In a podcast on the show, ID the Future (March 14, 2017), Dr. Ann Gauger criticized a popular argument that purports to show how easy it is to get new proteins: namely, the evolution, over a relatively short 40-year period, of nylonase. (Nylonase is an enzyme that utilizes waste chemicals derived from the manufacture of nylon, a man-made substance that was not invented until 1935.) While Dr. Gauger made some factual observations that were mostly correct, her interpretation of these observations fails to support the claim made by Intelligent Design proponents, that the odds of getting a new functional protein fold are astronomically low, and that it’s actually very, very hard for new proteins to evolve. Let’s call this claim the “Hard-to-Get-a-Protein” hypothesis (HGP for short).
To help readers see what’s wrong with Dr. Gauger’s argument, I would like to begin by pointing out that for HGP to be true, two underlying claims also need to be correct:
1. Functional sequences are RARE.
2. New functions are ISOLATED in sequence space.
In her podcast, Dr. Gauger cites the work of Dr. Douglas Axe to support claim #1, when she declares that the odds of getting a new functional protein fold are on the order of 1 in 10^77 (an assertion debunked here). Dr. Gauger says little about claim #2; nevertheless, it is vital to her argument. For even if functional sequences are rare, they may be clustered together – in which case, getting from one functional protein to the next won’t be so hard, after all.
If claims #1 and #2 are both correct, then getting new functions should not be possible by step-wise changes. Remarkably, however, this is precisely what Dr. Gauger concedes, in her podcast, as we’ll see below.
Scientific explanations for the origin of nylonase: a short history
Let me begin by providing my readers with a little background information, from a 2009 article in New Scientist magazine by Michael Le Page:
Nylon was first made in 1935. Just 40 years later, in 1975, a bacterium was discovered that is able to digest and live off not nylon itself, but waste chemicals from its manufacture – chemicals that had not existed before nylon production began.
It was later shown this bacterium, now known as Arthrobacter KI72, has evolved several types of enzymes capable of utilising these waste products. One type, 6-aminohexanoic acid hydrolase, encoded by genes called nylBs, has become known popularly as “nylonase”.
So, how did nylonase evolve? Back in 1983, a team of Japanese scientists proposed that nylonase evolved through a gene duplication and frame shift, caused by the insertion of a single base. Shortly afterwards, Dr. Susumu Ohno defended the “frame shift” hypothesis for the origin of nylonase in PNAS, in a now-famous 1984 paper.
However, a team led by Seiji Negoro of the University of Hyogo, Japan, came up with a different explanation in 2005: they claimed that nylonase actually resulted from from two point mutations in the active site of an existing carboxyl esterase enzyme. It turned out that nylonase is very similar to a common type of enzyme which breaks down natural antibiotics (known as beta-lactamases) that are produced by many different kinds of organisms. Two amino-acid changes – two mutations, in other words – were sufficient to change the beta-lactamase binding-site to a site which was capable of binding a by-product of nylon.
That makes sense. As David Wynick of the University of Bristol points out, it is generally easier to adapt an existing protein to a new function than to wait for a de novo mutation that will generate a completely new reading frame.
However, even if the frame shift hypothesis isn’t required to explain the evolution of nylonase, scientists have other well-established examples of de novo genes from alternate open reading frames. Here are two recent papers on the subject: Evolution: Dynamics of De Novo Gene Emergence (Current Biology, Volume 24, Issue 6, pR238–R240, 17 March 2014) and Concomitant emergence of the antisense protein gene of HIV-1 and of the pandemic (Proceedings of the National Academy of Sciences U.S.A., 2016 Oct 11; 113(41): 11537–11542). I wonder what Dr. Gauger would have to say about these cases.
Dr. Gauger’s puzzling admission – and the problems it generates
And now, here’s how Dr. Gauger responded to interviewer Sarah Chaffee’s question, “So, does nylonase shown that purely natural processes can create a new protein?”, in her podcast:
No. I would say, ‘Of course not,’ because we have an explanation for how it came about, through just natural modifications and selection from a starting protein – a starting enzyme, carboxyl esterase. Step-wise path, there you go. But not a frame shift. A frame shift would create a completely novel sequence, a completely novel fold, if it folded at all. And so we have no need of that hypothesis.
