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ABSTRACT
It has been 33 years since I first presented results of genetic experiments that established the gene transposition model as the mechanism of mating-type switching in the budding yeast Saccharomyces cerevisiae at the Cold Spring Harbor Laboratory (CSHL) Yeast Genetics meeting in August 1977. Over two decades ago the Genetics Perspectives editors solicited a perspective on my participation in the studies that deciphered the mechanism of mating-type switching and revealed the phenomenon of gene silencing in yeast. Although flattered at the time, I thought that preparation of such an article called for a more seasoned researcher who had benefitted from seeing his contributions stand the test of time. Now realizing that our discovery of the transposition of a mutation from the HMα locus into the MAT (mating type) locus has provided the genetic evidence that established the gene transposition model, and having witnessed our conclusions confirmed by subsequent molecular studies, I decided that perhaps this is a good time to recount the chronology of events as they unfolded for me decades ago.
THE sexual cell types of yeast are designated a and a, which are correspondingly conferred by the MATa and MATa alleles of the mating type locus (MAT). Cells of opposite type can mate to establish a cell of the MATa/MATa diploid state (Figure 1). Because both MAT alleles are co-dominant, such diploid cells are sterile but can undergo meiosis and sporulation to form asci, each of which contains two MATa and two MATa haploid spores. In so-called heterothallic strains (those containing the nonfunctional ho gene), the MAT alleles switch rarely (<1 × 10-6), but the unusual homothallic (those containing the functional HO gene) cells switch mating type remarkably efficiently, within a few cell divisions after the spore germinates. The cells in the incipient colony of the opposite type mate to reestablish MATa/ MATa diploid cells in which the HO gene and the switching process are shut off (Winge and Roberts 1949). This was an odd and fascinating phenomenon that workers in the field initially cracked open by conventional genetics. This Perspectives is about my postdoctoral training research, during which different aspects of the mystery were cleared up by a series of informative experiments. This is a personal account of the excitement...