GENETIC CONTROL OF ENZYME STRUCTURE 5 



present in the specific DNA segment or gene. When all the amino 

 acids are present in the proper sequence, synthesis can then proceed. 

 Hence, in theorv, these are the events leading from a gene to a 

 specific protein. In view of the complexities of genetic effects, it is 

 remarkable that a reasonably clear-cut, though perhaps naive, picture 

 of the relationship between gene and enzyme is available. If the 

 DNA nucleotide sequence is responsible for the proper sequence of 

 amino acids in a protein, then events (mutations) which exchange, 

 delete, or add nucleotides in DNA might be expected to cause the 

 formation of altered proteins. Such altered proteins could differ 

 from the normal molecule in phvsical, chemical, or catalytic prop- 

 erties (Horowitz, 1956; Fincham, 1959; Yanofsky and St. Lawrence, 

 1960) and even in amino acid sequence. From studies on the 

 human hemoglobins (Ingram, 1958; Singer and Itano, 1959), 

 on several microbial enzymes (Yanofskv and St. Lawrence, 1960; 

 Garen, 1960 ) and on certain viral proteins ( Dreyer and Streisinger, 

 1960), it appears that mutations may in fact cause amino acid 

 substitutions in a protein. These amino acid substitutions may in 

 turn result in a change in the secondary and tertiarv structure of 

 the protein, by this means affecting the properties of the protein 

 molecule. 



Generally, two types of nucleotide substitution mutations have 

 been considered ( Crick, 1959 ) : ( 1 ) a "mis-sense" type, which re- 

 sults in the specification of a wrong amino acid and (2) a "non- 

 sense" type, in which no amino acid is specified. In the "mis-sense" 

 type, an altered protein would be formed, while in the "non-sense" 

 type, since no information is provided for one of the "linking" amino 

 acids, no protein or perhaps only fragments of a protein would be 

 formed. Attempts to detect both categories of mutational effects at 

 the protein and amino acid level would seem to be essential for an 

 understanding of mutation and the DNA-coding problem. 



At present, the approaches to the study of mutational effects on 

 proteins are in a somewhat more advanced state than analogous 

 studies with DNA. However, there are many promising approaches 

 to the problem of "decoding" DNA including studies on "incorpora- 

 tion" and "replication" mistakes using base analogs (Benzer and 

 Freese, 1958; Freese, 1959), enzymatic degradation of DNA and 

 RNA and separation of oligonucleotides (Lehman, 1960), and the 

 use of antibody prepared against different types of DNA (Levine 

 et al, I960; Thomas, Mobley, and Suskind, 1961). 



