic dimer; one is that an unnatural compound is hydrolyzed as an analogue of the physiological substrate, and the other is that the compound is hydrolyzed by an evolved enzyme which originally had an activity on a physiological substrate but lost it by the evolutionary mutation. The data obtained in this experiment indicate that this enzyme did not hydrolyze any physiological substrates tested including peptides, cyclic amides, and amides. In addition to the lack of activity on natural compounds, its low turnover number (8 SKcI) compared to other cyclic amide hydrolases (35 – 260 s ~ for penicillinase [12]) supports the possibility that the enzyme has evolved by adaptation to a new synthetic substance which is a waste product of nylon-6 production.
I have no problem if they say “the enzyme has evolved by adaptation to a new synthetic substance which is a waste product of nylon-6 production” when they mean an existing enzyme has changed its pre-existing function to a different one. That is to say, it acquires a new function while also losing its previous one. However, I would have serious issue with the NCSE’s insinuation that this was such a spectacular change that it illustrates how to solve the origin things on the order of the spliceosome or ribosome.
They don’t have strains sitting in a refrigerator from which to compare the “newly evolved” genes with do they? They just guessed, and then 30 years later one of the same team (Negoro) found nylon eating genes on other bacteria, plus reasonable nylon-eating homologues on other bacteria to boot.
Worse, the claim that these are post-1935 genes is weakened by some facts that require a little elaboration. First there is the basic nylon monomer that forms the components of nylon oligomers. NylA, NylB, NylC have different specialties of which nylon oligomer they can degrade. These three enzymes provide what looks like a digestive cascade where N-oligomer substrates are degraded by NylC to dimers which can be further degraded by NylB (and even NylC but to lesser extent). The cascade is described in: Biodegradation of nylon oligomers.
But important to note: NylA, NylB, NylC are not sequence homologous. In A New Nylon Oligomer Degradation Gene (nylC) on Plasmid pOAD2 from a Flavobactenium sp we read:
Sequence alignment by the method of Wirbur and Lipman (21) showed no significant homology among the
nylA, nylB, and nylC genes. These results suggest that the three nylon oligomer-degradative enzymes evolved independently.
There is no pre-1935 bacteria from which to compare with to establish NylC’s true history, much less anything beyond speculation about the nature of NylC’s ancestor. So how can anyone claim it is new (as in post-1935-new)? Just guesses. They’d have to argue these the genes evolved independently since 1935, and in the case of NylC, the ancestor is almost totally without detailed description.
They however argue, a functional NylB arose from a non-functioning NylB-prime gene via gene duplication in a 1991 paper entitled: Evolutionary adaptation of plasmid-encoded enzymes for degrading nylon oligomers.
But for all we know NylB’ is a defective copy of a functioning NylB! Where is a Ken-Miller-pseudo-gene-like argument when you need it?
In fairness, another bacteria called Pseudomonas was shown in lab conditions to acquire enzymatic nylon-eating function after a few months. The gene however in Pseudomonas, according to BLASTN, has no sequence homology with Flavobacteria. However, the protein according to BLASTP can align 91% at 37% homology. But even the researchers were astonishingly vague about what actually changed in the bacteria that enabled nylon degredation. The two relevant papers are: Characterization of the 6-aminohexanoate-dimer hydrolase from Pseudomonas sp. NK87 and Emergence of Nylon Oligomer Degradation Enzymes in Pseudomonas aeruginosa PAO through Experimental Evolution.
Unless we have strains sitting in a refrigerator of pre-1935 bacteria, how do we know that the genes actually evolved to digest bacteria? For all we know, it had that capability already or very close to it. And unless we have genes from all existing bacteria in 1935 and can prove all the bacteria on the globe do not have horizontally-transferrable nylon eating genes which could end up on the plasmids of Flavobacteria, we can’t unequivocally argue the three nylon eating genes (NylA, NylB, NylC) in Flavobacteria didn’t already exist pre-1935.
