86 J. IIKRHKHT TA-^'LOR 



Ilowfwr, to date it has not been pos.-ihic to test this hypothesis directly 

 hy means of hihelin'j:; these I'athci' >iii;ill chroiiiosoines. 



li. .\n)i.i:(rLAK lkvel 



The exchanges seen at the h'xcl (if the chromosome would not he 

 detectable at the molecular le^-el 1).\" any means now known. For example 

 if the chromosoinc wei'c a tandcmly liiikc(| sci'jcs of DXA particles with 

 molecular weii^hts of 10-20 X 10'', a single large cliromosome would con- 

 tain more than 100,000 of these particles. Therefore, one or two exchanges 

 per chi'omosome per i'ej)lication cycle even if all exchanges involved 

 breakage of the DXA would not be detectable at the molecular level. 

 One must conclude that the chromosom(> is comi)Osed of two remai'kably 

 stable structural units. This stability may l)e more ai)parent than real 

 because the chromosonu' may have higher orders of structural organiza- 

 tion and repair mechanisms to mend breaks (see Section VII). In any 

 case, the DXA of bacteriophages appears to be considerably less stable 

 in linear organization during transmission. Kozinski (1961) has reported 

 a dispersion of labeled phage T4 DXA that would indicate much more 

 frequent breakage than appears to occur in large chromosomes (see 

 Chapter III for further details). The two subunits of phage T7 appear 

 to be much more stable in their linear organization. Most of the subunits 

 remain intact through several replications and Meselson (1960) could 

 demonstrate that the distribution of DXA was semi-conservative. Phage 

 A also undergoes exchange rather infrequently compared to phage T4. 

 Replication has been shown to be semi-conservative, but exchanges occur 

 often enough to be detectable by density-labeling experiments (Meselson 

 and Weiglc, 1961; Kellenberger et nl.. 1961). 



Meselson and Weigle (1961) used the hea\y isotopes of nitrogen and 

 carbon to label one parent. In crosses of these with phages containing 

 the light isotopes and appropriate genetic markers, exchange could be 

 shown even between phage chromosomes which did not undergo replica- 

 tion. At low multiplicity of infection (0.1 phage/cell) the original DX^A 

 was distributed to progeny phage pai'ticles as predicted if the original 

 "phage chromosome" was composed of two subunits of DX^A and at 

 the first replication one heaAy subunit was contributed to each new 

 chromosome. These phage chromosomes of hybrid density were not 

 dispersed by exchange during the subsequent replications enough to 

 obscure the essential semi-conser\-ativ(> distribution. However, an actual 

 breakage and exchange even of non-replicating "phage chromosomes" 

 could be demonstrated at a high multiplicity of infection (5-7 ])hage/ 

 cell) with appropi-iate genetic markers. Phage were also recovered which 



