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The simplest possible informational heteropolymer requires only a two-letteralphabet to be able to store information. The evolutionary choice of fourmonomers in the informational biomolecules RNA/DNA or their progenitors isintriguing, given the inherent difficulties in the simultaneous and localizedprebiotic synthesis of all four monomers of progenitors of DNA from commonprecursors on early Earth. Excluding the scenario where a two-letter alphabetgenome eventually expanded to include two more letters to code for more aminoacids on teleological grounds, we show here that a heteropolymer sequence inthe RNA-world-like scenario would have had to be composed of at least fourletters in order to predictably fold into a specific secondary structure, andhence must have outcompeted the two-letter alphabet genomes. Using a model thatwe previously used to demonstrate the evolutionary advantages of unidirectionalreplication and anti-parallel strand orientation of duplex DNA, we show herethat the competing constraints of maximum replicative potential and predictablesecondary structure formation can be simultaneously satisfied only bypalindromic heteropolymer sequences composed of a minimum of four letters,within the premise of the presence of sequence-dependent asymmetriccooperativity in these RNA/DNA progenitors.

Joint optimization of replication potential and information storage set the letter size of primordial genetic alphabet