The analysis of gene functions depends on two complementary approaches: genetics and biochemistry. Genetics starts with the study of mutants: we either find or make an organism in which a gene is altered, and then examine the effects on the organism’s structure and performance (Figure 1–23). Biochemistry more directly examines the functions of molecules: here we extract molecules from an organism and then study their chemical activities. By combining genetics and biochemistry, it is possible to find those molecules whose production depends on a given gene. At the same time, careful studies of the performance of the mutant organism show us what role those molecules have in the operation of the organism as a whole. Thus, genetics and biochemistry used in combination with cell biology provide the best way to relate genes and molecules to the structure and function of an organism.
In recent years, DNA sequence information and the powerful tools of molecular biology have accelerated progress. From sequence comparisons, we can often identify particular subregions within a gene that have been preserved nearly unchanged over the course of evolution. These conserved subregions are likely to be the most important parts of the gene in terms of function. We can test their individual contributions to the activity of the gene product by creating in the laboratory mutations of specific sites within the gene, or by constructing artificial hybrid genes that combine part of one gene with part of another. Organisms can be engineered to make either the RNA or the protein specified by the gene in large quantities to facilitate biochemical analysis. Specialists in molecular structure can determine the three-dimensional conformation of the gene product, revealing the exact position of every atom in it. Biochemists can determine how each of the
Figure 1–23 A mutant phenotype reflecting the function of a gene. A normal yeast (of the species Schizosaccharomyces pombe) is compared with a mutant in which a change in a single gene has converted the cell from a cigar shape (left) to a T shape (right). The mutant gene therefore has a function in the control of cell shape. But how, in molecular terms, does the gene product perform that function? That is a harder question, and it needs biochemical analysis to answer it. (courtesy of kenneth sawin and Paul nurse.) parts of the genetically specified molecule contributes to its chemical behavior. Cell biologists can analyze the behavior of cells that are engineered to express a mutant version of the gene.
There is, however, no one simple recipe for discovering a gene’s function, and no simple standard universal format for describing it. We may discover, for example, that the product of a given gene catalyzes a certain chemical reaction, and yet have no idea how or why that reaction is important to the organism. The functional characterization of each new family of gene products, unlike the description of the gene sequences, presents a fresh challenge to the biologist’s ingenuity. Moreover, we will never fully understand the function of a gene until we learn its role in the life of the organism as a whole. To make ultimate sense of gene functions, therefore, we have to study whole organisms, not just molecules or cells.
molecular Biology Began with a spotlight on E. coli
Because living organisms are so complex, the more we learn about any particular species, the more attractive it becomes as an object for further study. Each discovery raises new questions and provides new tools with which to tackle general questions in the context of the chosen organism. For this reason, large communities of biologists have become dedicated to studying different aspects of the same model organism.