Replicator regions of the yeast mitochondrial DNA responsible for suppressiveness

Hypersuppressiveness is a heritable property of some rho- mutants (called HS) that, in crosses to rho+, give rise to about 100% rho- cells. The mtDNAs of all HS rho- mutants reveal a common organization: they all share a homologous region of about 300 base pairs (called rep) and the fragments retained are always short (ca. 1% of the wild-type genome) and tandemly repeated. Using one HS rho- mutant as an example, we show that, after crosses with rho+ strains, the mitochondrial genome of the progeny is indistinguishable from that of the HS parent. This suggests that HS mtDNA molecules have a decisive selective advantage for replication during the transient heteroplasmic stage that follows zygote formation, the rep regions playing a role in the control of replication initiation of the mtDNA molecules. The complete nucleotide sequence of one HS rho- mutant and its localization in the oli1-rib3 segment of the rho+ mitochondrial genome are presented. Comparison of the nucleotide sequences of the rep regions of two different HS rho- mutants reveals that several rep sequences must exist in the wild-type genome, probably as a result of duplications of an originally unique ancestor.