Molecular Revolution

From the one gene-one enzyme hypothesis arose the concept of colinearity of gene and protein, i.e., the linear array of DNA nucleotide base sequence specifies the linear array of amino acids in the protein. Since the amino acid sequence of a protein was not yet known, Beadle and Tatum did not know the way in which genes determined enzymes. However, the biochemical genetic work initiated by Neurospora inspired workers using E. coli and yeast and was a starting point of a molecular revolution in biology. It was established that allelic forms of a gene specify structurally different forms of the same enzyme. Further, it was observed that certain pairs of mutants, deficient in the same enzyme, cooperated in diploid or in a heterokaryon to produce significant amounts of enzyme activity, i.e., the polypeptide chains from different mutants corrected each other's defects (allelic complementation). It was shown that many enzyme proteins contain more than one polypeptide chain, each specified by a different gene. The formation of active enzyme molecules was explained as molecular hybrids in which polypeptide chains from different mutants corrected each other's defects through effects on polypeptide conformation. These observations led to the modification of the one gene-one enzyme hypothesis to the one gene-one polypeptide hypothesis. The basic relationships between genes, proteins and phenotypes thus understood, attention turned to how the activities of enzymes are controlled. This led to the formulation of the operon model of control of gene activity from work done with E. coli. After the genetic basis of the enzyme structure was established, the work with E. coli led to investigations of the regulation of gene activity, stimulated by the lactose operon model of Jacob and Monod. The growth tests with the auxotrophic mutants of Neurospora started a molecular revolution in biology. "It became the preferred way to dissect complex biological systems such as embryonic development, cell division, the nature of sensory systems, and aging. Today, mutational analysis is the preferred way into a complex biological problem, especially as it provides access to the genes and protein players" (Horowitz et al., 2004).

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