I note in passing that Dr. Gauger rejects an explanation for the origin of nylonase that was formerly accepted by Dr. William Dembski back in 2005, when he wrote: “Nylonase appears to have arisen from a frame-shift in another protein.” I also note that Dr. Gauger refers to “a kind of bacterium capable of digesting nylon” (2:35) and to “a whole new enzyme capable of degrading nylon” (2:44), when in fact, what the bacteria digest and live off is not nylon itself, but waste chemicals derived from its manufacture. But let us continue.
In the passage above, Dr. Gauger makes the damaging admission that natural processes can generate a new protein by a step-wise process from a starting protein, carboxyl esterase (also known as nylB-prime). That tells against claim #2 above, that new functions are ISOLATED in sequence space. For if functions really are isolated in sequence space (as Gauger, Axe and Meyers have argued previously), then how is it possible that the researchers easily found two mutations to switch nylB-prime to nylonase? That should be impossible.
In her podcast, Dr. Gauger makes much of the fact that nylonase has two open reading frames (ORFs) going in a forward direction, plus a third open reading frame going in the reverse direction. But if functional proteins are so rare, as she alleges, then how is it even possible to have overlapping ORFS? This type of bi-directional reading of information is ubiquitous in DNA, but it is much more difficult in English text. What this bi-directional reading indicates is that proteins are not so rare, after all – which undermines claim #1 above.
It should also be pointed out that the proteins described by Dr. Gauger in her podcast actually contain a high number of repeats – a point acknowledged by Dr. William Dembski back in 2005, when he described the DNA sequence of nylonase as “a very repetitive sequence.” In other words, the DNA from which this protein is generated is low-information DNA. Again: how is it possible that repetitive, low-information DNA can give rise to a new protein? Shouldn’t this be impossible? Aren’t proteins supposed to be rich in information?
Here’s another awkward question: why does nylB-prime (the protein from which nylonase evolved) appear to have no similar-looking homologs? Dr. Gauger thinks it’s because this protein is ancient. If that were the case, then we should expect to see evidence of its history in a large number of sequence-similar proteins, but we do not see this. Where did all those proteins go? What happened to them?
Finally, how is it that two genes with no homology can sometimes possess nearly the same structure and function? This shows that there are multiple sequence families that are capable of producing the same function, in the same way – which surely counts against the claim that functional sequences are RARE.
Some brief comments on Sal Cordova’s post
I mentioned above that several different kinds of enzymes have evolved in recent decades, which are capable of utilizing nylon waste products. These enzymes are known as NylA, NylB and NylC. However, none of them appear to have significant sequence homology. In a recent post, Sal Cordova puts forward a two-fold argument:
1. NylA, B, C have no homology, so they had to have had different evolutionary origins.
2. We do not know for sure if nylonase existed in nature before, because we aren’t able to go back in time.
Point #1 simply shows that evolving new proteins is easy. The fact that it has happened multiple times is not evidence against evolution, but rather, evidence that evolving new functions is a relatively straightforward matter.
Regarding #2: we know that nylon is a man-made material which does not exist in nature. It would be exceedingly strange if nylonase existed before nylon. That’s why most scientists think that these are new genes.
Finally, I’m not sure I understand the alternative model that Sal is proposing. Does he really believe that these three enzymes were hanging around for thousands of years with no function? Or does he believe that they had a hitherto-unknown function, which science will uncover?
In fact, scientists have frozen bacteria samples from before 1935 – and it isn’t even hard to obtain them. Thus it should be possible to check for the presence of nylonase in those samples. If Sal managed to identify a naturally produced nylon, then that would certainly explain why nylonase had to exist before synthetic nylon, and would suggest that these three enzymes (NylA, NylB and NylC) are not newly functional proteins, but ancient ones. However, he needs to go out and find that evidence. At the present time, scientists are not aware of any natural source of nylon.
Neither Dr. Gauger’s podcast nor Sal Cordova’s substantiates the HGP hypothesis. (NOTE: As Sal correctly notes below [here and here], his post was never intended as an argument for the HGP hypothesis.) For now, it appears that the evolution of new proteins in Nature is – at least sometimes – fairly easy, after all.
What do readers think?
UPDATE: John Harshman has kindly posted a plausible sequence of events for the evolution of nylonase, here, from an earlier comment on Sal Cordova’s thread. As he correctly points out, “the frame shift hypothesis, gene duplication hypothesis, and the two-mutation hypothesis are not mutually exclusive.” Harshman considers it most likely that “all three of these occurred some time in the evolution of NylB.”