Biophysik 7, 25--28 (1970) �9 by Storinger-Verlag 1970

A New Hypothesis on the Evolution of the Genetic Code

~ERt:~&RD ~/~ELCHER

Service de Bigehimie, D@artement de Biologic, Centre d' Etudes Nucl6aires de Saclay, B. P. No. 2, 91 - - Gif-sur-Yvette, France

and Institut fiir Mikrobiologie und Biochemisehe Technologic der Technischen I-Iochschule Wien, Getreidemark~ 9, Wien 6, Austria

Received March 12, 1970

Summary. Starting from the assumption that specific steric and energetic interactions be- tween amino acids and their respective anticodons could exist, the evolution of the genetic code is deduced from purely chemical and physical reasons. In this model the amino acids are intercalated between the two first anticodon bases and their carbon bound hydrogen atoms are assumed to penetrate into the electron clouds of the bases. By these means a gain in energy and a fixation of the amino acid is obtained in such a way that the anticodon nucleotides could be determinant for the nature of the amino acids.

The reac t ion of amino acids wi th t - R N A ' s in conjunc t ion wi th the p roper aminoaey l syn the tases exhib i t s a nea r ly absolu te speeifi ty. I f is eonceiveable t h a t the i n t e r p l a y be tween t - R N A and the syn the t a se resul t ing in the presen t expres- sion of charge speeif ify emerged dur ing the course of evolu t ion from a p r imi t ive s ta te where h igh ly specified syn the tases d id not exist . Accord ing ly the basis for t - R N A specif i ty t owards amino acids could have been de t e rmined b y in te rac t ions be tween the nucleic acids and amino acids. I t is possible t h a t the t e r t i a r y s t ruc ture of t - R N A still conta ins remains of these p r imi t ive in terac t ions .

I n a previous pape r on the t e r t i a r y s t ruc ture of t - R N A [3] i t was envisaged t h a t aminoaey la f ion of t - I~NA would t ake place in the presence and in in te rac t ion wi th the ant icodonbases . More exac t model bui ld ing s tudies showed t h a t the amino acid could be s i t ua t ed be tween the first two an t i codon bases and i t was suspected t h a t the de t e rmina t i on of the amino ac id m a y t ake place herewith. S ta r t ing wi th th is hypothes i s the following t en poin ts were found which might de te rmine the energet ic and ster ic basis of in te rac t ion be tween amino acids and nucleic acids:

1. The amino ac id is i n t e rca l a t ed be tween the first two an t i eodon bases (read f rom 3' to 5').

2. The carbon bound hyd rogen a toms of the amino acid are pene t r a t i ng in the annu l a r 7~-electron clouds of the bases. Through this a r r angemen t a s tereochemical f ixat ion of the amino acid as well as a gain in energy is ob t a ined [2].

3. The amino group of the a c t i v a t e d amino ac id will be poss ib ly bound to the n i t rogens of the a roma t i c base r ings or to the amino groups of the bases.

4. I f the t h i rd an t i eodon base is needed for the de te rmina t ion , this base could be s i tua ted over the two first ones and thus de te rmine the s ter ie and/or energet ie in te rac t ion condi t ions for fur ther hydrogen a toms of the amino acid.

26 G. Melcher:

5. I f three determined anticodon bases are needed for the code interaction, as in the case of methionine and tryptophane, it may be possible that these bases form hydrogen bonds among each other and thus form a solid cage; a possibility that exists already for point 4.

6. The Ott and SK groups of serine, threonine and eysteine could form hydro- gen bonds with the 2 'Ot I group of the central anticodon nucleotide.

7. In the case of aromatic amino acids the 2' hydrogen (not of the 2'OH) of the central anticodon nucleotide could penetrate in the 7~-electron system of the aro- matic side chain.

8. The para Ott group of tyrosine can interact with the 2'OI~I group of the third nucleotide. In this case the third anticodon nucleotide would be situated across the two first ones. In phenylalanine-t-RNA from yeast and wheat germs this 2 '0 t{ group is methylated [5].

