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Pieces of the RNA World, Part 2 (of 2)

New Research Rescues RNA World Scenario for Origin of Life, Or Does It?

When you’re gambling and losing, one quick way to turn your fortunes around (or make matters even worse for yourself) is to bet “double or nothing.”

Recently, a team of Italian researchers took that approach in an attempt to turn their fortunes around with respect to the RNA world hypothesis, one of the leading ideas in the evolutionary origin-of-life paradigm. They demonstrated a conceivable way for small pieces of RNA to double up to form larger molecules, a necessary step if the RNA world hypothesis is to account for life’s start. From their perspective this advance allows origin-of-life researchers to continue betting on the success of the RNA world model.

Ironically, when the details of their experiments are critically evaluated against the conditions of the early Earth this new work actually exposes just what a bad gamble the RNA world hypothesis is.

Last week I described the RNA world model and briefly mentioned some of the problems associated with it. This week I will detail the work by the Italian scientists and explain why this research actually hurts the odds for the RNA world scenario, even though on the surface it seems like it helps advance the theory.

The RNA World Hypothesis

Many origin-of-life investigators think that RNA predated both DNA and proteins, making it the first replicator and information-harboring molecule. Thus, they surmise that early RNA took on the contemporary biochemical function of both DNA and proteins by operating as a self-replicator that catalyzed its own synthesis. According to the RNA world hypothesis, over time numerous RNA molecules with a wide range of catalytic ability emerged. Eventually, the RNA world transitioned to an RNA-protein world that finally gave way to contemporary biochemistry with the addition of DNA to the cell’s arsenal.

A Problem for the RNA World Hypothesis

To help substantiate the RNA world model researchers need to identify reasonable prebiotic routes that assembled RNA from its building blocks into molecular chains long enough to form ribozymes. It turns out that this requirement stands as a significant hurdle for the RNA world scenario. As Hugh Ross and I describe in Origins of Life the production of RNA chains from building blocks only takes place if the building blocks are chemically activated, making them reactive. The problem is that this scenario is completely unrealistic on the early Earth.

The inherent instability of the RNA chain causes another problem. As individual building block molecules are added to the chain, other water molecules react with the RNA (a process called hydrolysis), breaking the chain down. In other words, competing reactions of growth and degradation would prevent the chains from attaining the length needed to generate a ribozyme.

A Possible Solution

A group of Italian biochemists’ recent work suggests a way around the degradation problem. In laboratory experiments they showed that short RNA molecules could react with themselves in water to produce RNA molecules that are twice and four times the length of the original chemical species. Such a dramatic doubling in length would have allowed prebiotic RNA molecules to increase in size as their growth outpaced their breakdown.

The reaction between the short RNA pieces in water was unexpected because an aqueous environment promotes breakdown of the RNA chains, not growth. The researchers think that they understand how the doubling and quadrupling reactions take place. It appears as if the RNA chains pair in solution to form duplexes and quadraplexes in which the RNA chains align. In these configurations, chemical groups on the ends of the RNA molecules are in close proximity and readily react with each other to extend the chain length. The pairing of the RNA molecules creates a local environment for the reactive chemical groups that differs from what they would experience free in solution.

Evidence for Evolution or Intelligent Design?

This newly recognized reactivity of RNA fragments seems to provide important support for the RNA world scenario. The dramatic increase in RNA chain lengths by this mechanism in an aqueous environment could lead to RNA molecules that are large enough to serve as ribozymes.

It’s clear that the researchers demonstrated that, in principle the chemical pathways to extend the chain length of RNA molecules exist. But when the specifics of this new research are more carefully considered, it’s hard to envision how this type of chemistry could happen under the conditions of the early Earth.

It turns out that the doubling and quadrupling of RNA fragments is a fastidious process highly dependent upon temperature, pH, the size and the sequence of the RNA fragments, and the presence of coreactants. For example, the research team showed that formation of the duplexes and quadraplexes (needed to bring the appropriate chemical groups into close enough proximity to react) required lower temperatures and acidic or neutral pH values. At higher temperatures and alkaline pH the RNA complexes do not form. Additionally, the original chemical species chains must be 10 subunits or longer in order for the RNA fragments to couple to create duplexes and quadraplexes. The researchers also discovered that RNA fragments of unequal length form less-stable aggregates and are consequently less likely to combine. The investigators also discovered that they could improve the efficiency of the reaction by adding cofactors, small molecules with structures closely related to the structure of the subunits of the RNA fragments. It appears as if the cofactors help stabilize the RNA complexes.

In other words, if not for the careful design and execution of the reactions under laboratory conditions–carefully controlled by the researchers–the RNA fragments won’t couple together. And from an evolutionary point-of-view this type of control wouldn’t have existed on early Earth. It’s as if the researchers fixed the bet for the RNA world scenario. The biochemists also observed that the degradation of the RNA fragments took place simultaneously with the coupling reactions. This observation means that any conditions that deviate from optimal will hamper the efficiency of the coupling reactions resulting in the net breakdown of the RNA fragments.

There is one other concern. The researchers never accounted for the formation of the RNA fragments. As I pointed out earlier, the production of RNA chains requires chemically activated building blocks. These starting materials would never have existed on early Earth. In this study, the investigator used chemically synthesized RNA fragments. Production of RNA through this route, too, requires intelligent agency. (See a recent article I wrote about the chemical synthesis of DNA.)

Given how much researcher involvement is required to generate RNA molecules with sufficient length to serve as a ribozyme, my bet is that a Creator brought life into being. Double or nothing, anyone?

Part 1 | Part 2