Even if the capability of nylon eating evolved, it is also not necessarily because of a new gene, but new regulation. A mini-example of this possibility had to be raised because even in their lab, they had bacteria with identical nylon eating genes but which could not digest nylon.
it is conceivable that expression of the nylC gene is enhanced in these strains and the elevated enzyme activities made the cells Nom+. However, the following possibilities could not be ignored: (i) KI725R strains may possess an additional nylon oligomer-degrading enzyme which is active
toward a substrate included in Noml, but K1725 has no degradative ability toward the substrate; (ii) nylon oligomer transport proteins are activated in K1725R strains; or (iii) the EIII proteins were altered by mutations in the coding region of the nylC gene by which the specific activities and/or
substrate specificity of the enzyme were changed. The last possibility should be negligible,
So my question is, if we ignore the NCSE hype, does the scientific literature really even prove unequivocally a significant part of nylon eating genes evolved after 1935 and absolutely rule out these genes pre-existed? Maybe yes, maybe no, but the NCSE can’t now brag that any significant evolution (like say compared to evolution of antibiotic resistance) bacteria definitely evolved after 1940 without God’s help. We simply don’t know.
NOTES:
Here are some accession numbers:
NylB (protein) in Flavobacteria: WP_012476894.1
which generates a BLASTP hit on Agromyces accession number: BAE97621.1
NylC (protein) in Flavobacteria: BAA01528
which generates a BLASTP hit also on Agromyces accession number: BAE97629.1
in Pseudomonas, the nylon eating gene accession numbers are : BAA01524 (protein), D10678.1 (DNA)
which generates BLAST hits on a variety of organisms as well
There is no anti-ID argument that says new functional proteins must be created by frameshift mutation “all the time”. None of these claims are necessary aspects of any anti-ID argument.
The ID argument is that these events are so rare as to not even possibly happen even once. That’s what Ann Gauger basically concludes in her long post full of misinformation and irrelevancies.
As she writes: “What Doug Axe, Stephen Meyer, and I say is that the probability of the appearance of de novo functional protein folds by random association of amino acids is practically zero.”
She quotes François Jacob 1977 in support of this statement. Notice that no reference is given when François Jacob says it. So when it is shown to have happened even once, then that ID argument is just plain wrong.
lol
Something I’d really like to investigate is the nucleotide sequence from the plasmid pNAD6 from the bacterium Pseudomonas aeruginosa strain NK87. This pNAD6 plasmid is the one that carries the P-NylB enzyme that is ~37% similar in amino acid sequence to the F-NylB/F-NylB’ enzymes.
But I have not been able to find the nucleotide sequence for that plasmid in any database. I would particularly like to look at the upstream to P-NylB region of that plasmid, to see if it shows any indication of having once exhibited a coding region that is similar to the one upstream of the F-NylBs.
I am intrigued by the fact that this upstream region is so well conserved between the F-NylB and F-NylB’ on the pOAD2 plasmid and I wonder why that is. Does it have to do with transcription factor binding?
Why are you asking WHY if you believe in evolution?
There is no why, it was an accident that didn’t have a negative affect.
I would think it obvious I was wondering about the cause(s) of conservation of that sequence. Not that I believe there is any intent behind it. But even if we suppose thete is, it is a fact to be explained regardless of whether it evolved or was designed. How did it come to be there?
There are several different possibilities here from the evolutionary perspective, but to determine which one is correct I need more data. The kind of data that could help indicate this is in the flanking regions of the NylB genes on different plasmids.
Nobody has even bothered trying to explain it using design. I submit there is no sensible design hypothesis for it.
Just because something is extremely improbable it doesn’t mean it’s impossible. And just because something happens once, it doesn’t go from being extremely improbable to being likely. DarwinLogic fails.
You can’t refute Axe’s figure from a sample of one. Try again.
I’ve never argued that frameshift mutations creating functional proteins are “likely”, whatever that even means.
Reading comprehension fail.
Clearly Ann Gauger thinks that this frameshift mutation, if it happened, is a problem for Axe’s and her own claims, which is why she tries to undermine it.
