20.8: Origins of Life Chemistries in an RNA World

Following the origins of organic monomers in a reducing environment in the tidal pool scenario, the energy for polymer formation came from cycling temperatures on an overheated Earth. In that scenario, we considered how chains of nucleotides could be synthesized and even replicated to form populations of nucleic acids with similar sequences. But if the prebiotic environment was non-reducing, where would the energy have come from to make any polymers, let alone ones that could replicate themselves? If you guessed that the energy was provided by a proton gradient between biofilm-enclosed acidic proto-cells and an alkaline ocean…, you would have been right! In this case, polymers would have been synthesized in enclosed spaces, and not in tidal pools only to be dispersed and diluted in the wider oceans. But then, how would replicative, informational, and catalytic chemistries have arisen from these organic monomers and polymers? Polypeptides would have formed, but they have no inherent chemical or structural basis for self-replication. Unlike polypeptides, we saw in describing the tidal pool scenario that polynucleotides (nucleic acids) do! In fact, as we have already seen, evidence is accumulating to support the hypothesis that life (and its first genome) originated in a RNA world:

• Glycoside bond synthesis between prebiotic bases and sugars may have been possible.
• Today’s RNAs include ribozymes that catalyze their own replication self-splicing introns).
• Some RNAs are part of ribonucleoproteins that have at least co-catalytic activities, like ribosomes, the small ribonucleoproteins (snRNPs) in spliceosomes, and the secretory signal recognition particle.
• Retroviruses (e.g., HIV) store their genetic information in RNA genomes that may have been integral to the emergence of cellular life.

Ribozymes, ribonucleoprotein structures, and retroviruses may be legacies of a prebiotic RNA world. In fact, in an ‘in vitro evolution study’, self-replicating ribozyme polymerases in a test tube become more efficient at replicating a variety of increasingly longer and more complex RNAs over time. For more about these autocatalysts that support an RNA world, check out Real & Artificial Ribozymes Catalyze RNA synthesis.

There are hypothetical RNA world scenarios for the origins of replicating, catalytic polymers, and even a real organic chemical, an autocatalyst that can catalyze its own synthesis. So, which may have come first? A self-replicating RNA or other self-replicating organic molecule? Arguably, chemical evolution of an autocatalytic RNA is a stretch, but at least one organic molecule, Amino Adenosine Triacid Ester (AATE), is a present-day selfreplicating autocatalyst. Could a molecule like AATE have been a prebiotic prelude to the RNA world? Figure 20.12 (below) shows the structure and replication of AATE.

Figure 20.12: Aminoadenosine triacid ester (AATE) catalyzes its own replication by the mechanism suggested here.

The replicative reaction proceeds in the following steps:

1. An aminoadenosine triacid ester molecule binds a second aminoadenosine.
2. A second triacid ester molecule binds to “di-aminoadenosine triacid ester”. The two aminoadenosines, now in opposite orientations, can attract and bind a second triacid ester.
3. After bond-rearrangements, the “di-aminoadenosine, di-triacid ester” molecule separates into two molecules of AATE.

This reaction is catalytic because the stereochemistry of the reacting molecules creates an affinity of the AATE molecule first for another free aminoadenosine molecule. The structure formed allows (i.e., catalyzes) linkage of a second free triacid ester, leading to the separation of two AATE molecules. Subtle, sequential changes in the molecular conformation of the molecules result in the changes in affinities of the molecules for each other. In the replicative reaction, the AATE, free ester and free aminoadenosine concentrations would drive the reaction. Could AATE-like molecules have been progenitors of autocatalyzed polymer replication? And before that, could something like reduced NAD (NADH) have supplied free energy to fuel AATE synthesis in the first place? After all, it too contains a nucleotide! Could replication of a prebiotic AATE-like molecule then have led to an RNA world? Could primitive RNAs have been stabilized by binding to short prebiotic peptides, becoming forerunners of ribozymes? The possibility of a prebiotic AATE-like precursor to an RNA world is intriguing because the ‘triacid’ includes the purine adenosine! On the other hand, the possibility of prebiotic replicating RNA-peptide complexes implies the origins of life in an RNA-Protein world (rather than exclusively RNA-world)! Whether life began in an RNA world or an RNA-protein world, catalyzed replication is of course another property of life.

353 AATE: An Autocatalytic, Self-Replicating Organic Molecule