MaRX: an approach to genetics in mammalian cells

A genetic approach is the most direct way to elucidate biological processes that are poorly understood. One of the first such efforts—the landmark study of Beadle and Tatum (1) on the genetics of metabolic pathways—established the influential “one gene, one enzyme” hypothesis. In subsequent decades, the yeasts Saccharomyces cerevisiae and S. pombe became the premier genetic models. The oft-touted “power of yeast genetics” was not fully realized, however, until classical techniques were combined with an ability to manipulate the organisms with recombinant DNA methods (2–4). Thus were conceived the tools that today make yeasts the best-characterized eukaryotes. These tools, however, have limitations: accumulating human sequence data reveals many genes that are not represented in yeast. How can the leap be made from yeast to human