VIII. PROTEIN SYNTHESIS AND GENE ACTION 393 



U, A, and G. Tliis is consistent with another licmoglohin where <flutaniic 

 acid is replaced by glutaininc, which is UGC. The code word for gluta- 

 mine, UGC, was predicted from TMV replacement data, but so far the 

 synthetic polynucleotide, UGC, has not stimulated glutainine incorpora- 

 tion. Smith also considered the question of sequences of the bases in 

 any code word, and it seems likely that U may only occupy two of the 

 three possible positions. Further, if the sequence of one code word con- 

 taining three bases is established, most of the others can be deduced. 

 Amino acid replacements in proteins of various species were also com- 

 pared, and here the situation was not as clear. Some of the changes must 

 involve two mutations if the code letters are correct. However, this may 

 not be too unusual. The implications of these comparisons in the evolu- 

 tion of protein structure and function are of great interest. 



One of the important conclusions from the agreement in code words 

 derived from amino acid replacements and those derived from stimula- 

 tion of amino acid incorporation is that the code is "universal." That is, 

 in general the code word for an amino acid is the same in mammals, 

 E. coli, and TMV. A similar conclusion was reached from the finding 

 that transfer RXA from various species could be used to synthesize 

 hemoglobin using reticulocyte ribosomes. This conclusion does not 

 exclude differences in composition or specificity in messenger RNA from 

 different species, but would ascribe these to non-coding portions of the 

 molecule. Nonetheless, it is still important to show that poly-U will code 

 only for phenylalanine using mammalian ribosomes," for example, or that 

 a particular messenger RNA directs the synthesis of the same protein 

 in ribosomes of two different species. 



This question is also related to the question of the role of the ribo- 

 some in protein synthesis. While ribosomes of E. coli can accept informa- 

 tion from different types of natural and synthetic messengers, only 10% 

 or less of the ribosomes contain labeled poly-U when this is used as 

 messenger. The rest of the labeled poly-U is rapidly degraded, but 

 phenylalanine incorporation continues, implicating these special ribo- 

 somes as the "active" sites of protein synthesis (Matthaei et al., 1962; 

 M. Nirenberg, private communication). Do these "active" ribosomes 

 represent a special class, or are they representative of all the ribosomes 

 of the cell? Before discussing this question, it is of interest to note that 

 these data provide evidence for a catalytic role of the messenger RNA 

 in the active ribosomes. Since one phenylalanine residue is incorporated 

 per uridylic acid residue under favorable conditions, and much of the 

 poly-U is probably never integrated into functional ribosomes, plus the 



"This result has now been reported l\v H. Arnstein {Nature, in press) and 

 confirmed in this laboratory. 