As she wrote:
“Now, here’s where I come in. It seemed highly unlikely to me that a stable, functional protein fold could arise by frameshift mutation, unless the sequence was designed that way. Among geneticists frameshift mutations are called “nonsense” mutations because they typically result in scrambled non-functional code. In fact, this view of frameshift mutations was pretty universal until we began to encounter what looked like frameshifts in sequenced genomes.”
She also wrote back in May: “Their claim is based on the experimental finding by Doug Axe that functional protein folds are exceedingly rare, on the order on 1 in 10 to the 77th power, meaning that all the creatures of the Earth searching for the age of the Earth by random mutation could not find even one medium-size protein fold.“
Not even one.
She also writes: “Venema is right. If the nylonase enzyme did evolve from a frameshifted protein, it would genuinely be a demonstration that new proteins are easy to evolve. It would be proof positive that intelligent design advocates are wrong, that it’s not hard to get a new protein from random sequence. “
So Ann Gauger disagrees with you Mung. And Sal appears to agree with her, which is why he tries to undermine it too.
But you’re clearly confused about what I’m trying to achieve with this particular argument Sal and I are having. I am not trying to imply that because there was this single frameshift mutation, therefore they are “likely” to happen (in this I actually agree with you, that doesn’t follow and Ann Gauger is clearly arguing fallaciously). I am only arguing that when Sal claims there’s no evidence that it happened, that he is wrong about that.
And I am arguing that Sal is stuck between a rock and a hard place, because either he accepts that the frameshift mutation happened and created a new functional gene by chance, or he denies it happens but then is forced to accept that by chance the bracketing and overlapping reading frames just so happens to produce a protein that folds like this:
That’s why I wrote a separate OP wherein I cite multiple experiments all of which refute it.
Try again squire.
Wasn’t it supposed to depend on how improbable it is?
https://en.wikipedia.org/wiki/Universal_probability_bound
Rumraket,
How does an experiment refute something that has different conditions then the ones you cited?
The op was valuable but what you showed is that the abundance of protein folding and function in sequence space is variable depending on the function (s) being preformed. This confirmed Art Hunts prior thesis.
If you want to challenge Axe’s experiment then set up the same conditions.
Read my fucking op Bill. The problem isn’t with the experiment per se, it’s with the interpretation of it that Axe and others then go on to give to people who don’t have the qualifications to assess his work. That Axe and the people over on EN&V are spinning his results to apply to all of 150 aa protein sequence space for all possible functions.
They wrote: “This paper is interesting because it relates to the work of Douglas Axe that resulted in a paper in the Journal of Molecular Biology in 2004. Axe answered questions about this paper earlier this year, and also mentioned it in his recent book Undeniable (p. 54). In the paper, Axe estimated the prevalence of sequences that could fold into a functional shape by random combinations. It was already known that the functional space was a small fraction of sequence space, but Axe put a number on it based on his experience with random changes to an enzyme. He estimated that one in 10^74 sequences of 150 amino acids could fold and thereby perform some function — any function.“
The claim made about what Axe’s experiment shows has been completely and utterly refuted.
And we have a 427 AA long protein here, don’t we? Not just 150, a whooping 427 long sequence! Since Bill keeps claiming that the longer the sequence, the more improbable it is to find function in it, how does Bill explain this?
Lulz
True, but to be fair we don’t actually know whether that 427 aa sequence is still functional. If it really is a remnant of the age indicated by the divergence of F-NylB and P-NylB, chances are it isn’t.
That’s completely and utterly false.
OK, so the novel protein is obviously not Ohno’s proposed relic, of course.
So according to Venema the new protein is 392 AA’s long, if I got it right.
Now, I haven’t seen an actual argument or evidence to support the function density is lower as the squence gets larger, but perhaps Bill can shed some light on it
Have you run the math?
No, it isn’t. It’s a fact and if you believe otherwise, you’re proving to me you’re not qualified to even discuss it.
The matter is COMPLETELY settled.
Is there an estimate of the average amount of time that it would take to find some function if Axe’s figure was right?
