402 MAHLON B. HOAGLAND 



the correct sequence of bases on transfer RNA for it is able to deposit its 

 amino acid on only one kind of transfer RNA molecule. Thus the a priori 

 argument for the adaptor hypothesis loses some of its impact. But an im- 

 portant feature of an adaptor would be its ability chemically to bind an 

 amino acid in such a way as to maintain it in a reasonably stable, and yet 

 a still activated state. The most likely candidate for a molecule with "a 

 specific hydrogen-bonding surface," the adaptor, would of course, as Crick 

 suggested, be one containing nucleotides. 230 An oligoribonucleotide itself 

 would serve ideally as such an adaptor, having both acylatable groups for 

 amino acid attachment, and at the same time a specific pattern of hydro- 

 gen bonds (a specific base sequence) which could react directly with a 

 complementary sequence on the RNA template. Such base pairing would 

 be in all respects analogous to that found in DNA and to that most likely 

 existing in RNA. Such hydrogen-bonding interaction between bases in a 

 polynucleotide would have the specificity demanded by what is known 

 thus far about protein structure. 



The adaptor hypothesis may be stated explicitly as follows: "Amino 

 acids, before entering the ribonucleoprotein particles first react with small 

 polynucleotide molecules. These adaptor molecules accompany the amino 

 acids into the particles and are responsible for properly locating them on 

 the particle RNA. This is accomplished by pairing of the adaptors' bases 

 with complementary base sequences on the particle RNA. Having com- 

 pleted their mission the adaptors then return to the soluble milieu. 231 " 



This new concept has important qualitative differences from earlier sug- 

 gested mechanisms of amino acid-template interaction. It predicts: (1) 

 that each amino acid must initially be attached to an oligonucleotide, and 

 each of these oligonucleotides will be specific for a particular amino acid. 

 (2) As a consequence of this first prediction, separate enzymes would be 

 necessary to attach each amino acid to its specific adaptor. One could hardly 

 visualize a single enzyme being capable of distinguishing between twenty 

 different oligonucleotides. (3) It predicts that the amino acid would arrive 

 at the template in company with this nucleotide component. This means 

 that the amino acid would be found transiently associated with ribosomal 

 RNA before it appears in protein. (4) It implies that the amino acid need 

 never have any direct chemical contact with the template — that the adap- 

 tor alone makes the contact with the specific site on the template. The 

 amino acid might of course then be transferred to the template itself but 

 this step is not a requirement of the theory. At any rate the mechanism by 

 which the amino acid is brought to the proper locus on the template does 

 not require that the template ever "see" the amino acid. (5) The theory 



230 F. H. C. Crick, Biochem. Soc. Symposia 14, 25 (1957). 



231 M. B. Hoagland, Brookhaven Symposia in Biol. 12, 40 (1959). 



