Regulation of Gene Action — Operons 



461 



the normal regulatory factors for leucine ap- 

 ply demonstrating that the normal leucine 

 regulator gene is still present. It is hypoth- 

 esized that normally su leu 500 is a regu- 

 lator gene for one or more other operons. 

 When the leucine operon is o + , the sup- 

 pressor substance made by su leu 500 has 

 no effect on the operon. The mutation to 

 o' makes the leucine operon susceptible to 

 the foreign repressor produced by su leu 

 500, the repressor acting here as a super- 

 repressor. Mutation at the su leu 500 locus 

 partially restores the susceptibility of o' to 

 its own repressor and, it is inferred, also 

 permits the operons normally regulated by 

 su leu 500 to act constitutively. 



The mutant o r first appeared in a culture 

 treated with 5-bromo uracil. Its pattern of 

 reverse mutation by 2-aminopurine strongly 

 suggests that the production of o T involved 

 the transition of a single base-pair. Induc- 

 tion of mutations in su leu 500 by 2-amino- 

 purine indicates that simple base alterations 

 may result in a change in the nature of the 

 su leu 500 repressor so that o T is no longer 

 repressed by it. These conclusions lead us 

 to believe that: 



1. Regulator genes for different operons 

 differ from one another by relatively 

 few nucleotides in the region that spec- 

 ifies their repressor's action upon an 

 operator 



2. Operator genes for different operons 

 differ from one another by relatively 

 few nucleotides. 



Operons (such as Lac) whose gene prod- 

 ucts are proteins needed for special diges- 

 tive or catabolic reactions, or for special 

 structural or other biological purposes, are 

 often normally repressed by repressor sub- 

 stances produced by regulator genes. To 

 function, such operons must be derepressed. 

 Other operons, however — particularly those 

 whose enzyme products are used more rou- 

 tinely in metabolism, especially in synthetic 



or anabolic reactions — apparently are not 

 ordinarily repressed but are functional. In 

 such cases regulation of operon function is 

 sometimes accomplished by a repressor pro- 

 duced when the end product of operon ac- 

 tion combines with the gene product of a 

 regulator gene. Other mechanisms of con- 

 trolling operon action via feedback systems 

 have been suggested. 



At the level of the gene, we see that any 

 structural gene in an operon can be perma- 

 nently "turned off" by mutations within it. 

 In such a gene, deletions which do not in- 

 volve three or groups of three nucleotides 

 are also expected to turn off other structural 

 genes in the operon whose translation on the 

 ribosome occurs later. We have seen that 

 the functioning of an entire operon can be 

 regulated or changed by the alleles present 

 at the operator locus or at normal and for- 

 eign regulator loci. In principle, such 

 operon regulation could occur either at its 

 transcription or translation stage. For ex- 

 ample, a DNA base substitution at the end 

 where messenger RNA synthesis starts might 

 cause that end to be susceptible to its own 

 or another repressor substance and prevent 

 transcription. A deletion which does not 

 comprise a multiple of three nucleotides 

 might occur at the end of the operon whose 

 messenger RNA sequence is translated first. 

 In this instance, the messenger RNA would 

 be produced but would make complete non- 

 sense. After normal messenger RNA is 

 formed the operon might also be turned off 

 by digestion of the messenger, by a suppres- 

 sor which blocks translation of the mes- 

 senger, 4 or by failure of the translated pro- 

 teins to be liberated from the ribosome. 

 Intraoperon regulation can occur at the 

 translation stage, 5 since different proteins 



4 See E. Orias and T. K. Gartner (1964). 

 ■^See Y. Ohtaka and S. Spiegelman (1963). B. N. 

 Ames and P. E. Hart man (1964). and the refer- 

 ences to R. Byrne, et al. ( 1964) on p. 432, and to 

 M. Nirenberg and P. Leder (1964) on p. 446. 



