Genetics of evolved resistance to a natural yeast parasite

Selfish genetic elements exploit host cell machinery for their own reproduction, thereby reducing host fitness. How do host cells evolve to defend themselves against these genetic parasites? We hypothesize that the 2-micron plasmid, naturally found in many budding yeasts, is one example of a selfish element. The plasmid must hijack host cellular machinery to replicate and segregate its genome, and confers a fitness cost to the host in the process.    We have identified several natural Saccharomyces cerevisiae isolates that naturally do not harbor the 2-micron.  When we reintroduce the plasmid, these strains rapidly and reproducibly lose the 2-micron once again, suggesting this plasmid loss is a heritable trait. Furthermore, this plasmid loss phenotype is a genetically dominant trait.  Taken together, we hypothesize these strains may have evolved a restriction factor targeting the 2-micron plasmid.  Using a quantitative trait locus mapping strategy we have identified a region of the genome associated with this plasmid restriction.  We are currently experimentally validating this region and testing candidate genes for plasmid restriction. Our future directions will be exploring the molecular mechanisms underlying this trait.   This genetically tractable, yet naturally occurring, host-parasite model provides insight into how host cells can evolve to fight genetic parasites.