8.3 Mating type switching in budding yeast
Saccharomyces cerevisiae is heterothallic but a clone of haploid cells of the same mating type frequently sporulates, and there will be equal numbers of a and α cells amongst the progeny. This results from mating type switching controlled by the gene HO (HOmothallic) that exists in two allelic forms (dominant HO and recessive ho), and encodes an endonuclease. On either side of the MAT locus, and on the same chromosome, there are silent storage loci for each mating type, called HML and HMR. The HO/ho endonuclease creates a double-strand break at the MAT locus that initiates switching of information, by an homologous recombination event between the two parts of the same chromosome, at the MAT locus with that at either HML or HMR (Fig. 4).
|Fig. 4. Top: pattern of mating type switching in Saccharomyces cerevisiae showing the consequences of a mating type switch in one mother cell. Bottom: the three loci involved in mating type switching, HML, MAT and HMR, are located on the same chromosome (not drawn to scale). HML is about 180 kb from MAT, and HMR about 120 kb from MAT; the centromere is located between RE and the MAT locus. A double strand break at the MAT locus, caused by the HO endonuclease, initiates a recombination event that replaces the Y region of the MAT locus with Y sequences from one of the storage loci. HML and HMR contain complete copies of the mating type genes but are not expressed because they have a repressed chromatin structure imposed by the E and I silencer sequences. HML shares more of the MAT sequences (W, X, Z1 and Z2) than does HMR. RE is a recombination enhancer that controls preferential recombination between MATa and HML, or between MATa and HMR. Modified from Chapter 2 in Moore & Novak Frazer, 2002.|
Since yeasts can live in very small habitats, like flower nectaries and surfaces of individual fruits, yeast populations can be very isolated from one another in nature, so the rare mating type switching will give isolated populations the opportunity to undergo sexual reproduction; this is presumably its selective advantage. Mating type switching occurs about once in 105 divisions in cultures carrying allele ho, whereas in strains carrying HO the switch occurs at every cell division. However, there is an asymmetry in the cell division in that a new daughter bud is not able to switch mating types until it has itself budded. In S. cerevisiae, this is achieved by actively transporting the mRNA of a gene called Ash1 into the budding daughter cell. This mRNA encodes an inhibitor of the HO-endonuclease. Consequently, immediately after each division switching by the daughter is inhibited and only the mother cell is switchable. This means that even if there is only one cell to start with, a single division cycle will produce two cells of opposite mating type.
If you think that’s a well-adapted arrangement, the switch to opposite mating type is assured because a 250 bp recombination enhancer controls recombination in the arm of chromosome III on which all these genes are located. This control region ensures that in MATa cells the resident MATa locus recombines with HML, which contains a silent MATa locus, whereas in MATa cells the resident locus recombines with HMR, which contains a silent MATa locus. Now, that’s well-adapted.
Mating type switching also occurs in the distantly related fission yeast Schizosaccharomyces pombe but this organism uses the asymmetry of DNA replication to establish an asymmetrical mating-type switching pattern (Dalgaard & Klar, 2001). When S. pombe divides, the two daughter cells exhibit different developmental programmes: one is mating type switchable, the other is unswitchable. Genetic experiments show that in switchable cells the expressed (mat1) mating type locus has an imprint that marks it as a candidate for the intrachromosomal recombination event that makes the mating type switch. The imprint is a modification in one strand of the DNA, possibly a ‘nick’ (a broken phosphodiester bond) or an RNA primer left from the DNA synthesis during the previous mitotic division. During DNA replication the strand-specific imprint is made at the mat1 locus only during lagging-strand synthesis, so only one of the sister chromatids will carry the imprint. The cell that inherits the imprinted chromosome becomes a switchable cell, while its sister remains unswitchable. When the imprinted chromosome is replicated, the DNA replication complex runs into the imprinted modification in the DNA, the replication fork stalls, and the result is a transient double strand break that initiates the recombination required for mating-type switching.
Mating types in filamentous fungi tend to be far more stable although unidirectional switching of mating type has been reported in some filamentous ascomycetes, though with no molecular details yet. Oddly enough, switching does not occur in any of the best-studied organisms like Neurospora, Aspergillus, or Podospora, but has been claimed in Chromocrea spinulosa, Sclerotinia trifoliorum, Glomerella cingulata and Ophiostoma ulmi.
Updated December 17, 2016