Nylonase: Move On, Nothing to See Here, Says Theistic Evolutionist
The supposed sudden emergence of the enzyme nylonase has been a chief talking point for the power of evolution for many years, and it has made its appearance multiple times in Dennis Venema’s series of posts, “Letters to the Duchess,” at the theistic evolutionist website BioLogos. Here’s how Venema, Fellow of Biology, described it in a post last year:
Intelligent Design and Nylon-eating Bacteria
[Nylonase] arose from scratch as an insertion mutation into the coding sequence of another gene. This insertion simultaneously formed a “stop” codon early in the original gene (a codon that tells the ribosome to stop adding amino acids to a protein) and formed a brand new “start” codon in a different reading frame. The new reading frame ran for 392 amino acids before the first “stop” codon, producing a large, novel protein. As in our example above, this new protein was based on different codons due to the frameshift. It was truly “de novo” — a new sequence.
Why was this supposed to be important? Venema continued:
In order for proteins to function, they need to fold up into stable shapes — “protein folds”. Meyer claims, based on the work of his colleague Douglas Axe, that stable protein folds are vanishingly rare — on the order of only one in 10 to the 77th power. As such, Meyer argues, evolution cannot find the needle (a functional protein) in the haystack (the vast number of functionless possibilities) … All of this hinges, of course, on just how accurate Axe’s estimate is: are functional proteins really that rare?…
So if nylonase arose by frameshift mutation, via a single base insertion, producing a novel sequence and a stable, functional fold, it would appear that functional, stable folded proteins are not rare. Venema said:
…this brand-new protein [nylonase] folded into a stable shape, and acted as a weak nylonase. Later duplications, mutations and selection would make a very efficient nylonase from this starting point. Additionally, the three-dimensional structure of the protein has been solved using X-ray crystallography, a method that gives us the precise shape of the protein at high resolution. Nylonase is chock full of protein folds — exactly the sort of folds Meyer claims must be the result of design because evolution could not have produced them even with all the time since the origin of life.
Put another way, if only one in 10 to the 77th proteins are functional, there should be no way that this sort of thing could happen in billions and billions of years, let alone 40. Either this was a stupendous fluke (and stupendous isn’t nearly strong enough of a word), or evolution is in fact capable of generating the information required to form new protein folds.
And if this can happen in 40 years, what might millions of years of evolution produce? [Emphasis added.]
Venema was merely repeating the old story that has long circulated around many anti-ID websites. It goes back to 1984, when Susumu Ohno first proposed a frameshift mutation as the cause of the new nylonase enzyme.
Venema made nylonase a key element in his argument against intelligent design. He repeated the story in another post this past January (“Biological Information and Intelligent Design: evolving new protein folds”), and in his recent book, Adam and the Genome, where he said:
…what would truly settle the issue is a concrete example of a “truly new” gene coming into being — one that is not a duplicate of a preexisting protein sequence — that nonetheless has a new function and new protein folds. If scientists could observe such an event, then it would indicate that Axe’s math (and Meyer’s use of it) is not a reliable estimate for the prevalence of functional protein folds.
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.
So I began to dig in the literature. What I found was a major block across the road of the old nylonase story. To get the full picture, I’d suggest reading this post I wrote, “The Nylonase Story: When Imagination and Facts Collide,” back in May. It is based on the paper by Negoro et al. describing nylonase’s structure. The paper makes clear that nylonase was a variant of a pre-existing β-lactamase fold, not a novel protein fold. In fact, among the different kinds of β-lactamases, nylonase most resembled carboxylesterases. It was then found that nylonase had previously undetected carboxylesterase activity.
In other words, nylonase had started out as a carboxylesterase, then evolved the ability to degrade nylon byproducts. The title of the paper, and its Abstract, should make the truth obvious:
X-ray crystallographic analysis of 6-aminohexanoate-dimer hydrolase: molecular basis for the birth of a nylon oligomer-degrading enzyme.
Here, we propose that amino acid replacements in the catalytic cleft of a preexisting esterase with the β-lactamase fold resulted in the evolution of the nylon oligomer hydrolase [nylonase].
Nylonase did not have a frameshifted new protein fold. It was a pre-existing fold with activity characteristic of its fold type. No novel protein fold had emerged. And no frameshift mutation was required to produce nylonase. To quote my post:
Where did the nylon-eating ability come from? Carboxylesterases are enzymes with broad substrate specificities; they can carry out a variety of reactions. Their binding pocket is large and can accommodate a lot of different substrates. They are “promiscuous” enzymes, in other words. Furthermore, the carboxylesterase reaction hydrolyzes a chemical bond similar to the one hydrolyzed by nylonase.
