GENETIC CONTROL 35 



just as proper linear sequences of letters on a white sheet constitute written 

 language. 



C. THE COLINEARITY HYPOTHESIS 

 1. Principle 



Results reviewed in the preceding pages show that the genetic material 

 controls the nature and the position of individual amino acids in the 

 protein polypeptide chains. Since nucleic acids as well as proteins are 

 linear polymers and since nucleic acids differ from one another by the 

 arrangement of the bases just as polypeptides differ by the order of their 

 amino acids, it seems logical to assume a point to point correspondence 

 between the two linear sequences. 



To test this hypothesis directly, one might think of isolating a specified 

 protein and the corresponding piece of DNA. Determination of the com- 

 plete amino acids sequence in the protein and of the nucleotides sequence 

 in the DNA molecule would tell to what extent and in which way they 

 are correlated. 



One-half of such an experiment is feasible presently. The complete 

 sequence of amino acids has been worked out for insulin, for several 

 pituitary hormones, and for ribonuclease (Spackman et al., 1960). Partial 

 sequences are known for several other proteins. With skill and patience, the 

 structure of a polypeptide can now be resolved by the methods developed 

 by Sanger and his followers. But the other half of the experiment seems 

 hopeless. No ways are known to recognize by physicochemical means the 

 piece of DNA corresponding to a given protein and to separate it from the 

 rest of the macromolecules. No methods are available either for determining 

 the sequence of nucleotides in a polymer containing more than a few 

 elements. 



However, although the fine chemical structure of a nucleic acid is still 

 beyond our reach, genetic analysis can locate with extreme accuracy muta- 

 tion points within a genetic locus. It should be possible then to isolate 

 several mutants of the locus corresponding to a given enzyme and to locate 

 the mutation points within the locus by genetic analysis. The abnormal 

 proteins corresponding to each mutant could be isolated and their struc- 

 tures compared. If the hypothesis is correct, the locations of the changes in 

 the amino acid sequence should be correlated with the positions of the 

 mutations within the gene. 



Such an experiment will involve a considerable amount of skilled work. 

 It looks feasible with a suitable material : a small protein molecule easy to 

 isolate, produced by a micro-organism in which mapping can be performed 

 down to very narrow regions of the genome. 



A few laboratories are at present endeavouring to do such experiments, 

 the results of which will be watched with great curiosity (Levinthal, 1959; 

 Garen, 1960). 



