RNA world

[13] Protein enzymes may have replaced RNA-based ribozymes as biocatalysts because the greater abundance and diversity of the monomers of which they are built makes them more versatile.

[7] One of the challenges in studying abiogenesis is that the system of reproduction and metabolism utilized by all extant life involves three distinct types of interdependent macromolecules (DNA, RNA, and proteins).

[15] In an article he contributed to a volume issued in honor of Nobel-laureate physiologist Albert Szent-Györgyi, he explained that the primitive Earth's environment could have produced RNA molecules (polynucleotide monomers) that eventually acquired enzymatic and self-replicating functions.

[16] Other mentions of RNA as a primordial molecule can be found in papers by Francis Crick[17] and Leslie Orgel,[18] as well as in Carl Woese's 1967 book The Genetic Code.

[3] One version of the hypothesis is that a different type of nucleic acid, termed pre-RNA, was the first one to emerge as a self-reproducing molecule, to be replaced by RNA only later.

On the other hand, the discovery in 2009 that activated pyrimidine ribonucleotides can be synthesized under plausible prebiotic conditions[22] suggests that it is premature to dismiss the RNA-first scenarios.

[23][24] Despite their structural simplicity and possession of properties comparable with RNA, the chemically plausible generation of "simpler" nucleic acids under prebiotic conditions has yet to be demonstrated.

The large subunit of the ribosome includes an rRNA responsible for the peptide bond-forming peptidyl transferase activity of protein synthesis.

[60] The nucleoside cytosine has a half-life in isolation of 19 days at 100 °C (212 °F) and 17,000 years in freezing water, which some argue is too short on the geologic time scale for accumulation.

[63] Pyrimidine ribonucleosides and their respective nucleotides have been prebiotically synthesised by a sequence of reactions that by-pass free sugars and assemble in a stepwise fashion by including nitrogenous and oxygenous chemistries.

In a series of publications, John Sutherland and his team at the School of Chemistry, University of Manchester, have demonstrated high yielding routes to cytidine and uridine ribonucleotides built from small 2- and 3-carbon fragments such as glycolaldehyde, glyceraldehyde or glyceraldehyde-3-phosphate, cyanamide, and cyanoacetylene.

One of the steps in this sequence allows the isolation of enantiopure ribose aminooxazoline if the enantiomeric excess of glyceraldehyde is 60% or greater, of possible interest toward biological homochirality.

Photoanomerization with UV light allows for inversion about the 1' anomeric centre to give the correct beta stereochemistry; one problem with this chemistry is the selective phosphorylation of alpha-cytidine at the 2' position.

[65] However, in 2009, they showed that the same simple building blocks allow access, via phosphate controlled nucleobase elaboration, to 2',3'-cyclic pyrimidine nucleotides directly, which are known to be able to polymerise into RNA.

[66] However, John Sutherland said that while his team's work suggests that nucleic acids played an early and central role in the origin of life, it did not necessarily support the RNA world hypothesis in the strict sense, which he described as a "restrictive, hypothetical arrangement".

[citation needed] On August 8, 2011, a report, based on NASA studies with meteorites found on Earth, was published suggesting building blocks of RNA (adenine, guanine, and related organic molecules) may have been formed in outer space.

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 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.

Pyrimidine, like polycyclic aromatic hydrocarbons (PAHs), may have been formed in red giant stars or in interstellar dust and gas clouds, according to the scientists.

[81] 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).

Additional evidence supporting the concept of an RNA world has resulted from research on viroids, the first representatives of a novel domain of "subviral pathogens".

[87][88] Viroids infect plants, where most are pathogens, and consist of short stretches of highly complementary, circular, single-stranded and non-coding RNA without a protein coat.

[89] Based on their characteristic properties, in 1989 plant biologist Theodor Diener argued that viroids are more plausible living relics of the RNA world than introns and other RNAs considered candidates at the time.

[90] Diener's hypothesis would be expanded by the research group of Ricardo Flores,[91][92] and gained a broader audience when in 2014, a New York Times science writer published a popularized version of the proposal.

Multiplicity reactivation has been reported to occur in influenza virus infections after induction of RNA damage by UV-irradiation,[100] and ionizing radiation.

[105] Steven Benner has argued that chemical conditions on the planet Mars, such as the presence of boron, molybdenum, and oxygen, may have been better for initially producing RNA molecules than those on Earth.

[112] The iron-sulfur world theory proposes that simple metabolic processes developed before genetic materials did, and these energy-producing cycles catalyzed the production of genes.

[citation needed] The relative chemical complexity of the nucleotide and the unlikelihood of it spontaneously arising, along with the limited number of combinations possible among four base forms, as well as the need for RNA polymers of some length before seeing enzymatic activity, have led some to reject the RNA world hypothesis in favor of a metabolism-first hypothesis, where the chemistry underlying cellular function arose first, along with the ability to replicate and facilitate this metabolism.

Specifically, peptide bond formation, the reaction that binds amino acids together into proteins, is now known to be catalyzed by an adenine residue in the rRNA.

Likewise, in eukaryotes the maintenance of telomeres involves copying of an RNA template that is a constituent part of the telomerase ribonucleoprotein enzyme.

A comparison of RNA ( left ) with DNA ( right ), showing the helices and nucleobases each employs
The major difference between RNA and DNA is the presence of a hydroxyl group at the 2'-position.
The RNA world hypothesis proposes that spontaneous polymerization of ribonucleotides led to the emergence of ribozymes and including an RNA replicase .