Genome-Wide Strategies for Studying Gene Function by Using Model Systems

This chapter outlines how complete genome sequences promote the development of broad genome-wide or functional-genomics approaches for investigating individual genes to entire gene sets. Classical approaches had focused on a small portion of the Saccharomyces cerevisiae, Bacillus subtilis, and Escherichia coli genes. The power of genetically tractable model systems is that they facilitate the analysis of gene function at the level of the intact organism. In various adaptations of this method, PCR-generated replacement DNAs are used for constructing strains harboring simple point mutations or large deletions, making reporter gene constructs for any gene, inserting epitope or fluorescent tags in any protein, and studying the regulatory information controlling gene expression. Regulatable promoter replacement cassettes in combination with the availability of complete genome sequences will be important resources for studying gene function in yeasts and other eukaryotic systems. New methods for assessing gene expression, protein-protein interactions, and protein-nucleic acid interactions mean that it is now possible to use genome-wide approaches to study gene function. These global approaches should significantly accelerate progress toward a detailed understanding of the model organisms B. subtilis, E. coli, and S. cerevisiae. Genome-wide methods will generate exponentially increasing amounts of biological data. Effective systems of data storage, management, and analysis must keep pace with data generation so that the data and the tools necessary to apply these resources to individual research programs are accessible to all researchers.