The goal of this project is to develop a unified physical and genetic map for yeast. Through the work of many investigators, the linkage map for Saccharomyces is well developed, with the latest edition including 568 markers mapped to 16 chromosomes. Over 120 of these genes have been cloned. Despite this wealth of data about both the genetic and physical structure of the yeast genome, little long-range physical mapping has been done. With a relatively small genome (15,000 kb), little repetitive DNA, and well developed molecular genetics, yeast offers a good system in which to develop DNA-mapping methods with more power than those presently available. In this project, considerable progress has already been made towards a global physical map of the yeast genome. A set of 4644 lambda clones, containing random 13.5-kb inserts of yeast DNA, has been analyzed by restriction-enzyme digestion, and the fragment-size lists for these clones have been entered into a computerized data base. These data provide a sampling of genomic DNA with a redundancy of approximately 4.2. Computer-based algorithms have been developed that allow the construction of local maps around arbitrarily selected seed clones. These techniques are presently being extended from test cases to the entire random-clone data base. Experience with test cases suggests that, on the first pass through the data base, local maps may be expected to include an average of 10 clones, to span 30 kb, and to have a resolution of 3 kb. On subsequent passes, it should be possible to build up larger maps, but the process will utimately be limited by the incompleteness of the random-clone collection. In parallel with the analysis of random clones, the chromosonal DNA molecules of yeast have been separated electrophoretically and identified. For several of the chromosomes, the fragments produced by SfiI digestion, which average 200 kb in size, have also been separated, and these fragments are being identified with the use of DNA-DNA hybridization probes prepared from cloned, genetically mapped genes. Future work will emphasize completion of the analysis of the random-clone data, and the development of long-range continuity in the physical map. Continuity will be sought primarily by associating the high-resolution local maps from the random-clone data with specific, electrophoretically separated chromosome sub-fragments, as well as with specific regions of the genetic map.
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