Array of hope

The genome project has revitalized exploration in biological research. Not long ago, it was possible for biologists to imagine that the genes that had been discovered via mutations, selections and cloning schemes represented a good approximation of the total universe of genes, and that the proteins already discovered on the basis of their abundance, location, or activity well represented the total universe of proteins. One of the great contributions of the genome project has been to show us what a small part of this world was really known to us, and how much of this world remains to be explored. In April 1996, the complete sequence of the yeast genome confronted us with the fact that yeast contain approximately 6,200 'real' genes, as judged from open reading frames, for only one quarter of which could we hazard a guess regarding function 1 The tens of thousands of partial human cDNA sequences representing previously unseen genes have had a similar humbling effect 2. Although we may have suspected its existence, the actual discovery of this genetic terra incog-nita has jolted biology much as the discovery of America jolted Europe 500 years agoshowing us how much of the world is beyond the frontier—mysterious, tantalizing and unexplored. Exploring the genome and the natural world with DNA microarrays Exploration means looking around, observing, describing and mapping undiscovered territory, not testing theories or models. The goal is to discover things we neither knew or expected, and to see relationships and connections among the elements, whether previously suspected or not. It follows that this process is not driven by hypothesis and should be as model-independent as possible (see page 54 of this issue (ref. 3)). We should use the unprecedented experimental opportunities that the genome sequences provide to take a fresh, comprehensive and open-minded look at every question in biology. If we succeed, we can expect that many of the new models that emerge will defy conventional wisdom. Exploring and surveying are best done systematically. The genome, representing the complete blueprint of the organism, is the natural bounded system in which to conduct this exploration. The completion of the genomic sequences of 'model organisms' (currently the eukaryotes Saccharomyces cerevisiae and Caenorhabditis elegans, as well as dozens of bacterial species) provides us with such complete blueprints These genome sequences have not only made a new era of exploration imperative, but, providentially, they have also made it possible. …

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