volume 10 Number 11982 Nucleic Acids Research Automatic construction of restriction ate maps

A computer program is described which constructs maps of restriction endonuclease cleavage sites in DNA molecules, given only the fragment lengths. The program utilizes fragment length data from single and double restriction enzyme digests to generate maps for linear or circular molecules. The search for a map can be limited to the unknown (insert) region of a recombinant phage or plasmid. Typical restriction maps with four or five enzymes which cut at three to five unknown sites can be calculated in a few minutes. INTRODOCTION Restriction enzymes are among the most powerful tools of molecular genetics. Together with recombinant DNA techniques, they have given biologists the ability to explore genes with an ease undreamed of ten years ago. Usually soon after a recombinant clone containing a DHA fragment of interest is identified, experiments are done to map its restriction sites. A number of techniques have been developed for ordering restriction fragments (1, 2, 3, 4). Preliminary maps can often be constructed from single and double restriction enzyme digestions by ordering and aligning the single enzyme digestion fragments to agree with the double enzyme digestions. However, in many cases mapping requires more complex and time-consuming experiments. In this paper we present computer programs that rapidly find restriction maps of circular and linear molecules. The programs search for a map in much the same way we do by hand- permuting the single enzyme fragments and aligning them until their overlap agrees with the double enzyme digestion data. Unlike most of us, however, the program finds all of the possible arrangements of fragments which agree with the data, and a molecule can often be mapped in a matter of minutes