We study the mechanisms by which extra-genomic nucleic acid elements evolve to become stably propagating entities in the host population. We use a common high copy number plasmid in yeast, the 2 micron circle, as a model system. The plasmid has acquired the capacity to couple its partitioning during cell division to that of its host chromosomes. It also keeps in reserve an amplification system to counteract any downward trend in copy number due to an accidental missegregation event. By combining the partitioning and amplification systems judiciously, the plasmid is able to persist in yeast populations, even though it does not confer any selective advantage to the host.
In one set of investigations, we attempt to understand the molecular trickery by which the plasmid is able to feed into the chromosome segregation pathway. In another, we explore the molecular details of the copy number amplification pathway. The basic event here is a site-specific DNA recombination event coupled to the replication of the plasmid. We also try to apply the recombination system to bring about directed DNA rearrangements in large genomes-the basic principle of gene targeting and gene therapy.