The ribosome is a ribozyme? Yes and No

The peptidyl transferase center (PTC) of all ribosomes comprises catalytic RNA. Evidence in favor of “the ribosome is a ribozyme.”

But I would welcome the comments of Art, John Mercer, T. aqua, and others who care about this question, on the following exchange. The speakers here are George Church, Craig Venter, and the late Robert Shapiro:


CHURCH: But isn’t it the case that, if we take all the life forms we have so far, isn’t the minimum for the ribosome about 53 proteins and 3 polynucleotides? And hasn’t that kind of already reached a plateau where adding more genomes doesn’t reduce that number of proteins?

VENTER: Below ribosomes, yes: you certainly can’t get below that. But you have to have self-replication.

CHURCH: But that’s what we need to do — otherwise they’ll call it irreducible complexity. If you say you can’t get below a ribosome, we’re in trouble, right? We have to find a ribosome that can do its trick with less than 53 proteins.

VENTER: In the RNA world, you didn’t need ribosomes.

CHURCH: But we need to construct that. Nobody has constructed a ribosome that works well without proteins.

VENTER: Yes.

SHAPIRO: I can only suggest that a ribosome forming spontaneously has about the same probability as an eye forming spontaneously.

CHURCH: It won’t form spontaneously; we’ll do it bit by bit.

SHAPIRO: Both are obviously products of long evolution of preexisting life through the process of trial and error.

CHURCH: But none of us has recreated that any.

SHAPIRO: There must have been much more primitive ways of putting together
catalysts.

CHURCH: But prove it.


(source: Life: What A Concept! | Edge.org )

John Harshman, in another thread, said that someone had digested away all the proteins from a ribosome in vitro, and what remained (the RNAs) still functioned. I would be very interested in seeing that publication, if anyone can find it (I couldn’t).

I don’t want to accuse Art and John Mercer of begging the question, but their statements in another thread, namely, that there is no question that the ribosome is a ribozyme, remind me of this imaginary exchange:

Joe: An automobile engine is just a gas fire.

Moe: Say what?

Joe: Combine oxygen and gasoline, provide a spark – bingo, power. The rest is just details and decorations.

But can you paint like Titian?

So far I can’t either. But Church, oddly, seems to imply the same thing:

Why “works well” rather than just “works”? We would all agree that the proteins improve ribosomal function. But a ribosome that works, even poorly, without proteins is still a working ribosome, and we are also seeing only rRNAs that have adapted to the presence of those stabilizing proteins. This supposed floor on the number of ribosomal proteins observed in living organisms is just the observation of an adaptive peak while implying that there are no adaptive slopes.

1 Like

I would want to see “works,” if “works” can be demonstrated. That would be a major boost for the RNA World hypothesis.

2 Likes

Thanks, Art.

So are we agreed that the RNA World hypothesis has received a major boost?

5 Likes

@pnelson, why do you cut-and-paste an exchange that seems to focus on a straw man argument, while not mentioning much better-informed and exciting ideas from people who work in the field. The objections you seem to be raising are addressed - theoretically, hypothetically, and as time passes experimentally - by researchers who actually work in this field. At the risk of offending @Eddie’s sensibilities re broken records, Loren William’s work is a much better basis for discussion and debate than the snippet you gave. And, I would add, the successes and prospects are much, much greater than you are letting on.

2 Likes

Art,

I have personally linked to Loren Williams’s work on ribosomal evolution at this discussion site (as you know). But if the “straw man” erected by George Church has been knocked over, I’d like to know by whom.

I need to download and read the 1992 Science paper, for which you helpfully provided the citation, before I can answer John Harshman’s question. In vitro is not in vivo, and everything turns on what can be shown in the latter case.

Not really no. Even were it the case that the modern ribosome could not be made to function in the total absence of it’s modern protein components, that would not entail that there was not a stage earlier in it’s evolution where it did function in the absence of protein.

There’s really no reason a priori why you should expect a stripped and reduced version of a modern ribosome to function in a cellular context to which it has adapted over the course of ~4 billion years, unless you also change the whole surrounding cellular context to be like it was when the ribosome was that much simpler.

It’s sort of like cutting off the arms, legs, and eyes of a person, and then expecting that bleeding torso to constitute a sensible facsimile of the “worm” stage from which we evolved. Oh look, it’s bleeding to death, worms are impossible!

6 Likes

I see that as an excuse, nothing more.

1 Like

In vitro versus in vivo is the only relevant question. Recall that the claim on the table is this: the ribosome is a ribozyme.

Not the PTC, for which the evidence of the role of catalytic RNA is undisputed. The ribosome itself, of which the PTC is a part – central, to be sure, but no more the whole story of translation than combustion (gasoline + oxygen + ignition) is the whole story of an internal combustion engine.

