Replication and preferential inheritance of hypersuppressive petite mitochondrial DNA

Wild-type yeast mitochondrial DNA (mtDNA) is inherited biparentally, wherea s mtDNA of hypersuppressive petite mutants is inherited uniparentally in cr osses to strains with wild-type mtDNA. Genomes of hypersuppressive petites contain a conserved ori sequence that includes a promoter, but it is unclea r whether the ori confers a segregation or replication advantage. Fluoresce nt in situ hybridization analysis of wild-type and petite mtDNAs in crosses reveals no preferential segregation of hypersuppressive petite mtDNA to fi rst zygotic buds. We identify single-stranded DNA circles and RNA-primed DN A replication intermediates in hypersuppressive petite mtDNA that are absen t from non-hypersuppressive petites. Mutating the promoter blocks hypersupp ressiveness in crosses to wild-type strains and eliminates the distinctive replication intermediates. We propose that promoter-dependent RNA-primed re plication accounts for the uniparental inheritance of hypersuppressive peti te mtDNA.