222 A. GAREN AND L. M. KOZLOFF 



only at one specific position in the Iv^ strain. A striking feature of ht muta- 

 tions is their cumulative effect on the rate of attachment to B/2. For example, 

 starting with an A+ strain which is incapable of attaching to B/2, a single 

 ht mutation enables attachment to occur at a slow rate, and an accumulation 

 of two or three different ht mutations increases the rate to the maximum 

 value obtained with an h strain. Thus, the attachment properties achieved 

 in a single mutational step from h^ to h can be approached in several addi- 

 tive steps via ht mutations. In addition to the effects of ht mutations on /i+ 

 strains, the presence of these mutations in an A strain extends the host range. 

 For example, B/2/A is resistant to T2A (see Table II) but is sensitive to an h 

 strain which also harbors ht mutations (Baylor et ah, 1957). Host-range 

 mutants which appear to be similar to the ht mutants of T2 have been found 

 with T3 (Fraser and Dulbecco, 1953). 



It becomes evident from the preceding discussion that the attachment 

 specificity of a phage is under the control of a highly complex pattern of 

 genetic factors. This system offers the intriguing problem of elucidating the 

 chemical and morphological bases of the phenotypic variations resulting 

 from host-range mutations, many of which must be exceedingly subtle. 



C. Genetic Control of Tryptophan Requirement 



The unique requirement of certain strains of the T-even phages for 

 L-tryptophan as a cofactor for attachment (see Section V, D) has been sub- 

 jected to a genetic analysis (Brenner, 1957). In pairwise crosses between in- 

 dependently isolated tryptophan-requiring strains of T4 (called c), trypto- 

 phan-independent recombinants (c+) were produced, showing that mutations 

 to c can arise at different positions on the chromosome of a c"*" stram. The c 

 mutations studied were found to be closely linked, and in this respect are 

 similar to the host-range h'^ mutations which also cluster within a single 

 region of the chromosome (separated from the region of the c mutations). 

 The effect of c mutations probably is on the arrangement of the tail fibers 

 (see Section V, D); this effect may differ among different mutants, as indi- 

 cated by the requirement for calcium ions, in addition to tryptophan, with 

 some of the mutants, and by the temperature-dependence of the tryptophan 

 requirement with other mutants (Delbriick, 1948; Brenner, 1957). Thus, the 

 genetic and phenotypic properties required by the T-even phages to achieve 

 tryptophan independence appear to be quite specific, since the transformation 

 from independence to dependence can occur in various ways as a result of 

 different c mutations. 



D. Phenotypic Mixing 



The host-range properties of some of the progeny formed in crosses 

 between a T2 and a T4 parent are unusual for two reasons. First, as was 



