The 15th Anniversary of Life—Alternatives to RNA World

Dear Colleagues,

In 1924, Alexander Oparin pioneered the scientific investigation of the origin of life. In the first half-century hence, RNA was mostly unknown and thus not considered important. Only >50 years later, upon the discovery of ribozymes, Walter Gilbert conceived the “RNA World” idea, which became extremely popular in research on the origin of life. This present Special Issue will attempt to challenge this hypothesis. A key justification for RNA World is that this polymer can self-copy its encoded chemical information, and in parallel can catalyze reactions. A prime question raised is whether RNA is unique in possessing these two properties together.

A catalyst is a compound capable of enhancing the rate of a chemical reaction. It turns out that even single amino acids can accomplish this, meaning that RNA is definitely not unique. As for information-copying, RNA indeed can under, certain conditions, copy sequences information, but is this the only way to copy information?

The fact is that contemporary life research embraces mostly a second type of information-copying, namely composition. This is exemplified by the cellular metabolome, namely the counts of every compound in a cell. It is obvious that reproducing cells requires a complex metabolic network that allows the relative amounts of all compounds (metabolites, proteins, mRNAs and lipids) to remain unchanged in a homeostatic growth process. Subsequent fission will typically lead to two very similar copies. Although mRNAs take part in this miraculous process, mRNA molecules in all cells do not self-replicate!

It is obvious that at one point in time life must have included the emergence of protocells with metabolism. Some network dynamics similar to those observed today in all living cells should, under certain circumstances, lead to protocellular self-reproduction. There is no reason to believe that this cannot happen in some primitive protocells without mRNA.  

The primitive protocells must have absorbed organic molecules from the primordial soup, guardedly constructing metabolism (“Metabolism First”). mRNA or ribozymes would not be necessary at this point, and likely appeared at much later stages, at which ribosome and long proteins would co-evolve.

The real puzzle, partially addressed, is how primordial entities that harbor catalytic networks sometimes self-reproduce. Our own model suggests that micelles and vesicles (kind of protocell precursors) benefit from the huge environmental organic repertoire, resulting in a huge variety of supramolecular entities, affording the possibility of selection. Such self-reproducing protocells may beget multiple progeny with mutations, thus leading to species that can undergo Darwinian evolution. NASA’s definition encompasses even very simple molecular ensemble with the right properties as life. RNA will consequently be formed after a long path of Darwinian evolution (see figure).

The present Special Issue aims to publish articles that portray molecular models, experimental results, or reviews, devoted to understanding how life spontaneously came into being in the soup without the necessity of RNA or other long biopolymers. 

Prof. Dr. Doron Lancet
Dr. Amit Kahana
Guest Editors

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• supramolecular
• lipid
• assembly
• protocell
• compositional
• information
• spontaneous
• catalytic
• network
• reproduction
• species
• Darwinian
• evolution
• origin
• life