page_title: RNA world
section_title: Prebiotic RNA synthesis
hierarchical_section_title: RNA world / Prebiotic RNA synthesis
caption_attribution_description: English: A schematic representation of the classical RNA world hypothesis. Initially, synthesis and random polymerisation of nucleotides result in pools of nucleic acid oligomers, in which template-directed non-enzymatic replication may occur. Recombination reactions result in the generation of longer oligomers. Both long and short oligomers can fold into structures of varying complexity, resulting in the emergence of functional ribozymes. As complexity increases, the first RNA replicase emerges, and encapsulation results in protocells with distinct genetic identities capable of evolution. In reality, it is likely that multiple processes occurred in parallel, rather than in a strictly stepwise manner, and encapsulation may have occurred at any stage.
context_page_description: The RNA world is a hypothetical stage in the evolutionary history of life on Earth, in which self-replicating RNA molecules proliferated before the evolution of DNA and proteins. The term also refers to the hypothesis that posits the existence of this stage.
  Alexander Rich first proposed the concept of the RNA world in 1962, and Walter Gilbert coined the term in 1986. Alternative chemical paths to life have been proposed, and RNA-based life may not have been the first life to exist. Even so, the evidence for an RNA world is strong enough that the hypothesis has gained wide acceptance. The concurrent formation of all four RNA building blocks further strengthened the hypothesis.
  Like DNA, RNA can store and replicate genetic information; like protein enzymes, RNA enzymes can catalyze chemical reactions that are critical for life. One of the most critical components of cells, the ribosome, is composed primarily of RNA. Ribonucleotide moieties in many coenzymes, such as acetyl-CoA, NADH, FADH, and F420, may be surviving remnants of covalently bound coenzymes in an RNA world.
  Although RNA is fragile, some ancient RNAs may have evolved the ability to methylate other RNAs to protect them.
context_section_description: Nucleotides are the fundamental molecules that combine in series to form RNA. They consist of a nitrogenous base attached to a sugar-phosphate backbone. RNA is made of long stretches of specific nucleotides arranged so that their sequence of bases carries information. The RNA world hypothesis holds that in the primordial soup (or sandwich), there existed free-floating nucleotides. These nucleotides regularly formed bonds with one another, which often broke because the change in energy was so low. However, certain sequences of base pairs have catalytic properties that lower the energy of their chain being created, enabling them to stay together for longer periods of time. As each chain grew longer, it attracted more matching nucleotides faster, causing chains to now form faster than they were breaking down.
  These chains have been proposed by some as the first, primitive forms of life. In an RNA world, different sets of RNA strands would have had different replication outputs, which would have increased or decreased their frequency in the population, i.e. natural selection. As the fittest sets of RNA molecules expanded their numbers, novel catalytic properties added by mutation, which benefitted their persistence and expansion, could accumulate in the population. Such an autocatalytic set of ribozymes, capable of self replication in about an hour, has been identified. It was produced by molecular competition (in vitro evolution) of candidate enzyme mixtures.
  Competition between RNA may have favored the emergence of cooperation between different RNA chains, opening the way for the formation of the first protocell. Eventually, RNA chains developed with catalytic properties that help amino acids bind together (a process called peptide-bonding). These amino acids could then assist with RNA synthesis, giving those RNA chains that could serve as ribozymes the selective advantage. The ability to catalyze one step in protein synthesis, aminoacylation of RNA, has been demonstrated in a short (five-nucleotide) segment of RNA.
  In March 2015, NASA scientists reported that, for the first time, complex DNA and RNA organic compounds of life, including uracil, cytosine, and thymine, have been formed in the laboratory under conditions found only in outer space, using starting chemicals, like pyrimidine, found in meteorites. Pyrimidine, like polycyclic aromatic hydrocarbons (PAHs), may have been formed in giant red stars or in interstellar dust and gas clouds, according to the scientists.
  In 2018, researchers at Georgia Institute of Technology identified three molecular candidates for the bases that might have formed an earliest version of proto-RNA: barbituric acid, melamine, and 2,4,6-triaminopyrimidine (TAP). These three molecules are simpler versions of the four bases in current RNA, which could have been present in larger amounts and could still be forward-compatibile with them, but may have been discarded by evolution in exchange for more optimal base pairs. Specifically, TAP can form nucleotides with a large range of sugars. Both TAP and melamine base pair with barbituric acid. All three spontaneously form nucleotides with ribose.
caption: A schematic representation of the RNA world hypothesis
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