Ragnarok for the RNA world?

As a Solution to the Origin of Life, RNA World Model Comes Under Attack

According to a recent article at New Scientist, "Why 'RNA world' theory on origin of life may be wrong after all," the RNA world model of the origin of life is under attack:

Life has a chicken-and-egg problem: enzymes are needed to make nucleic acids -- the genetic material -- but to build them you need the genetic information contained in nucleic acids. So most researchers assume that the earliest life, long before the evolution of cells, consisted of RNA molecules. These contain genetic information but can also fold into complex shapes, so could serve as enzymes to help make more RNA in their own image -- enabling Darwinian evolution on a molecular level.

At some point, the idea goes, this RNA world ended when life outsourced enzymatic functions to proteins, which are more versatile. The key step in this switch was the evolution of the ribosome, a structure that builds protein molecules from genetic blueprints held in RNA.

But such a transition would require abandoning the enzymatic functions of RNA and reinventing them in proteins. "That is not a simple model," says Loren Williams, a biochemist at the Georgia Institute of Technology in Atlanta.

That's a reasonable point at the end of the quote: If a self-replicating system has all of the enzymatic functions it needs from RNAs (something that hasn't been demonstrated), then rebuilding that system using an entirely different type of molecule (proteins) would be an extremely difficult task and highly unlikely. Yet this is essentially precisely what the classical RNA world model requires.

But there are many other criticisms of the RNA world model. A 2012 paper inBiology Direct by biochemist Harold S Bernhardt keenly titled, "The RNA world hypothesis: the worst theory of the early evolution of life (except for all the others)," notes that "the following objections have been raised to the RNA world hypothesis":

(i) RNA is too complex a molecule to have arisen prebiotically; (ii) RNA is inherently unstable; (iii) catalysis is a relatively rare property of long RNA sequences only; and (iv) the catalytic repertoire of RNA is too limited.

Now the author himself accepts the view that the RNA world is the best materialistic model for the origin of life. But he's very frank about its problems. For example, regarding the objection that "RNA is too complex a molecule to have arisen prebiotically," he writes:

RNA is an extremely complex molecule, with four different nitrogen-containing heterocycles hanging off a back-bone of alternating phosphate and D-ribose groups joined by 3',5' linkages. Although there are a number of problems with its prebiotic synthesis, there are a few indications that these may not be insurmountable. Following on from the earlier work of Sanchez and Orgel, Powner, Sutherland and colleagues have published a pathway for the synthesis of pyrimidine nucleotides utilizing plausibly prebiotic precursor molecules, albeit with the necessity of their timed delivery (this requirement for timed delivery has been criticized by Benner and colleagues, although most origin of life models invoke a succession of changing conditions, dealing as they do with the evolution of chemical systems over time; what is critical is the plausibility of the changes).

We covered the research of Powner and Sutherland here and here, pointing out that it was carefully designed to yield the desired results and noting how the goal-directed nature of the experiment undermines claims of the model's plausibility under unguided natural conditions. Hence the criticism that it has an unlikely "requirement for timed delivery."

Bernhardt then moves on to another criticism:

RNA is often considered too unstable to have accumulated in the prebiotic environment. RNA is particularly labile at moderate to high temperatures, and thus a number of groups have proposed the RNA world may have evolved on ice, possibly in the eutectic phase (a liquid phase within the ice solid).

But there's a major problem with the "cold" origin of life hypothesis: at low temperatures, reactions become so slow that nothing interesting ever happens. That's going to be a problem for many types of organic chemistry necessary for the origin of life. This is an especially significant problem when one considers that life appeared on earth very rapidly after conditions became favorable:

"...we have now what we believe is strong evidence for life on Earth 3,800 thousand million years [ago]. This brings the theory for the Origin of Life on Earth down to a very narrow range ... we are now thinking, in geochemical terms, of instant life..." (C. Ponnamperuma,Evolution from Space 1981.)

"[W]e are left with very little time between the development of suitable conditions for life on the earth's surface and the origin of life. Life is not a complex accident that required immense time to convert the vastly improbable into the nearly certain. Instead, life, for all its intricacy, probably arose rapidly about as soon as it could." (Stephen Jay Gould, "An Early Start," Natural History, February, 1978.)

A cold origin of life makes it much more difficult for life to arise under such a short timescale. Moreover, the notion that the early earth was cold rather than hot flies in the face of everything geologists have ever said about the conditions on the early earth.