From Kato et al. (1991):
“Our studies demonstrated that among the 47 amino acids altered between the EII and EII’ proteins, a single amino acid substitution at position 181 was essential for the activity of 6-aminohexanoate-dimer hydrolase [nylonase] and substitution at position 266 enhanced the effect.”
So. This is not the story of a highly improbable frame-shift producing a new functional enzyme. This is the story of a pre-existing enzyme with a low level of promiscuous nylonase activity, which improved its activity toward nylon by first one, then another selectable mutation. In other words this is a completely plausible case of gene duplication, mutation, and selection operating on a pre-existing enzyme to improve a pre-existing low-level activity, exactly the kind of event that Meyer and Axe specifically acknowledge as a possibility, given the time and probabilistic resources available. Indeed, the origin of nylonase actually provides a nice example of the optimization of a pre-existing fold’s function, not the innovation or creation of a novel fold.
The data described in the Negoro et al. and Kato et al. papers build a brick wall right across the path of Venema’s argument. And sadly, that roadblock pre-existed Venema’s posts. If he had looked carefully he would have seen it.
What do you suppose Venema’s reaction was to this collision of imagination and fact? He responded by saying, essentially, “Move on, nothing to see here.” A combination of selective retelling, sleight of hand, redirection, and downgrading the importance of the nylonase story were his main techniques. Let’s take Venema’s final post on nylonase a bit at a time to see how he did it. Dated May 18, 2017, it bears the headline:
Biological Information and Intelligent Design: New functions are everywhere
He begins with the canonical story, simply restated. No mention of the contrary facts.
In previous posts in this series, we’ve explored the claim made by the Intelligent Design (ID) movement that evolutionary mechanisms are not capable of generating the information-rich sequences in genes. One example that we have explored is nylonase — an enzyme that allows the bacteria that have it to digest the human-made chemical nylon, and use it as a food source. As we have seen, nylonase is a good example of a de novo gene — a gene that arose suddenly and came under natural selection because of its new and advantageous function. Since nylonase is a folded protein with a demonstrable function, it should be beyond the ability of evolution to produce, according to ID.
But Venema did notice I was writing about the subject. I assume he read what I wrote.
The implications of nylonase for ID arguments are clear, and they have caught the notice of several ID supporters. In recent weeks a number of posts on the subject have appeared on ID websites. ID biologist Anne [sic] Gauger, for example, is writing a series of posts in an attempt to rebut the evidence that nylonase is in fact a de novo gene. Her motivation for this work is clear. [Emphasis added.]
But at this point, oddly enough, rather than describe and refute my arguments, he changes the subject. He spends the rest of the post discussing a new paper that deals with other data regarding the ease with which random sequences benefit bacteria. He only mentions nylonase to dismiss it, in the closing paragraphs.
As we can see, the issue at hand is not so much the specific origins of nylonase, but rather the relative ease by which new, functional proteins can come into existence. If it is easy to evolve them, ID advocates are wrong. If new protein functions are vanishingly rare and inaccessible to evolution, ID would be strongly supported. With nylonase, we are dealing with events that happened in the past, so our inferences are limited to working with the evidence we have in the present.
So, we can see that the nylonase issue is something of a distraction — a missing of the forest to focus on one particular tree. Even if this particular example could have an alternate explanation, as Gauger argues, the problems for ID do not go away. [Emphasis added.]
This is a classic tactic. When shown to be wrong about nylonase, Venema changes the subject. Now nylonase is something that happened in the past, he says, implying we can’t reliably make inferences about it. He even says that nylonase is a “distraction” — despite his own repeated use of the nylonase story in trying to argue against Stephen Meyer and Doug Axe.
So as to acknowledge what Venema did talk about, I offer a few comments about the issue of functional, random sequences. Venema described the results of a recent study where a very surprising number of random sequences were reported to confer a fitness advantage on cells expressing them. I have my doubts about these results and will address them on another occasion. But I am not the only one who should be having doubts. Whatever those proteins or RNAs are doing, it is unlikely to be via a stable functional fold.
François Jacob wrote a famous essay, “Evolution and Tinkering,” in which he said, speaking of the time when the first primitive cells had emerged:
New functions developed as new proteins appeared. But these were merely variations on previous themes. A sequence of a thousand nucleotides codes for a medium-sized protein. The probability that a functional protein would appear de novo by random association of amino acids is practically zero. In organisms as complex and integrated as those that were already living a long time ago, creation of entirely new nucleotide sequences could not be of any importance in the production of new information. [Emphasis added.]
I am not denying the existence of de novo genes — ORFan genes, for example, are undeniable. 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.