Evolution of the MAT locus and its Ho endonuclease in yeast species

Abstract

The genetics of the mating-type (MAT) locus have been studied extensively in Saccharomyces cerevisiae, but relatively little is known about how this complex system evolved. We compared the organization of MAT and mating-type-like (MTL) loci in nine species spanning the hemiascomycete phylogenetic tree. We inferred that the system evolved in a two-step process in which silent HMR͞HML cassettes appeared, followed by acquisition of the Ho endonuclease from a mobile genetic element. Ho-mediated switching between an active MAT locus and silent cassettes exists only in the Saccharomyces sensu stricto group and their closest relatives: Candida glabrata, Kluyveromyces delphensis, and Saccharomyces castellii. We identified C. glabrata MTL1 as the ortholog of the MAT locus of K. delphensis and show that switching between C. glabrata MTL1a and MTL1␣ genotypes occurs in vivo. The more distantly related species Kluyveromyces lactis has silent cassettes but switches mating type without the aid of Ho endonuclease. Very distantly related species such as Candida albicans and Yarrowia lipolytica do not have silent cassettes. In Pichia angusta, a homothallic species, we found MAT␣2, MAT␣1, and MATa1 genes adjacent to each other on the same chromosome. Although some continuity in the chromosomal location of the MAT locus can be traced throughout hemiascomycete evolution and even to Neurospora, the gene content of the locus has changed with the loss of an HMG domain gene (MATa2) from the MATa idiomorph shortly after HO was recruited.M ating in Saccharomyces cerevisiae is a choreographed fusion of two haploid cells with opposite mating types to form a diploid zygote. The mating type of a haploid cell is determined by its genotype at the mating-type (MAT) locus on chromosome III. The two variants of the MAT locus, MAT␣ and MATa, are referred to as idiomorphs rather than alleles because they differ in sequence, size, and gene content (1). Characterization of homothallic and heterothallic strains of S. cerevisiae by Winge and Lindegren (2) led to the discovery of genetic loci controlling homothallism and ultimately to the cassette model of mating-type switching proposed by Herskowitz and colleagues (3). The cassette model, which has been thoroughly verified by experimentation (4, 5), states that a haploid cell can switch genotype at the MAT locus (from MATa to MAT␣ or vice versa) by a gene-conversion process that involves replacing the genetic information at MAT with information copied from one of two silent cassette loci, HML␣ or HMRa. The gene conversion is initiated at a double-stranded DNA break made by the Ho endonuclease, encoded by the HO gene on chromosome IV, which cuts at a site that marks the boundary between the Y sequences unique to the MATa or MAT␣ idiomorphs and the shared Z sequence flanking them. HO is expressed only in cells that have budded once, which means that only mother cells switch mating type and neighboring cells in a colony can mate (4). Hence, most natural isolates of S. cerevisiae are diploid and phenotypic...

Mating-type switching by chromosomal inversion in methylotrophic yeasts suggests an origin for the three-locusSaccharomyces cerevisiaesystem

“…1). Genome sequences show that almost all species in this family have three MAT-like loci and are likely to switch mating types by a mechanism similar to that of S. cerevisiae (8,29,34,35), although some species use an alternative mechanism instead of HO endonuclease to cut the MAT locus (15). Family Saccharomycetaceae is one clade within the subphylum Saccharomycotina, which also includes a large clade of Candida and related species (called the "CTG clade" because of its unusual genetic code).…”

Chromosome Loss Followed by Duplication Is the Major Mechanism of Spontaneous Mating-Type Locus Homozygosis in Candida albicans

“…Haploid S. cerevisiae can change its mating type by site-specific recombination at the MAT in culture (Lockhart et al 2002;Pujol et al 2003). MTL zygosity has been shown to regulate not only matlocus with a copy of the alternative silent locus (Butler et al 2004). This represents a conserved system, since ing competency, but also white-opaque switching.…”

Elaboration, Diversification and Regulation of the Sir1 Family of Silencing Proteins in Saccharomyces

“…Evolution of the SIR1 family: Prior to the detection of the KOS3 ortholog in Z. rouxii, it appeared as if the Sir1 family arose after the whole-genome duplication (Butler et al 2004). However, we are now able to position the appearance of Sir1 some time after the evolution of the mating cassettes, but before the genome duplication.…”

“…The Sir1's from the different species were between 77 and 58% identical to S. cerevisiae Sir1 across the entire protein sequence (Table 2). SIR1 was not found in C. glabrata ( Figure 1B), which contains silenced mating-type cassettes and shared a common ancestor with S. cerevisiae after the whole-genome duplication (Butler et al 2004;Conant and Wolfe 2006). The Sir1 found in S. castellii was the most divergent ortholog (Bose et al 2004).…”

“…rouxii KOS3 was apparently the only member of the Sir1/Kos family in a species that did not undergo the whole genome duplication. The Z. rouxii genome has not yet been completely sequenced, but shotgun coverage to approximately 13 depth on two different strains (Butler et al 2004;Gordon and Wolfe 2008) did not reveal any additional members of the family in this species. This observation raised the possibility that Z. rouxii Kos3 was an outgroup to all the other sequences in our analysis and therefore that Kos3 represented the ancestral gene.…”