Yeast Mating Type

Saccharomyces cerevisiae, baker’s yeast, can exist in either a haploid (1n) or a diploid (2n) state. Haploids express one of two mating types, a or a (alpha). Haploids of either mating type are capable of mating with haploids of the opposite mating type in response to the action of mating pheromones. Mating results in fusion of haploid cells, forming an a/a diploid, which is no longer capable of mating. Genetic analysis in the early days of yeast research showed that mating type was controlled by alleles of a single genetic locus, referred to as MAT (mating type). Haploid strains possess either the MATa or MATa allele; a/a diploids are heterozygous at this locus, carrying both alleles. Both haploids and diploids can undergo vegetative growth (mitotic cell cycles); a/a diploids are also capable of undergoing meiosis to produce four haploid nuclei, which are then packaged into ascospores. The four products of a singlemeiosis are held together in a sac called an ascus. The alleles of the mating type locus segregate during meiosis, producing twomating type a spores and twomating type a spores in each ascus. Spores return to a vegetative growth pattern under appropriate nutritional conditions. The genetic analysis of yeast mating type began with the isolation of sterile (ste) mutants unable to mate (MacKay andManney, 1974a). They screened among amutagenized population of a cells that carried a recessive drug resistance marker to find isolates that grew on selective medium containing the drug even whenmixed with a large excess of a mating type cells bearing the dominant sensitivity allele. Someof these sterilemutants haddefects at themating type locus itself, while others mapped to different locations in the genome. These workers carried out additional studies to obtain sterilemutations in an abackground. Subsequent analysis indicated that the sterile mutants not mapping to themating type locus fell into one of three categories: those that caused sterility only in an a background, those that caused sterility only in an a background, and the majority class that were not specific and resulted in sterility in the presence of either allele at the mating type locus (MacKay and Manney, 1974b). Sterile mutants mapping to the mating type locus provided important information about its structure and function. Two complementation groups of sterile mutants atMATa were found, thus identifying two different genes at this locus. Interestingly, mutants of these two genes had different phenotypes: mata1 mutants showed reduced mating with both a and a and failed to produce a-factor or agglutinate with a cells; rare MATa/mata1 diploids could be constructed and these could sporulate. On the other hand, mata2 mutants were specifically defective in matingwith a cells and showed two a-like phenotypes: they responded to a-factor and, at low efficiency, mated as a cells. When MATa/mata2 diploids were constructed, they were found to be unable to sporulate. No mutations of MATawere found among the original sterile mutants; as it happens, these do not affect mating ability. They were foundlaterthroughtheireffectsondiploids(MATa1/MATa cells mate as a and do not sporulate). The properties of these mutations at the mating type locus led to theproposal of the ‘a1–a2model’ for control of cell type (reviewed in Herskowitz and Oshima, 1981). This hypothesis stated: (1) that theMATa1 gene product acts as a positive regulator of a-specific functions presumed to be encoded by a-specific genes; (2) that the MATa2 gene product is a negative regulator of a-specific functions presumed to be encoded by a-specific genes; and (3) that sporulation requires both a anda information, presumably the products of theMATa1 andMATa2 genes. Thismodel made several specific predictions, whichwere subsequently tested and confirmed. Molecular analysis of the mating type locus revealed the basis of the action of its gene products. The products of MATa1, MATa1 and MATa2 are transcriptional regulators that function in various combinations to regulate expression of genes that give a and a haploids and a/a diploids their unique properties, as shown in Figure 1. In a cells, Mata1p associates with the product of the MCM1 gene to form an activator of a-specific genes. Mata2p also associates with Mcm1p to repress a-specific genes. In a cells, neither Mata1p nor Mata2p is present, and thus aspecific genes are expressed (through the action of Article