A Novel Theory on the Origin of the Genetic Code: A GNC-SNS Hypothesis

Abstract

We have previously proposed an SNS hypothesis on the origin of the genetic code (Ikehara and Yoshida 1998). The hypothesis predicts that the universal genetic code originated from the SNS code composed of 16 codons and 10 amino acids (S and N mean G or C and either of four bases, respectively). But, it must have been very difficult to create the SNS code at one stroke in the beginning. Therefore, we searched for a simpler code than the SNS code, which could still encode water-soluble globular proteins with appropriate three-dimensional structures at a high probability using four conditions for globular protein formation (hydropathy, alpha-helix, beta-sheet, and beta-turn formations). Four amino acids (Gly [G], Ala [A], Asp [D], and Val [V]) encoded by the GNC code satisfied the four structural conditions well, but other codes in rows and columns in the universal genetic code table do not, except for the GNG code, a slightly modified form of the GNC code. Three three-amino acid systems ([D], Leu and Tyr; [D], Tyr and Met; Glu, Pro and Ile) also satisfied the above four conditions. But, some amino acids in the three systems are far more complex than those encoded by the GNC code. In addition, the amino acids in the three-amino acid systems are scattered in the universal genetic code table. Thus, we concluded that the universal genetic code originated not from a three-amino acid system but from a four-amino acid system, the GNC code encoding [GADV]-proteins, as the most primitive genetic code.

DNA partitions into triplets under tension in the presence of organic cations, with sequence evolutionary age predicting the stability of the triplet phase

“…We further observe that the residues advanced by Ikehara et al (Ikehara et al 2002) as forming the minimal set for a functional proteome (marked ☥ in Table 3) are also those which partition most naturally into triplets.…”

“…Given the expected importance of sequence effects, simulations were run both with a low-entropy sequence of d [G 12 C 12 ] (encoding four glycines and four prolines) and a sequence chosen to show strong triplet disproportionation based on (Ikehara et al 2002)). DNA duplexes were stretched by an additional 100 Å from their relaxed lengths, over a time period of 150 ns, giving a stretching rate of 0·029 Å ns…”

“…In the same way as for unstretched Watson-Crick base-paired DNA structures, we remark that the structure of the Σ phase is linked to function: the partitioning of bases into codons of three base pairs each is the first phase of operation of recombinase enzymes such as RecA, facilitating alignment of homologous or near-homologous sequences. By showing that this process does not require any very sophisticated manipulation of the DNA, we position it as potentially appearing as an early step in the development of life, and correlate the postulated sequence of incorporation of amino acids (phase 0 or 'the GADV world' (Ikehara et al 2002), phase 1 or 'GADVESPLIT' (Koonin & Novozhilov, 2009;Wong, 1975Wong, , 2005, then the remaining amino acids, CMFYHRKNQ), into molecular biology with the ease of Σ-formation for sequences including the associated codons. We also note that the machinery of nucleotide to peptide translation occurs necessarily with reference to triplets of bases, so that further investigation into the Σ phase of single and double strands of RNA and DNA might be a valuable source of insight into the origins not only of recombination, but also of gene expression.…”

Perspectives in Glycomics and Lectin Engineering

“…A -alanine, V -valine, D -aspartic acid) could be the original genetic code (101)(102)(103)(104)(105).…”

Catalysis in the Primordial World

“…In line with this research is the [GADV]-protein world hypothesis, 34 stating that the first biological molecules were proteins composed of only four amino acids: glycine (G), alanine (A), aspartic acid (D), and valine (V). In the repeated heat-drying experiments (mimicking processes on primitive Earth) of aqueous solutions of the respective amino acids in equimolar concentrations, a library of random peptides were synthesized, which showed catalytic abilities to hydrolyze β-galactoside and amide (peptide) bond.…”