The original technique of chromosome jumping was developed in the laboratories of Collins and Weissman at Yale University in New Haven, U.S. and the laboratories of Poustka and Lehrach at the European Molecular Biology Laboratory in Heidelberg, Germany.
Collins and Weissman's method described above encountered some early limitations. The main concern was with avoiding non-circularized fragments. Two solutions were suggested: either screening junction fragments with a given probe or adding a second size-selection step after the ligation to separate single circular clones (monomers) from clones ligated to each other (multimers). The authors also suggested that other markers such as the λ cos site or antibiotic resistance genes should be considered (instead of the amber suppressor tRNA gene) to facilitate selection of junction clones.
Poustka and Lehrach suggested that full digestion with rare-cutting restrictions enzymes (such as NotI) should be used for the first step of the library construction instead of partial digestion with a frequently cutting restriction enzyme. This would significantly reduce the number of clones from millions to thousands. However, this could create problems with circularizing the DNA fragments since these fragments would be very long, and would also lose the flexibility in choice of end points that one gets in partial digests. One suggestion for overcoming these problems would be to combine the two methods, i.e. to construct a jumping library from DNA fragments digested partially with a commonly cutting restriction enzyme and completely with a rare cutting restriction enzyme and circularizing them into plasmids cleaved with both enzymes. Several of these "combination" libraries were completed in 1986.
In 1991, Zabarovsky et al. proposed a new approach for construction of jumping libraries. This approach included the use of two separate λ vectors for library construction, and a partial filling-in reaction that removes the need for a selectable marker. This filling-in reaction worked by destroying the specific cohesive ends (resulting from restriction digests) of the DNA fragments that were nonligated and noncircularized, thus preventing them from cloning into the vectors, in a more energy-efficient and accurate manner. Furthermore, this improved technique required less DNA to start with, and also produced a library that could be transferred into a plasmid form, making it easier to store and replicate. Using this new approach, they successfully constructed a human NotI jumping library from a lymphoblastoid cell line and a human chromosome 3-specific NotI jumping library from a human chromosome 3 and mouse hybrid cell line.