The Combinatorial Fusion Cascade to Generate the Standard Genetic Code

Combinatorial fusion cascade was proposed as a transition stage between prebiotic chemistry and early forms of life. The combinatorial fusion cascade consists of three stages: eight initial complimentary pairs of amino acids, four protocodes, and the standard genetic code. The initial complimentary pairs and the protocodes are divided into dominant and recessive entities. The transitions between these stages obey the same combinatorial fusion rules for all amino acids. The combinatorial fusion cascade mathematically describes the codon assignments in the standard genetic code. It explains the availability of amino acids with the even and odd numbers of codons, the appearance of stop codons, inclusion of novel canonical amino acids, exceptional high numbers of codons for amino acids arginine, leucine, and serine, and the temporal order of amino acid inclusion into the genetic code. The temporal order of amino acids within the cascade is congruent with the consensus temporal order previously derived from the similarities between the available hypotheses. The control over the combinatorial fusion cascades would open the road for a novel technology to develop artificial microorganisms.

Combinatorial Fusion Rules to Describe Codon Assignment in the Standard Genetic Code

We propose combinatorial fusion rules that describe the codon assignment in the standard genetic code simply and uniformly for all canonical amino acids. These rules become obvious if the origin of the standard genetic code is considered as a result of a fusion of four protocodes: Two dominant AU and GC protocodes and two recessive AU and GC protocodes. The biochemical meaning of the fusion rules consists of retaining the complementarity between cognate codons of the small hydrophobic amino acids and large charged or polar amino acids within the protocodes. The proto tRNAs were assembled in form of two kissing hairpins with 9-base and 10-base loops in the case of dominant protocodes and two 9-base loops in the case of recessive protocodes. The fusion rules reveal the connection between the stop codons, the non-canonical amino acids, pyrrolysine and selenocysteine, and deviations in the translation of mitochondria. Using fusion rules, we predicted the existence of additional amino acids that are essential for the development of the standard genetic code. The validity of the proposed partition of the genetic code into dominant and recessive protocodes is considered referring to state-of-the-art hypotheses. The formation of two aminoacyl-tRNA synthetase classes is compatible with four-protocode partition.