University of Toronto biochemist Larry Moran was quick to respond to my post of last week, “Is Evolution True? Laying Out the Logic.” He replied on his blog Sandwalk (“A creationist argument against the evolution of new enzymes“) the same day mine was published. His post was sprinkled with his own IDiosyncratic version of mockery, but he had very little to say by way of an actual argument. Moran poked fun at my description of the argument for enzyme design (no surprise there), but he left out my version of the argument for enzyme evolution.

He did post his own version of the argument for enzyme evolution. When I read it, I was amazed by what I saw. Larry Moran had made the same evolutionary argument, step-by-step, as I had. The similarities were striking. The funny thing was, he didn’t seem to see that that was what he had done. Then again, maybe he did, because he conveniently left that particular argument of mine out of his post.

To see for yourself, you will need to compare. Read his argument, then mine. I have copied his version below, and added in parentheses his estimation of the epistemic value of each statement, or how much truth Moran assigns to each statement.

Larry’s evolutionary argument:

1. Evolution is a proven fact. It can be easily observed in the lab. (Moran: true)

2. The evidence that evolution has occurred in the past is overwhelming. This is especially true of molecular evolution. It would be perverse to ignore all this evidence and claim that genes have not evolved over billions of years. (Moran: proven fact)

3. Primitive enzymes were probably promiscuous — they were able to catalyze reactions with a large range of related substrates [The Evolution of Enzymes from Promiscuous Precursors] Many modern enzymes have broad specificity. (Moran: probable or true. He’s citing his own blog there)

4. Homologous enzymes with different, but related, specificities probably evolved from promiscuous ancestral enzymes following a gene duplication event and subsequent specialization of the two copies. Evolution in the two lineages occurs by a combination of natural selection and random genetic drift. (Moran: probable)

5. It’s possible to deduce the amino acid sequence of an ancient enzyme from a phylogenetic tree. Some ancient enzymes have been constructed and some of them react with multiple related substrates (promiscuous) as predicted. (Moran: true)

6. Therefore, it’s reasonable to conclude that homologous enzymes with different specificities can evolve from promiscuous enzymes in this manner. (Moran: highly probable?)

My version of a typical evolutionary argument for enzyme evolution is reproduced below. Remember, this argument represents the views of scientists like Moran who are deeply committed to the truth of evolution. It does not represent my views. Once again, I have added in parentheses how much truth I assign to the statement.

Ann’s presentation of the evolutionary argument:

1. Evolution is true. That is, enzymes have evolved new functions by a process of random mutation and natural selection. (Gauger: unproven assumption)

2. Modern enzymes can’t evolve genuinely new functions by random mutation and natural selection but can only tinker with existing functions. (Gauger: true. Statement supported by our research and the literature)

3. Therefore, ancient enzymes must have been different, capable of carrying out a broad range of enzyme activities. (Gauger: hypothetical statement)

4. Those enzymes underwent duplication and diverged from one another, becoming specialized. (Gauger: hypothetical statement)

5. How do we know this happened? Because we now see a broad array of specialized enzymes. Evolution is the explanation. (Gauger: circular argument)

This argument begs the question of whether evolution is true. It is circular, unsubstantiated by the evidence, and unfalsifiable. No one can know what ancient enzymes actually looked like, and whether they really had such broad catalytic specificities.

Moran’s statements #1 and #2 amply indicate that he believes evolution is true. The evidence for evolution that Moran says is so overwhelming is no doubt based on how similar things are, on the observation that they can (sometimes, considering some traits) be arranged in hierarchical groupings, and that they have changed over time. I acknowledge those facts. But that does not prove things got that way by a process of random mutation, selection, and drift. That has to be demonstrated.

He leaves out my #2, I would guess because he thinks it’s wrong. Yet protein engineers, biochemists, and molecular biologists who work in the field of enzyme evolution acknowledge this fact. See my previous post for an example; you can find more in our published papers.

The parallels between #3 and #4 are obvious. Moran wisely qualifies his statements with “probably.” However, we have no evidence for ancient promiscuity. It is a hypothesis only. The thing that Moran and I do agree about is how the diversification might have happened, if it did happen.

I dispute his #5, not because it hasn’t been done — it has — but because I don’t know how well the “putative” ancestors match the actual ones. Ancestral enzymes exist only in the deep past, so we can never know what they were like. All we can do is create possible versions, then compare them to what we expect. Here Moran refers to Thornton’s work, and other studies like his. I will grant that that work is very carefully done and interesting.

The question then becomes whether modern enzymes exhibit the range of activities necessary to account for modern diversity. Moran says modern enzymes have broad specificity. Some do, but it is usually substrate specificity, meaning they bind to different but related chemicals. Rarely do they carry out different reactions, which is a much harder thing to do. Reaction specificity is the hallmark of enzyme function. And it is the evolution of new reactions that needs to be explained. 

Lastly, #6. It is reasonable to Moran that things happened in this way because he accepts all previous statements, and because he needs an explanation for current enzyme diversity. By his lights everything he says is at least plausible or true. I give him credit therefore for couching his conclusion in the careful language of most scientific papers on the subject: “It is reasonable to conclude…”

You probably noticed that Moran and I assign different levels of epistemic value to each statement in his argument. What I see as unproven and improbable or hypothetical he sees as true or at least probable. Therefore he views his explanation for enzyme evolution as almost certainly true.

You see? Moran begins by assuming evolution is true, then hypothesizes a mechanism for how enzymes must have evolved, then concludes that his explanation is reasonable. But how much would he accept the story about ancestral proteins being promiscuous if he didn’t believe wholeheartedly that enzymes had evolved by the standard evolutionary mechanism? His conclusion is based on his stated assumption.

That circularity, you may have noticed, is precisely what I said about evolutionary logic.

Image credit: Masakazu Matsumoto/Flickr.