9. The terminal amino groups of lysine and arginine can bind to the 3' phos- phate group of the central anticodon nucleotide. Arginine can eventually interact with N 7 of guanosine, the first anticodon nucleotide.

i0. Sterieally the amide groups of glutamine and asparagine can also interact with the phosphate group between the two first anticodon bases, while the all- carbonic acids will probably need magnesium ions for this purpose.

In Figs. I to 4 is shown one of the sterically possible arrangements for 4 of the amino acids and their corresponding anticodon bases [l].

For the evolution of the code in today 's form one has to consider apart the energetic interactions the evolution of the living system. This could have happened in the following way: After the abiotic synthesis of the primitive constituents -- practically any mixture of substances is possible - - polymers with protein or nucleic acid character developed [4]. This primitive nucleic acids which possibly contained different sugars, bases and acids in any sterical conformation and connection were able to interact with certain compounds like amino acids. (It should be noted tha t the class of amino acids did certainly not contain only those known today.) The composition and concentration of the prebiotic reaction mixture were determinant for these interactions and therefore for the evolution of the genetic code from the thermodynamical standpoint of view. Through the connection of the amino acids which had been arranged according to the template a peptide sequence could have been formed by intervention of a spontaneously formed enzyme.

Once this peptide or these peptides determined by the template had acquired the property to form peptide bonds and/or to copy and multiply the template one had arrived at a self-reduplicating system.

From these suggested interactions the code could have been founded, but it also will have been influenced through further evolution. In the prebiotic reaction mixture substances probably were present which were very strongly or weakly bound to the primitive nucleic acids. The first group will have had blocking and thus lethal effects while the later will have had no effects at all. Because of in- creasing stereochemical and thermodynamic constraints this influence will have been stronger working the higher developed an organism was. I t has therefore to be concluded that in today 's code exist only amino acid - - antieodon pairs in

Hypothesis on the Evolution of the Genetic Code 27

Fig. I Fig. 2

Fig. 3 Fig. 4

Figs. I to 4 show one possible arrangement for each of the following amino acids with their anticodon bases: t proline, 2 lcueine, 3 tyrosine, 4 mcthionine

equi l ibr ium to each o ther the b inding affinities of which will be i n t e rmed ia ry and of abou t the same order of magni tude .

The evolu t ion of organisms would thus be solely de t e rmined b y the fundamen- t a l laws of chemis t ry and physics and consist in changes (mutat ions) and a d a p t a t i o n s (regulations) b y ex te rna l subs tance and energy pa rame te r s which p l a y upon the l iving system.

Acknowledge~r~ents. This work was partially supported by a special fellowship of the Com- missariat s l'Enorgie Atomique and a Joliet-Curie fellowship. The author is particularly grate- ful to Dr. P. Fromageot and Dr. W. Guschlbauer for extensive discussions. Prof. Dr. 1~. Brunner and Dr. M. gShr gave also much encouragement to this work.

References 1. Crick, F. H. C.: The genetic code: yesterday, today, tomorrow. Cold Spr. ttarb. Syrup.

quant. Biol. 31, I (1966).

28 G. Meleher: Hypothesis on the Evolution of the Genetic Code

2. Hartmann, It., Strehl, F. : To be published in Theor. Chim. Aeta. 3. Meleher, G.: On tile tertiary structure of t-RNA. FEBS-Letters ], I85 (1969). 4. Ponnamperuma, C., Gabel, N. W. : Current status of chemical studies on the origin of life.

Space Life Sienees 1, 6~ (1968). 5. Zachau, H. G. : Transfer ribonucleic acids. Angew. Chemic (Int. Ed.) 8, 71t (1969).

Dr. G. Melcher Service de Biochimie, :Bat. t42 D6partement de Biologic Centre d 'Etudes Nuel6aires de Saelay, B. P. No. 2 F-9i Gif-sur-Yvette, France