Inversion of the Chromosomal Region between Two Mating Type Loci Switches the Mating Type in <i>Hansenula polymorpha</i>

<div><p>Yeast mating type is determined by the genotype at the mating type locus (<i>MAT</i>). In homothallic (self-fertile) Saccharomycotina such as <i>Saccharomyces cerevisiae</i> and <i>Kluveromyces lactis</i>, high-efficiency switching between <b>a</b> and α mating types enables mating. Two silent mating type cassettes, in addition to an active <i>MAT</i> locus, are essential components of the mating type switching mechanism. In this study, we investigated the structure and functions of mating type genes in <i>H. polymorpha</i> (also designated as <i>Ogataea polymorpha</i>). The <i>H. polymorpha</i> genome was found to harbor two <i>MAT</i> loci, <i>MAT1</i> and <i>MAT2</i>, that are ∼18 kb apart on the same chromosome. <i>MAT1</i>-encoded α1 specifies α cell identity, whereas none of the mating type genes were required for <b>a</b> identity and mating. <i>MAT1</i>-encoded α2 and <i>MAT2</i>-encoded <b>a</b>1 were, however, essential for meiosis. When present in the location next to <i>SLA2</i> and <i>SUI1</i> genes, <i>MAT1</i> or <i>MAT2</i> was transcriptionally active, while the other was repressed. An inversion of the <i>MAT</i> intervening region was induced by nutrient limitation, resulting in the swapping of the chromosomal locations of two <i>MAT</i> loci, and hence switching of mating type identity. Inversion-deficient mutants exhibited severe defects only in mating with each other, suggesting that this inversion is the mechanism of mating type switching and homothallism. This chromosomal inversion-based mechanism represents a novel form of mating type switching that requires only two <i>MAT</i> loci.</p>