X. TMV STUDIES IN GENETIC CODING 479 



Tobacco mosaic \'iru.s (TMV) was the virus first to be discovered, 

 first to be isolated, and fii-st to be degraded into protein and infective 

 RNA, and to be reconstituted from these components. Because so much 

 more is known about this than most other viruses, this article will be 

 largely devoted to TMV. We shall first discuss the ])rinciple features of 

 the structure and function of the tobacco mosaic virus, and we shall 

 then attempt to show in what manner the study of this virus has con- 

 tributed and may continue to contribute to our understanding of the 

 molecular aspects of genetics. ]VIore detailed discussions of various aspects 

 of this field can be found in recent reviews (Fracnkel-Conrat and 

 Ramacliandran, 1959; Schuster, 1960; Klug and Caspar, 1960; Gierer, 

 1960). 



II. TMV-Protein 



A. ROD STRUCTURE AND CHAIN CONFIGURATION 



Tobacco mosaic virus (TMV) is a rod-shaped particle (radius 150- 

 180 A, length 3000 A) composed of 5% ribonucleic acid (RNA) and 

 95% protein and having a particle weight of 40 million. The model 

 presented in Fig. 1 is largely based on data obtained through a thorough 

 X-ray diffraction analysis (Franklin and Klug, 1955, 1956; Franklin 

 et al., 1957; Klug and Caspar, 1960), particularly of a methyl mercury 

 derivative of the virus (Franklin and Holmes, 1958). As shown in the 

 figure, the rod is believed to be hollow along its axis (40 A diameter) 

 and surrounded by protein units in a gently pitched helical array (49 

 units in 3 turns, pitch 23 A). The nucleic acid is threaded through about 

 2130 protein units, thus also forming a helix of the same pitch with a 

 diameter of 80 A. This concept of the architecture of the virus particle 

 is well supported by recent improvements in electron microscopic tech- 

 niques (Nixon and Woods, 1960). Figure 2 shows such an electron 

 micrograph of TMV. 



The virus rod is disaggregated by many agents which disrupt sec- 

 ondary bonds occurring in proteins, such as heat, urea, detergents, alkali, 

 acid, phenol and acetic acid. Some of these agents supply methods for 

 the isolation of one or the other of the two components in native or 

 biologically functional state while the other component is more or less 

 degraded or denatured. Of these methods, acetic acid is the most con- 

 venient and simple for the isolation of the protein (Fraenkel-Conrat, 

 1957), and phenol for that of the RNA (Gierer and Schramm, 1956; 

 Haschemeyer et al., 1959). 



Although the minimum molecular weight of the protein component 

 is about 18,000, as shown later, the protein as usually obtaincMJ exhibits 



