may be as simple as the substitution of a single amino acid by another and 

 may lead to profound secondary changes in protein structure and properties 

 has recently been strongly indicated by the work of Ingram on hemoglobin (32). 

 It seems inevitable that induced mutant strains of microorganisms will play 

 a most important part in providing material for the further examination of 

 these problems. 



A second consequence of the postulated relationship stems from the con- 

 cept that the genetic constitution defines the potentialities of the cell, the time 

 and degree of expression of which are to a certain extent modifiable by the 

 cellular environment. The analysis of this type of secondary control at the 

 biochemical level is one of the important and exciting new areas of biochemistry. 

 This deals with the regulation and integration of biochemical reactions by 

 means of feed-back mechanisms restricting the synthesis or activities of en- 

 zymes (33 — 36) and through substrate induced biosynthesis of enzymes (37). 

 It seems probable that some gene mutations may affect biochemical activities 

 at this level, (modifiers, and suppressors) and that chemical mutants will 

 prove of great value in the analysis of the details of such control mechanisms. 



An equally fascinating newer area of genetics, opened by Benzer (38) with 

 bacteriophage, is that of the detailed correlation of fine structure of the gene 

 in terms of mutation and recombination, with its fine structure in terms of 

 activity. Biochemical mutants of microorganisms have recently opened this 

 area to investigation at two levels of organization of genetic material. The 

 higher level relates to the genetic linkage of non-allelic genes concerned with 

 sequential biosynthetic reactions. This has been shown by Demerec and by 

 Hartmann in the biosynthesis of tryptophan and histidine by Salmonella 



(39)- 



At a finer level of organization of genetic material, the biological versatility 



of Neurospora in forming heterocaryotic cells has permitted the demonstration 

 (40 — 42) that genes damaged by mutation in different areas, within the same 

 locus and controlling the same enzyme, complement each other in a hetero- 

 caryon in such a way that synthesis of enzymatically active protein is restored, 

 perhaps, in a manner analogous to the reconstitution of ribonuclease from its 

 a and b constituents, by the production in the cytoplasm of an active protein 

 from two gene products defective in different areas. This phenomenon of 

 complementation, which appears also to take place in Aspergillus (43), permits 

 the mapping of genetic fine structure in terms of function, and should lead 

 to further information on the mechanism of enzyme production and clarifica- 

 tion of the role of the gene in enzyme synthesis. 



s-93 



