Chapter *41 



REGULATION OF GENE ACTION- 

 GROWTH, DIFFERENTIATION, 

 AND DEVELOPMENT 



T 



|he six preceding chapters dealt 

 with the regulation of gene 

 synthesis and action. The 

 aim of this chapter is to show how genetic 

 systems of the types already discussed are 

 or may be involved in the regulation of 

 growth, differentiation, and development. 



Phage T4 Morphogenesis 1 



The genome of </>T4 carries the information 

 for the production of several proteins (noted 

 in Chapter 35). Some mutants of protein- 

 specifying genes can direct the synthesis of 

 an altered protein. Some of these altered 

 proteins function as well, or nearly as well, 

 as the unaltered wild-type proteins in hosts 

 grown at normal temperatures (about 25 °C) 

 but become inactive in hosts grown at higher 

 temperatures (about 40°C). Two types of 

 such temperature-sensitive , ts, mutants have 

 been found for deoxycytidylate hydroxy- 

 methylase, dHMCase (Figure 35-1 and 

 p. 451). Although both show reduced 

 dHMCase activity at low temperatures as 

 compared with the wild-type enzyme, their 

 response to a shift (from normal to high) 

 in the temperature at which the infected host 

 is grown is different. In one type of mutant, 

 the altered enzyme is inactivated by heat 

 denaturation at any time during the eclipse 



1 The following account is based largely upon the 

 work of R. S. Edgar, M. Susman. G. H. Denhardt. 

 L. Boice, and co-workers. See R. H. Epstein. 

 et al. (1964). 

 501 



period in which the temperature shift is 

 made; the other type of mutant produces 

 an altered dHMCase inactivated only if the 

 temperature shift is made before the first 

 third of the eclipse period and resistant to 

 shifts made later. These results suggest that 

 the former type of enzyme can be denatured 

 by heat after it is synthesized; that the latter 

 type is temperature-sensitive only during its 

 synthesis. 



It has been found that the ts mutants — 

 really conditional lethals — occur in roughly 

 half of all phage genes. The loci of these 

 genes have been mapped, and their pheno- 

 typic effects studied at chemical, physio- 

 logical, and morphological levels. The re- 

 sults are summarized in Figure 26-4 (p. 

 343). We see that the circular phage ge- 

 nome is organized into blocks containing 

 genes with common functions. These blocks 

 include the following: 



Mutants 

 DO 



Common Characteristics 



DA 



Cannot initiate DNA synthesis 

 (hence, normal alleles initiate 

 DNA synthesis) 

 Start DNA synthesis, but cease 

 after a short time 

 DD Delay DNA synthesis 



"tail fiber" Form (otherwise normal) particles 



lacking tail fibers 

 "head" Form particles with heads missing 

 (free tails are present in lysates) 

 tail' Form particles with tails missing 



or incomplete 



"tail 



These results strongly suggest that the 

 genes in any block function at the same or 

 nearly the same time, and that the sequence 

 of different blocks of genes may reflect the 

 sequence of events in phage replication and 

 maturation. The thymidylate synthetase 

 (p. 449) locus is apparently an exception 

 to this sequence - since it is located well 

 within the tail fiber region rather than in the 



'-' According to E. H. Simon and I. Tessman 

 (1963). 



