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The first RNA world

mRNA strands may have eventually evolved to the advanced DNA that now makes up the recipe of life. (Illustration: File/ Vossman)

The term "RNA world" was first used by Walter Gilbert to refer to a hypothetical world before DNA, in which RNA was the dominant replicating molecule. In a recent review, Thomas Cech discussed three RNA worlds, the first being the primordial world before life as we know it, the second consisting of all the current functions of RNA, and the third is the world of custom-designed and engineered RNA molecules, with a host of new functions. This blog post will examine the first RNA world, with the second and third, hopefully, to be discussed at later times.

Early molecular biologists envisioned mostly a DNA and protein world, in which DNA was the store of genetic information, while proteins provided structural support and did all the work. RNA was seen as mostly an intermediary that aided the translation of DNA information into protein sequences. This neat division started to crack when it was revealed that some viruses use RNA as their genome. David Baltimore and Howard Temin further confused the issue when they showed that RNA could function as a template for the synthesis of DNA through reverse transcriptase.

Things became more complicated still in the 1970s and 1980s when various catalytic functions of RNA were revealed, such as self-splicing RNA transcripts. Francis Crick had suggested in 1968 that the early ribosome may have been composed entirely of RNA. Later analysis of modern ribosomes revealed that the peptide bond is formed in the central core without the aid of protein catalysts. Taken together, the evidence seems to suggest that DNA and proteins may be relatively recent inventions of clever RNA molecules.

In vitro experiments have shown that certain RNA oligonucleotides can serve as templates to direct the spontaneous, non-enzymatic synthesis of complementary strands, given the availability of sufficient 5' triphosphate nucleotides. Poly-G non-enzymatically directs the synthesis of poly-C, for instance. All that is needed, really, is an RNA molecule that promotes, in some fashion, its own synthesis. From there, Darwinian natural selection can start working, leading eventually to the vast storehouse of genetic information represented by life on Earth. The process need not be too efficient at first, since there would be no nasty degradative enzymes floating around in the primeval soup.

A greater problem, perhaps, is from whence are derived the nucleotide triphosphates? Pyrimidines and purines have been found in meteorites and are probable prebiotic components, but not so the triphosphate building blocks of RNA. Matthew Powner and colleagues have shown a means to create activated pyrimidines under plausible prebiotic conditions.

Yarus has suggested a very simple sequence might be the Initial Darwinian Ancestor; something like the ubiquitous dinucleotide co-factors still in existence, nicotinamide-adenine dinucleotide (NAD) or flavin-adenine dinucleotide (FAD).

Lincoln and Joyce have demonstrated the replication of two complementary RNA ligases, each of which catalyzes the formation of the other.  Given the availability of suitable substrates, the reaction could, in theory, continue indefinitely.

Of course, at some point the replicating molecule would have to be compartmentalized to make a proto-cell.  Fatty acids will self-assemble to make micelles or vesicles. Schrum et al. have followed up suggestions that vesicles could spontaneously form in the hollow channels found in rock surrounding thermal vents. They have found that fatty acid vesicles form at the ends of capillary tubes and can retain RNA or DNA oligonucleotides at temperatures between 0 and 100 degrees Centigrade.

Synthetic biology has a ways to go before a soup of minimal components, lipids, nucleotides and amino acids, spontaneously assembles and starts growing and dividing. But the gap between laboratory chemistry and biology is shrinking.

Representative Image Caption
mRNA strands may have eventually evolved to the advanced DNA that now makes up the recipe of life. (Illustration: File/ Vossman)
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Steven A. Edwards, Ph.D.