A Gene Concept Based on Genetic and Chemical Studies in Neurospora

Two methods of analysis of the fine structure of genes are discussed. These methods yield data that support the concept of linear organization within a gene. This organization is apparent in both genetic and complementation maps. Experiments designed to give information concerning the mechanism of complementation are described. These data indicate that it is possible to simulate complementation in vivo. In this case complementation in vivo in Neurospora crassa is characterized by the ability of two ad-4 mutants growing together as a heterocaryon to produce functional adenylosuccinase, which neither mutant can make when grown alone. The simulated complementation occurs in vitro by mixing partially purified and presumably differentially defective forms of mutant adenylosuccinase. Maximum efficiency of complementation in vitro is obtained when attempting to modify or interchange-SH and-S-S-bonds of the protein. Theoretically, such a treatment could result in the formation of aggregates, hybrid molecules, or complexes of various forms. It is postulated that if this means of restoring enzyme activity is the mechanism of complementation in vivo, then the complementation maps is a reflection of the structure and properties of the enzyme rather than the gene. The similarities between genetic and complementation maps can be accounted for by a template model for the gene-protein relationship. This theory also explains occasional discrepancies between genetic and complementation maps, since such maps presumably correspond respectively to the structure of different macromolecules, DNA in the former case, protein in the latter.