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Pieces of the RNA World, Part 1 (of 2)

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

Sometimes bad things happen in life and the best we can do is pick up the pieces and move on. Recently a team of Italian biochemists did just that, literally.

These researchers claimed to have discovered a solution to a serious problem confronting the RNA world hypothesis, one of the leading evolutionary explanations for the origin of life. They demonstrated a conceivable way that small pieces of RNA could combine to form larger RNA 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 to build a case for the RNA world model.

Ironically, instead of supporting the evolutionary paradigm, this new work actually exposes fundamental problems with the RNA world hypothesis. When the details of the experiments are evaluated with the conditions of the early Earth in mind, the results undermine the model.

Steps to the Origin of Life

From a naturalistic perspective, the emergence of large, complex information-rich molecules is vital to life’s beginning. In contemporary living systems these molecules include proteins, DNA, and RNA, which are collectively responsible for directing and carrying out life’s most basic and central activities.

Proteins serve as the workhorse molecules of life. They play key roles in virtually every cellular function and help form nearly every cellular structure. Even the simplest life-form requires around 2,000 different types of proteins (which often occur as multiple copies) to exist as a free-living, independent organism. The cell’s machinery uses information housed in DNA to make proteins.

DNA has one other property critical for life: the ability to direct its own replication. This characteristic, called self-replication, allows the information needed to guide the cell’s activities to be transmitted to the next generation via cell division.

Some origin-of-life researchers believe that information-rich molecules emerged before other molecules. They argue that some kind of self-replicator arose early on. Replicator-first enthusiasts propose that the self-replicator materialized as a “naked” replicator that later became encapsulated within a membrane system along with the precursor molecules needed to sustain its activity. Metabolism subsequently emerged as a means to support the production and turnover of the replicator’s building blocks and, ultimately, its self-replicating activity.

(Metabolism defines the entire set of chemical pathways in the cell. The foremost of which are pathways that involve the chemical transformation of relatively small molecules. These pathways (1) generate chemical energy through the controlled breakdown of fuel molecules like sugars and fats; and (2) produce, in a stepwise fashion, the building blocks needed to assemble proteins, DNA, RNA, and cell membrane and cell wall components.)

One of the main concerns of replicator-first adherents is identifying the first self-replicator and other information harboring molecules.

A Chicken-and-Egg Problem

Before the 1980s, scientists debated whether it was DNA or proteins that appeared as the first replicators. This controversy spawned what experts call the “chicken-and-egg” problem. This conundrum refers to the complete interdependence that proteins and DNA have on one another when it comes to their synthesis and biochemical roles in the cell. Even though scientists refer to DNA as a self-replicating molecule, its synthesis, and hence its replication, require a suite of proteins. In other words, proteins reproduce DNA. On the other hand, proteins depend upon DNA for their own production, because DNA contains the information that the cell’s machinery uses to make them. That is, without DNA the cell cannot produce proteins. Because of these molecules’ mutual codependence, origin-of-life scenarios must account for the simultaneous appearance of DNA and proteins, since it is difficult to envision a scenario that involves either class of molecule existing apart from the other.

The RNA World Hypothesis

In contemporary biochemistry, many scientists find that RNA solves this chicken-and-egg problem. RNA assumes the role of an intermediary in protein formation by conveying the information stored in DNA to the cell’s protein-making systems.

Many origin-of-life investigators think that RNA predated both DNA and proteins as the premier replicator and information-harboring molecule. Accordingly, RNA operated as a self-replicator that catalyzed its own synthesis. The RNA world hypothesis supposes that over time numerous RNA molecules, representing a wide-range of catalytic activity, emerged. At this point in life’s history biochemistry centered exclusively on RNA. With time, proteins (and eventually DNA) joined RNA in the cell’s arsenal. During the transition to the contemporary DNA-protein world, RNA’s original function became partitioned between proteins and DNA, and RNA assumed its current intermediary role. RNA ancestral molecules presumably disappeared without leaving a trace of their primordial existence.

In the mid 1980s the discovery of RNA molecules with enzymatic activity (called ribozymes) propelled the RNA world hypothesis to prominence. Since then, several scientists have produced a number of ribozymes with a limited range of potential biological activity. For many origin-of-life researchers this adds more credibility to the RNA world scenario.

Evidence Needed

The RNA world hypothesis may well be the most important idea in the origin-of-life arena. With this in mind, much research focuses on identifying chemical routes to produce prebiotic compounds and condensation reactions that have the potential to lead to RNA.

Minimally, four things are required to substantiate this scenario:

  • reasonable prebiotic chemical routes that will generate the building blocks (nucleobases, ribose, and phosphate) of RNA;
  • reasonable prebiotic routes that will assemble RNA from its building blocks into molecular chains long enough to form ribozymes;
  • demonstration that ribozymes possess a range of catalytic activities necessary to sustain an RNA-based biochemistry;
  • and production of an RNA self-replicator.

To date, biochemists have identified reactions in the laboratory that can yield RNA building blocks and lead to the assembly of RNA molecules. Even though no one has succeeded in generating a genuine self-replicating RNA molecule, researchers have been able to produce a remarkable number of ribozymes using a process called in vitro evolution.

Yet, as Hugh Ross and I describe in Origins of Life, when the details of this work are carefully considered, it becomes evident that these reactions could have never taken place on early Earth. The laboratory experiments that yielded the RNA building blocks and assembled them into RNA molecules were all conducted under carefully-controlled, pristine conditions designed to maximize the success of the experiment rather than rigorously assess the likelihood that a chemical process could operate on the turbulent early Earth. Typically, these laboratory reactions involve strict control over temperature, pH, and concentration and ratio of reactants. Scientists select energy sources and conditions that promote prebiotic reactions, but avoid destruction of chemical products once they form unrealistic conditions for primordial Earth.

Usually, prebiotic reactions are stopped before chemical breakdown occurs. Chemists know that once a synthesis is completed if the products are not removed from the reaction they will eventually be destroyed. Researchers are often careful to exclude materials from prebiotic simulations that would have occurred on early Earth but would interfere and disrupt the reactions that take place in the lab. In other words, origin-of-life researchers have achieved faux success by “stacking the deck” in their favor.

The “evolution” of RNA molecules in the laboratory raises similar concerns. This process is directed and requires extensive worker intervention, and its success hinges on careful experiment design. It stretches the bounds of credulity to think that this process, or one like it, could ever have occurred on early Earth.

These problems are so severe that the late Leslie Orgel actually commented that “it would be a miracle if a strand of RNA ever appeared on the early Earth.”

In other words, the chief problem with the RNA world scenario is what appears to be the unwarranted involvement of scientists to get the chemistry and biochemistry to work. Next week I will examine another problem with this hypothesis, the assembly of RNA molecules large enough to function as ribozymes and the solution to this problem recently proposed by a team of Italian biochemists.

Part 1 | Part 2