Anyway, I read the Noller et al. paper. A model peptide bond was formed in what the authors call the “fragment reaction,” using chemical analogues to peptidyl tRNA and aminoacyl-tRNA. Highly simplified assay, showing what I never disputed, namely, that peptide bond formation in ribosomes is catalyzed by RNA.

What the experiment does not provide is an explanation for the universal pattern noted by George Church, above: all known ribosomes have dozens of protein components, and no one has ever shown that, in vivo, translation occurs without those proteins.

Unless one assumes the point at issue, and marries the data to the RNA World hypothesis:

There’s really no reason a priori why you should expect a stripped and reduced version of a modern ribosome to function in a cellular context to which it has adapted over the course of ~4 billion years, unless you also change the whole surrounding cellular context to be like it was when the ribosome was that much simpler.

1 Like

@pnelson, maybe you can summarize the evidence - in vivo and/or in vitro - that shows that one or more of these proteins play central roles in the peptidyl transferase reactions.

Then we can weigh these with the very compelling evidence (in vitro and in vivo, the latter being the effects of PTC RNA mutations) that shows that the ribosome is a ribozyme.

2 Likes

So what? All that shows is that ribosomal proteins have a function. It doesn’t show that they were necessary in ancestral ribosomes and it doesn’t show that a ribosome would not function without proteins. The fact that an RNA-only ribosome can function at all is an argument for the RNA world.

3 Likes

I’m not assuming the point at issue, I’m explaining why your proposed test is not capable of yielding a result that would undermine the RNA world hypothesis.

2 Likes

The exchange that includes Church’s musings have nothing to do with the fact that ribosomes are ribozymes. And the remarks certainly raise no doubts - none whatsoever- about this fact. Which is, as far as I can see, the point of contention here.

1 Like

The “universal pattern” has nothing to do with the fact that ribosomes are ribozymes. Moreover, this fact does not assume the RNA World, but rather leads inexorably down that path.

It is pretty revealing the ferocity with which ID proponents deny this fact. Revealing because it shows that ID is all about evolution NO, about denying the universal common ancestry of life.

Look at things from a different perspective. By now, it is clear that, in general, biochemical functionality is not the impossibly rare commodity that ID theory demands. But it remains a formal possibility that, hidden in the sea of function we see in life is the one (or few) “rare” biochemical entities. The very obvious candidate for such a function, one that roots all life, is the PTC. An enterprising ID proponent would (and, IMO, should) be formulating testable hypotheses that focus on the function and origins of the PTC. And not expending thought denying what we know about ribosomes because it offends the anti-evolution sensibilities that dominate the ID camp.

(Since I am on this tangent, I would further note that this one foundation of ID theory, that function in general is impossibly rare, has been known to be wrong for more than 20 years. I have thought that an excellent niche for ID-friendly scientists would have been to develop new experimental and especially computational tools to systematically sort through sequence space so as to “find” truly rare functions. That this has not happened is, IMO, a tremendous and lost opportunity. One lost because ID is really about evolution denial.)

3 Likes

I want to see your ID explanation for the fact that you agree with:

Can you or any of your colleagues explain that as a design?

And you really have no explanation for this as an intelligent design.

Science really isn’t about claims. It’s about testing hypotheses. This represents a very successful prediction of the RNAW hypothesis. It would be successful even if a residue here and there played a role in the peptidyl transferase active site.

If that’s the only relevant question, when will YOU ever do some in vivo work? It seems that you have declared yourself to be irrelevant.

You just hypothesized that it could not happen without proteins, remember? You seem to have trouble with this whole hypothesis-testing thing.

It’s also pretty revealing in that it falsifies the ridiculous claim of so many denialists (Hi, @Guy_Coe!) that both groups are simply interpreting the same evidence differently.

This is a clear case of ID creationists denying the evidence itself. Paul, do you really not know what Proteinase K and phenol do to proteins?

1 Like

To my knowledge, in addition to the catalyzation of the forming of peptide bonds between amino acids, no ribosomal protein is directly involved in the two other forms of activity carried out by the ribosome, which is the simultaneous translocation of mRNA and tRNA as they shuttle between the large and small subunits while the PT-center strings together amino acids. These mechanisms too appear to be performed directly by RNA components. The activity is greatly accelerated by the translation factor EF-G, which is a (non-ribosomal)protein, but has been shown to not be strictly necessary for the mechanism, though it apparently runs much slower without it.

1 Like

I said translation could not happen without proteins. Peptide bond formation, and translation, are not the same process.

What was missing from the Noller et al. 1992 assay? mRNAs, tRNAs, the small subunit, etc., and the actual synthesis of a protein. The PTC comprises catalytic RNA. The PTC is not a ribosome. Only ribosomes are ribosomes.

An automobile engine is not simply a gas fire with a few bells and whistles.