PEROXISOME BIOGENESIS IN THE YEAST HANSENULA-POLYMORPHA IS CONTROLLEDBY A COMPLEX SET OF INTERACTING GENE-PRODUCTS

We have studied the genetic interactions between mutant alleles in 12 genes, designated PER1-PER12, which are essential for peroxisome bioge nesis in the yeast Hansenula polymorpha. Recessive mutations in any of these genes determined three different morphological phenotypes: (i) complete absence of peroxisomes (Per-); (ii) presence of small peroxis omes in conjunction with a major fraction of peroxisomal matrix protei ns in the cytosol (Pim-); and (iii) presence of peroxisomes with aberr ant crystalline matrix substructure (Pss-). Extensive complementation analysis showed many cases of noncomplementation-that is, diploids tha t contained both wild-type and mutant alleles of two different PER gen es were unable to grow on methanol and showed peroxisomal defects. The observed cases of unlinked noncomplementation appeared to be gene and allele specific and were predominantly observed at lower temperatures (cold sensitive). The genetic results obtained were used to formulate a model of PER gene product interactions. In this model, five PER gen e products are key or core components of the complex. Other PER gene p roducts appear to play a more peripheral role.