10 MOLECULES, VIRUSES, AND BACTERIA 



ends and works toward the middle (without necessarily asking ques- 

 tions about mechanism); the latter works in the opposite direction. 

 Recent discoveries resulting from the study of protein synthetic mecha- 

 nisms, concerning the role of RNA in protein synthesis, have helped 

 to bring workers in these two areas of research much closer together. 

 I would like to discuss these findings briefly today. 



Let me first make some statements about protein synthesis which 

 will serve to orient us. Substantiation for them may be found in the 

 many reviews on the subject that have recently appeared. Particularly 

 pertinent are the articles of Crick ( 1958 ) , Chantrenne ( 1958 ) , Zamec- 

 nik ( 1959 ) , Gros ( 1960 ); and Hoagland ( 1960 ) . 



Kinetic studies in whole cells and in subcellular systems of both 

 microbial and mammalian origin appear clearly to establish that amino 

 acids appear first in peptide linkage in close association with the 

 ubiquitous cellular particles, the ribosomes. Protein synthesized by 

 ribosomes appears to be quickly removed to supply the cells' needs and 

 free the synthetic site for further synthesis. 



Ribosomes consist almost entirely of protein and RNA in equal 

 amounts and have a molecular weight of the order of 4,000,000. Mag- 

 nesium ions and, to a lesser extent, calcium ions are important to the 

 maintenance of the structural integrity of these bodies, and in their 

 absence the ribosomes dissociate to smaller subunits. The physiological 

 significance of ribosomal dissociation is unknown, but even in the sub- 

 units the RNA is relatively highly polymerized (perhaps of molecular 

 weight 500,000). The bulk of ribosomal protein is not that in process 

 of synthesis, and hence it is thought to serve to maintain in some way 

 the structure of the particle. 



Ribosomes may carry out protein synthesis in the absence of a 

 direct influence of DNA. This is borne out by studies on enucleated 

 cells (cf. the review by Chantrenne, 1958). Ribosomal RNA and pre- 

 sumably the ribosome itself is metabolically a relatively stable cellular 

 component, at least in certain rapidly growing cells (Scott and Taft, 

 1958), and, once made, it apparently is autonomous in supplying in- 

 formation for protein synthesis. Since DNA is the ultimate molecular 

 repository of an organism's genetic constitution, information from DNA 

 must in some way be supplied to the ribosomes. The most widely ac- 

 cepted current working hypothesis is that the linear order of the four 

 nucleotide units of DNA in some way determines the linear order of 

 the four nucleotide units of ribosomal RNA, which in turn specifies the 

 linear order of the 20 amino acids in protein. It is implicit in this theory 

 that the amino-acid sequence in a protein, i.e., its primary structure, 

 is the key determinant of the protein's genetic specificity. The simplest 

 mechanism for bringing about this passage of information from DNA 