There isn’t any reliable one as far as I’m aware. When Ann Gauger says not even a single one could have evolved in the history of life on Earth, she doesn’t perform any calculations to show this, she just pulls that estimate out of her ass.
Regardless, even if you could do such a calculation it wouldn’t show much, because what probably matters more than the average density of function in protein sequence space, is the interconnectedness of the functions in that space, and the means by which movement in that space can take place.
If movement around in that space is restricted simply to point mutations, then the diversity of functional proteins we see probably could not have evolved. But if mechanisms like exon shuffling, varying size insertions, inversions, deletions and gene fusions are included (all of that stuff known as gene-duplication and recombination), there has been work done which shows that it can. I’m not qualified to assess their math, and their work is mostly math.
I don’t know but I don’t even think that such a number would tell us much. After all, it could be the case that the average number of mutations to convert one protein to the function of another was rather large, but that the majority of protein evolution happened by tinkering around with functions that already exist at very low levels, and that most novel functions are created de novo by non-coding DNA or, again, exon shuffling, recombination and so on.
There are examples of total functional conversions of proteins by single mutations, though. And I mean total conversion, where a protein that used to function like an guanylate kinase enzyme and catalyze the chemical conversion of some substrate, instead became a structural element that binds different cellular components together. And that radical shift in function was caused by a single amino acid substitution. See Evolution of an ancient protein function involved in organized multicellularity in animals.
Rumraket:
Mung:
Mung,
For our entertainment, why not present your counterargument?
Looks like links keep getting lost somehow.
This should work: The Time Scale of Evolutionary Innovation.
Krishnendu Chatterjee , Andreas Pavlogiannis, Ben Adlam, Martin A. Nowak
https://doi.org/10.1371/journal.pcbi.1003818
LoL. Did you even read that?
And why aren’t you over in Tom’s thread telling him how wrong he is, assuming you actually believe what you just posted?
You realize that by target they’re just talking about any arbitrary sequence of a specific length, not some specific target? Like, how long does it take on average for [a 1000 nucleotide gene] to evolve. That’s the kind of work they do. Their targets are just sequences of length L. It doesn’t really matter what that target really is.
Did you read it? I suggest you proceed to the introduction, now that you’ve read the abstract.
Rumraket,
I find interacting with Mung to be uniformly useless. Why do you bother?
Mung is remarkably dim. On the Evo Info 3 thread, he’s revealed that he still doesn’t understand how Weasel exposes Hoyle’s fallacy.
What is the cause of no accidents to that sequence? That’s the question?
Rumraket:
phoodoo:
Phoodoo is battling it out with Mung and colewd for the title of “dumbest evolution critic at TSZ”.
And they’re all so deserving…
Glen Davidson
John doesn’t even try to interact with me, he has me on ignore. That was his way of responding to someone who dared challenge his Darwinian storytelling.
John’s lack of imagination when it comes to all the possible stories that might be told as to why birds have an ovary that doesn’t function ought to have resulted in his losing his Skeptic badge.
You were the one that posted the abstract. Now you say the abstract contains lies?
That’s what you say. Here’s what they say:
So they lied?
I don’t believe you. The length is simply a variable.
Here it is for you:
#SnowJob
There are alternate explanations
But none that John could think of.
No, all of that confirms what I said. They merely re-stated the same thing in other words. It’s still exactly what I described. No actual real functions are considered as targets. It’s still just arbitrary sequences of some length.
Also, it seems you’ve moved away from talking about Axe and Gauger’s work. I know why. It’s because it’s bullshit, and with the quotes from Gauger I gave, you now realize she’s a bullshitter. They both are bullshitters.
Maybe you should do a post on the possible explanations.
So? He has the common sense to not interact with obvious trolling assholes.
Regarding protein folding, there are native and non-native folds.
https://en.wikipedia.org/wiki/Native_state
The fact that prions exist shows that native folds don’t necessarily imply which way a protein will actually be folded in a biological organism.
The Levanthal Paradox deals with native folds, not other possible folds.