Next, Bernhardt notes that "Catalysis is a relatively rare property of long RNA sequences only," and he offers a nice discussion of the gross improbability of randomly producing a long, self-replicating RNA molecule:

The RNA world hypothesis has been criticized because of the belief that long RNA sequences are needed for catalytic activity, and for the enormous numbers of andomized sequences required to isolate catalytic and binding functions using in vitro selection. For example, the best ribozyme replicase created so far -- able to replicate an impressive 95-nucleotide stretch of RNA -- is ~190 nucleotides in length, far too long a sequence to have arisen through any conceivable process of random assembly. And typically 10,000,000,000,000-1,000,000,000,000,000 randomized RNA molecules are required as a starting point for the isolation of ribozymic and/or binding activity in in vitro selection experiments, completely divorced from the probable prebiotic situation. As Charles Carter, in a published review of our recent paper inBiology Direct, puts it:

"I, for one, have never subscribed to this view of the origin of life, and I am by no means alone. The RNA world hypothesis is driven almost entirely by the flow of data from very high technology combinatorial libraries, whose relationship to the prebiotic world is anything but worthy of "unanimous support". There are several serious problems associated with it, and I view it as little more than a popular fantasy" (reviewer's report in [5]).

1014 - 1016 is an awful lot of RNA molecules.

Don't miss what's being said here: the argument directly parallels ID proponents who observe that it's extremely unlikely for an RNA molecule with just the right nucleotide sequence needed for self-replication to arise by chance. In other words, he's making the information sequence challenge to the origin of life.

Now Bernhardt proposes that perhaps the first self-replicating RNA was much shorter, reducing the probabilistic obstacles to randomly generating the right nucleotide sequence. But the evidence that this is actually possible is non-existent. Indeed, one of the reviewers, Eugene Koonin, points out that such a self-replicating RNA -- whether long or short -- has yet to be demonstrated:

I basically agree with Bernhardt. The RNA World scenario is bad as a scientific hypothesis: it is hardly falsifiable and is extremely difficult to verify due to a great number of holes in the most important parts. To wit, no one has achieved bona fide self-replication of RNA which is the cornerstone of the RNA World.

Finally, Bernhardt explains a fourth problem with the RNA world model, namely "The catalytic repertoire of RNA is too limited":

It has been suggested that the probable metabolic requirements of an RNA world would have exceeded the catalytic capacity of RNA. The majority of naturally occurring ribozymes catalyze phosphoryl transfer reactions -- the making and breaking of RNA phosphodiester bonds. Although the most efficient of these ribozymes catalyze the reaction at a comparable rate to protein enzymes -- and in vitro selection has isolated ribozymes with a far wider range of catalytic abilities -- the estimate of proteins being one million times fitter than RNA as catalysts seems reasonable, presumably due to proteins being composed of 22 chemically rather different amino acids as opposed to the 4 very similar nucleotides of RNA.

While Bernhardt discusses the various kinds of reactions that RNA can catalyze, he admits "RNAs are, in most cases, worse catalysts than proteins." That sounds like Bernhardt just conceded the validity of the criticism that he described against the RNA world. Somehow, however, he manages to spin the inferiority of RNA catalysis, turning it into not a knock against the RNA world, but an argument for it: "This [the inferior catalytic abilities of RNA] implies that their [RNA's] presence in modern biological systems can best be explained by their being remnants of an earlier stage of evolution, which were too embedded in biological systems to allow replacement easily."

So RNA is used by living organisms -- despite its inferior catalytic abilities -- only because evolution wasn't able to replace it? But aren't we constantly told how proteins can evolve to accommodate virtually any need of an organism? Doesn't this suggest severe limits to the evolvability of proteins? Now it seems that limits to evolution have become an argument forevolution.

This tortured logic brings us back to the criticism raised in the recent New Scientist article: the RNA world model is unlikely to be correct because it requires that proteins (with superior chemistry-catalyzing abilities) somehow swooped in and replaced what RNA was doing. That seems very unlikely. But Bernhardt again tries to spin this dilemma into an argument for the RNA world -- that difficulties replacing RNA with protein point to the fact that RNA was once a precursor of life. However, if it's so hard to replace RNA with proteins, how do we know that it happened in all the other cases required by the RNA world model?

It seems that whether proteins did or did not replace RNA, we're being told that in either case that's evidence for the RNA world. No wonder Eugene Koonin called the model "unfalsifiable."

So why does anyone prefer the RNA world model, given all its problems? Koonin provides the answer in his reviewer's comments at the end of Bernhardt's article -- it's because he requires some materialistic model, and other materialistic models clearly won't explain the origin of replication:

[T]he RNA World appears to be an outright logical inevitability. 'Something' had to start efficiently replicating to kick off evolution, and proteins do not have this ability.

Koonin's argument thus goes like this: We know that unguided evolution is true, so some evolutionary model must be correct. If other unguided models of life's origins won't work, then the RNA world must be correct, because "something" had to happen to get life started.

But what if the RNA world itself has many problems and so it isn't a viable solution? That's not an option Koonin seems willing to consider. He's right that "something" has to get life started. But there is a third way that Koonin hasn't considered. That third way -- the "something" he won't consider -- is the only known cause that can generate the kind of highly complex and specified digital sequences required at the origin of life: intelligent design.