A Note on the Evolution of Nucleic Acids 



A. E. MIRSKY 



Rockefeller Institute, New York, U.S.A. 



Large molecules such as those of proteins and nucleic acids are of importance 

 for the organization of vital processes and for their highly specific characteristics. 

 Knowledge concerning the synthesis of these molecules in the cell is now 

 developing rapidly. How these molecules first came into being ages ago is, how- 

 ever, still altogether obscure. The problem would probably be more manageable 

 if we can conceive of the origin of large molecules as occurring in stages rather 

 than as happening all at once by some rare chance. 



In this note I would Hke to present a group of observations which may 

 possibly cast some light on the evolution of nucleic acids. Recent experiments 

 have shown that small polynucleotides containing only some three or four 

 nucleotides or larger polynucleotides of simple composition can perform one 

 of the important functions that in the cell is normally accomplished by a com- 

 plex nucleic acid containing a hundred or more nucleotides. The substitution 

 within the nucleus of small or simple polynucleotides for the large complex 

 ones normally present is possible experimentally if the structural background of 

 the nucleus is maintained. A significant point about the function of nucleic 

 acid to which I am referring is that it is relatively non-specific; it concerns the 

 synthesis of adenosine triphosphate (ATP) rather than the transmission of 

 hereditary specificity. 



I must now describe the biochemical system in which it has been found that 

 polynucleotides serve as 'cofactors' for ATP synthesis. Nuclei isolated from 

 calf thymus are able under certain conditions to synthesize protein [i]. When these 

 nuclei are treated with deoxyribonuclease most of their deoxyribonucleic acid 

 (DNA) is removed and at the same time their abihty to synthesize protein is 

 greatly reduced. It is possible to 'restore' much of the DNA that has been re- 

 moved and when this happens incorporation of amino acids commences again. 

 At first the DNA restored to the nucleus was of course a carefully prepared 

 sample of calf-thymus DNA. Then it was found that DNA prepared from 

 other tissues of the calf or indeed from other organisms (from sea-urchin sperm, 

 for example) would do as well as the homologous DNA in promoting amino 

 acid uptake by the nuclei. Furthermore, the DNA molecule need not be intact, 

 for alkali-denatured DNA and the split products obtained by DNAase digestion 

 are just as effective as the original DNA preparation. Even ribonucleic acids will 

 substitute for the DNA of the thymus in restoring amino acid incorporation into 

 nuclear proteins. Finally, the lack of a specificity requirement is most conclu- 

 sively shown by experiments in which [I'CJalaninc and ["C]leucine uptakes 



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