That’s why I wasn’t particularly impressed with the folding diagrams Rumraket posted. The protein folding problem often deals with the native fold, it doesn’t mean the protein can’t fold a buzzillion other ways. Hence it’s easy to force a fold alignment.
How does Rumraket know that alignment doesn’t denature Ohno’s PR.C protein with the typo in it? And that is generously assuming there is a functional native fold to begin with that is biologically relevant to the organism.
By biologically relevant I mean of functional utility to the organism. We genetically engineer yeast and bacteria with human insulin for diabetes research and treatment. Functional human Insulin doesn’t do much good for bacteria and yeast.
Rumraket,
How familiar are you with I-TASSER? How did you come across it? This was my first encounter with it, and my academic background is in physics, I’m naturally inclined to like discussions about 3-D structures. Thanks for introducing it to me.
I don’t think the alignment to another protein is forced. From what I understand about how the I-TASSER service works, many thousands of folds are generated for the sequence, and then some number of these folds will “cluster” around each other due to their overall similarity. From these clusters, a representative model is then picked and compared against the database of structures.
All of these are interesting points in themselves, and obviously I can’t really answer them. The most realistic test of folding would be to make the PR.C protein in the lab, get it biosynthesized and it’s structure analyzed if possible. But that’s just not a position I’m in where I can do that. For this discussion, all we can do is work with publicly available tools on the internet.
I will say that a big disadvantage here is the low level of sequence similarity to all the proteins that have resolved structures. I wrote an expert in protein structural phylogenetics but I haven’t heard anything back. Ultimately for my own peace of mind I’d like someone who is familiar with this kind of work to look it over. I’ll probably write someone else this weekend.
I don’t do any work like this professionally, so my familiarity with it I readily admit is superficial at best. I have been wondering about the fold prediction method employed by the server myself and whether it can really be trusted.
Annoyingly, as far as I could gather none of the several hundred proteins to which the PR.C scores significant sequence-alignments, have resolved structures. This leaves us in the unenviable position of only having these kinds of software tools to work with.
Thank you nonetheless for introducing me to I-TASSER. Sorry we have to disagree on so many matters, but with respect to I-TASSER, I’m indebted to you.
Ironically, one of the things I pointed out supports a point you made about enzyme function, namely and protein might theoretically be able to catalyze some unknown reaction.
For example, trypsin is a protease. That means it cleaves proteins. Lipase is a lipase, it cleaves fats. Both of these (trypisin and Lipex50T lipase) cleave nylons.
So that supports one of your criticisms of creationists and improbability of protein function. A given protein could hypothetically be a catalyst for some enzymatic reaction somewhere.
That said, the reason I cited Trypsin and LIpex50T (if I had not already mention Lipex50T) is that it lends credence to the hypothesis NylB and other nylonases actually had biological function pre-1935.
If NylB couldn’t cleave the biological compounds Kinoshita tested it on, it means he either wasn’t testing the right reaction or that NylB, in the process of acquiring nylon cleaving ability, lost its ability to process biological substances. If evolution happened, I think a few post-1935 point mutations within the framework of Luria and Dellbruck did the trick.
Ohno thought Okada invoking gene duplication followed by 40 residue mutations was not possible in the timeframe after 1935, hence he offered up his post-1935 frame shift as an alternative. It think, however, if Kato’s 1991 2-residue experiment on NylB’ that conferred nylonase ability had been available to Ohno, I think Ohno might not have published his hypothesis since there would have been no need at that point. A 2-residue, not a 40-residue mutation was all that was needed in principle. Added to that, we still don’t know if there was any need for nylonase adaptation in the first place since nylonases are ubiquitious, albeit only few organisms have been shown to be capable of actually living off nylon exclusively.
In fact, if a human digested nylon and his nylonases cleaved the nylon, the cleaved monomers, namely amino caproic acid, would be toxic. I know this because the US FDA has labeled amino caproic acid as a prescription drug with potentially toxic effects.
How the bacteria are able to digest amino caproic acid is yet another mystery. Nylonase is a necessary but not sufficient condition for being able to live off nylon.