Over 50 years ago, in a lab in France, Ephrussi, et al. discovered a non-Mendelian inherited factor that is essential to respiration in the yeast, Saccharomyces cerevisiae.  S. cerevisiae without this factor, known as the ρ-factor, is described by the development of small colonies when compared to the wild-type yeast.  These smaller colonies were dubbed petite colonies.  These petite mutants were observed to be spontaneously produced naturally at a rate of 0.1%-1.0% every generation. They also found that treatment of wild-type S. cerevisiae with DNA-intercalating agents would more rapidly produce this mutation.
Schatz identified a region of the yeast's nuclear DNA that was associated with the mitochondria in 1964. Later, it was discovered that mutants without the ρ-factor had no mitochondrial DNA (called ρ isolates), or that they possessed a difference in density or amount of the mitochondrial DNA (called ρ isolates). The use of electron microscopy to view the DNA in the mitochondrial matrix helped to verify the actuality of the mitochondrial genome.
S. cerevisiae has since become a useful model for aging. It has been shown that as yeast ages, it loses functional mitochondrial DNA, which leads to replicative senescence, or the inability to further replicate.  It has been suggested that there is a link between mitochondrial DNA loss and replicative life span (RLS), or the number of times a cell can reproduce before it dies, as it has been found that an increase in RLS is established with the same changes in the genome that enhance the propagation of cells that do not contain mitochondrial DNA.  Genetic screens for replicative life span associated genes and pathways could be made easier and quicker by selecting genetic suppressors of the petite negative mutants.