The origins of replication of the yeast mitochondrial genome and the phenomenon of suppressivity.

Abstract

The ‘petite colonie’ mutation of Saccharomyces cerevisiae1,2 is characterized by an irreversible loss of respiration and by an extraordinarily high spontaneous mutation rate3,4. Crosses of wild-type cells with petite mutants exhibit a non-mendelian segregation of the mutation, yielding either wild-type progeny only1,2, or both wild-type and petite mutants in proportions essentially dependent on the particular petite used3. In the first case, the petites entering the cross are called neutral, in the second one suppressive3. While the molecular basis of the spontaneous petite mutation is now understood4–12, suppressivity has remained an elusive phenomenon for the past 25 yr. We report here that the mitochondrial genome of most spontaneous petites (which is exclusively made up by the tandem repetition of a DNA segment excised from the genome of parental wild-type cells5–8) carries at least one of the ori sequences of the parental wild-type genome. These are long homologous DNA stretches showing striking similarities with the origins of replication of mitochondrial DNAs from mammalian cells. The properties (intact or altered primary structure, high or low number) of the ori sequences of petite genomes seem to determine suppressivity—the level of transmission of petite genomes to the progeny of crosses with wild-type cells. These results indicate that ori sequences are indeed origins of DNA replication and that suppressivity depends on the relative replication efficiencies of petite and wild-type genomes.