CYP3–15: An up-promoter mutation at the ISO-2 cytochrome c structural gene locus and its interaction with other independent regulatory mutations of cytochrome c synthesis in Saccharomyces cerevisiae

Summary

The occurrence of “up promoter” mutations appears to be a general feature of eukaryotic gene regulation. Such mutations have been described in organisms as different as Yeast, Aspergillus, and Drosophila (Douglas and Hawthorne, 1966; Arst and Scazzochio, 1975; Hynes, 1975; Ciriacy, 1976; Chovnick et al., 1976), yet little is known about the underlying regulatory mechanisms.

Some years ago, Clavilier et al. (Clavilier et al., 1969) discovered in S. cerevisiae regulatory mutations enhancing the synthesis of iso-2 cytochrome c. One of these mutations was found to entail a secondary phenotype prohibiting growth on a glucose medium containing high levels of chloramphenicol (Péré-Aubert, 1970).

In this paper evidence is presented that:

• 1. This regulatory mutation, CYP3-15, is linked to the structural gene of iso-2 cytochrome c, is cis dominant, and therefore qualifies as an “up promoter” mutation of the iso-2 cytochrome c producing unit.

• 2. The secondary phenotype entailed by CYP3-15 never occurs in the absence of the main phenotype of iso-2 cytochrome c stimulation, and is a consequence of the extension into a nearby function of the genetic alteration corresponding to CYP3-15. This secondary phenotype is manifest whatever the genotype at the CYC1 locus, including in the presence of the wild type allele.

• 3. Despite being cis dominant, CYP3-15 is still receptive to the effect of three other independent regulatory mutations. One of these, which reduces both the iso-1 and iso-2 cytochrome c level, is a null allele of the CYP1 locus. This later locus was also originally identified by mutations which enhance, to various degrees, the amount of iso-2 cytochrome c produced by the cell (Clavilier et al., 1976).