RNA first theory on the rocks

A Chilling Origin of Life Scenario
Evolution News & Views

The most popular of the Origin of Life (OOL) models is the RNA-first world. RNA can have catalytic properties similar to proteins (enzymes) and are thus called ribozymes. RNA or some form of pre-RNA is an attractive early earth molecule and possible progenitor to early life because, unlike the chicken-and-egg problem with proteins and DNA, theoretically, RNA replication can be completely self-contained. In fact, in January 2009 Nature reported on the synthesis of a self-replicating RNA molecule capable of catalyzing its own replication. See Casey Luskin's report here.
There are several problems with the RNA-first model (See here for a short discussion on some problems with RNA, and see Chapter 14 in Signature in the Cell) not the least of which is how difficult RNA is to synthesize. However, two of the major problems that OOL researchers face are the inherent instability of RNA (a much less stable molecule than DNA) and the dilute reaction conditions that were likely on the early earth. A recent Nature Communications proposes a hypothesis that addresses these problems. The authors propose that perhaps these early earth RNA reactions occurred in ice.

The authors began with 18R RNA polymerase ribozyme because of its similarity to probable early earth RNA and brought their reaction solution to the eutectic phase (a specific temperature range for a particular solution) to see whether RNA replication occurs. Although the authors admit that the reaction is slowed down considerably, the sub-zero temperature stabilizes the products, and the formation of ice crystals concentrates the reactants. Overall, they obtained products in the range of 32 to 41 nucleotides, a longer RNA strand than when this reaction is conducted at room temperature.
There are several important points and assumptions made in this article:
Points:

• The temperature was brought to the eutectic phase, which is a specific temperature range for a given solution of solvent and solutes. The eutectic phase is colder than the freezing point of the solvent itself, so in this reaction the solution of solute particles and water is brought to below the freezing point of water.


• Bringing the solution to the eutectic point forms an ice-lattice structure that allows for diffusion and compartmentalization of RNA products and side products.


• Ice causes substrate and solute concentration and prevents replicase degradation. It allows for compartmentalization, and certain microstructures of the ice permit diffusion, helping the overall reaction yield. These are very specific results from a specific set of conditions.

Assumptions:

• The authors state that R18 RNA polymerase ribozyme is "the best available modern day analogue of a primordial replicase," which is based on some presuppositions on what the primordial replicase would be. Furthermore, this starting material was purified before use. One of the biggest problems with the RNA-first world is the problem of synthesizing RNA in the first place. The reactions to produce the nucleotides would inhibit the reactions to produce the ribose rings, making the synthesis complicated.


• The cold temperature slows down the reaction, but stabilizes and reduces degradation of replicase product. The authors assume that the slower kinetics is off-set by the stability of the product.


• The authors assume a cold early Earth, or at least cold portions of an early earth. The authors provide references that suggest perhaps the early earth was cold rather than hot; however, this is a contentious issue.


• An assumption that is common in OOL scenarios, from the article: "Our results imply a potentially wider role for ice, promoting all the steps from prebiotic oligomer synthesis to the emergence of RNA self-replication and Darwinian evolution." Thus far, there is no mechanism describing how to move from RNA to a nucleus-like organelle to a protocell to cellular life. This is taken for granted in origin of life scenarios.

While this is a proof-of-concept experiment, some of these assumptions are too specific or troublesome to be ignored.
For example, slowing down an already slow process when the geological clock is ticking is glossed over in this article, but needs to be considered. In these types of reactions, heating speeds the reaction up but risks destroying the products while cooling protects the products, but slows a reaction down (See also Levy and Miller, "The stability of the RNA bases: Implications for the origin of life" Proc. Natl. Acad. Sci USA vol 95:7933(1998).). OOL of life scenarios presume that even though it is highly improbable that some chemicals will randomly come together and form something functional, given enough time, there will be plenty of opportunities (probabilistic chances) for this to happen. If a reaction is slowed down, then there are fewer opportunities for chemicals to meet.
Time is taken for granted, but many scientists content that the opportunity for an origin of life scenario to occur may be in the range of 200-500 million years, short in a geological sense. The actual date of the emergence of life is a contentious issue, but many findings have pushed the date back to the earliest bacteria living 3.5 billion years ago. Furthermore, the early earth's environment was inhospitable for any kind of life or organic chemistry for the first 500 million years (For one example of reports in this field, see Schopf, J. William "The First Billion Years: When Did Life Emerge?" Elements vol 2:229( 2006).). Given the very specific conditions reported in the article and the slower reaction time, there is not enough time (probabilistic chances) for this to be a plausible origin of life scenario.
Finally, this quote from the article gives one pause if one is trying to model a naturalistic origin of life scenario:

Although ice thus more than doubles the primer extension capability of the R18 RNA polymerase ribozyme, significant further improvements are required to bring self-replication of the 195 nucleotide ribozyme within reach. While in-ice RNA replication activity may be enhanced further by continued fine-tuning of solute concentrations and identity, there is no denying that R18, in its current form, is maladapted to the ice phase.

There are many assumptions (too many) that are granted to origin of life scenarios, but the one assumption that should not be granted is "continued fine-tuning," as that negates the entire point of trying to find a naturalistic process that could have produced the earliest protocells and subsequently the earliest forms of life that would continue to evolve. Even given the author's statement that R18 was maladapted to ice, they were using a substance that they had purified, and one that earlier in the article was assumed to be as close to the early earth molecules as possible. The experimental section for this reaction is not a simple mechanism. It has very specific details on how the authors brought the reaction to the right temperature and maintained that temperature, their buffer solution, the effect of particular solute anions on the ice structure, and their work up of the reaction. With every instance of a chemist's intervention (or fine-tuning) to a reaction, one decreases one's probabilistic chances of this reaction occurring by chance.
In any origin of life scenario the problem of the chemists' presence is difficult to ignore. There comes a point when so much tweaking and fine-tuning should tell the experimenter that this reaction is too sensitive to the reaction conditions to be a viable contender in the search for the first reactions that produced life.