Themating of yeast, also known asyeast sexual reproduction, is a biological process that promotesgenetic diversity and adaptation inyeast species. Yeast species, such asSaccharomyces cerevisiae (baker's yeast), are single-celledeukaryotes that can exist as eitherhaploid cells, which contain a single set ofchromosomes, or diploid cells, which contain two sets of chromosomes. Haploid yeast cells come in twomating types,a and α, each producing specificpheromones to identify and interact with the opposite type, thus displaying simplesexual differentiation.[a] A yeast cell's mating type is determined by a specificgenetic locus known asMAT, which governs its mating behaviour. Haploid yeast can switch mating types through a form ofgenetic recombination, allowing them to change mating type as often as everycell cycle. When two haploid cells of opposite mating types encounter each other, they undergo a complexsignaling process that leads to cell fusion and the formation of a diploid cell. Diploid cells canreproduce asexually, but under nutrient-limiting conditions, they undergomeiosis to produce new haploid spores.
The differences betweena and α cells, driven by specificgene expression patterns regulated by theMAT locus, are crucial for the mating process. Additionally, the decision to mate involves a highly sensitive and complex signaling pathway that includes pheromone detection and response mechanisms. In nature, yeast mating often occurs between closely related cells, although mating type switching and pheromone signaling allow for occasionaloutcrossing to enhancegenetic variation. Certain yeast species have unique mating behaviors, demonstrating the diversity and adaptability of yeast reproductive strategies.
Yeast cells can stably exist in either a diploid or a haploid form. Both haploid and diploid yeast cells reproduce bymitosis, in which daughter cells bud from mother cells. Haploid cells are capable of mating with other haploid cells of the opposite mating type (ana cell can only mate with an α cell and vice versa) to produce a stable diploid cell. Diploid cells, usually upon facing stressful conditions like nutrient depletion, can undergomeiosis to produce four haploidspores: twoa spores and two α spores.[1][2]
Two haploid yeast of opposite mating types secrete pheromones, grow projections, and mate
a cells producea-factor, a matingpheromone which signals the presence of ana cell to neighbouring α cells.[3]a cells respond to α-factor, the α cell mating pheromone, by growing a projection (known as a shmoo, due to its distinctive shape resembling theAl Capp cartoon characterShmoo) towards the source of α-factor.[4] Similarly, α cells produce α-factor, and respond toa-factor by growing a projection towards the source of the pheromone.[5] The selective response of haploid cells to the mating pheromones of the opposite mating type allows mating betweena and α cells, but not between cells of the same mating type.[6]
Thesephenotypic differences betweena and α cells are due to a different set ofgenes being activelytranscribed and repressed in cells of the two mating types.a cells activate genes which producea-factor and produce acell surface receptor (Ste2) which binds to α-factor and triggerssignaling within the cell.[7][8]a cells also repress the genes associated with being an α cell. Conversely, α cells activate genes which produce α-factor and produce a cell surface receptor (Ste3) which binds and responds toa-factor, and α cells repress the genes associated with being ana cell.[9]
The different sets of transcriptional repression and activation, which characterizea and α cells, are caused by the presence of one of twoalleles for amating-type locus calledMAT:MATa orMATα located on chromosome III.[10] TheMAT locus is usually divided into five regions (W, X, Y, Z1, and Z2) based on the sequences shared among the two mating types.[11] The difference lie in the Y region (Ya and Yα), which contains most of the genes and promoters.[7]
TheMATa allele ofMAT encodes a gene calleda1, which directs thea-specific transcriptional program (such as expressingSTE2 and repressingSTE3) that defines ana haploid cell. TheMATα allele ofMAT encodes the α1 and α2 genes, which directs the α-specific transcriptional program (such as expressingSTE3, repressingSTE2, and producingprepro-α-factor) that defines an α haploid cell.[7]S. cerevisiae has ana2 gene with no apparent function that shares much of its sequence with α2; however, other yeast species likeCandida albicans do have a functional and distinctMATa2 gene.[6][10]
Regulation of mating in haploid and diploid yeast cells using theMAT locus
Haploid cells are one of two mating types (a or α) and respond to the mating pheromone produced by haploid cells of the opposite mating type.[4] Haploid cells cannot undergomeiosis.[12]Diploid cells do not produce or respond to either mating pheromone and do not mate, but they can undergomeiosis to produce four haploid cells.[13]
Like the differences between haploida and α cells, different patterns of gene repression and activation are responsible for thephenotypic differences between haploid and diploid cells.[14] In addition to the transcriptional patterns ofa and α cells, haploid cells of both mating types share a haploid transcriptional pattern which activates haploid-specific genes (such asHO) and represses diploid-specific genes (such asIME1).[15] Conversely, diploid cells activate diploid-specific genes and repress haploid-specific genes.[16]
The different gene expression patterns of haploid and diploid cells are attributable to theMAT locus. Haploid cells only contain one copy of each of the 16chromosomes and therefore only possess oneMAT allele (eitherMATa orMATα), which determines their mating type.[17] Diploid cells result from the mating of ana cell and an α cell, and they possess 32 chromosomes (in 16 pairs), including one chromosome bearing theMATa allele and another chromosome bearing theMATα allele.[18] The combination of the information encoded by theMATa allele (thea1 gene) and theMATα allele (the α1 and α2 genes) triggers the diploid transcriptional program.[19] Conversely, the presence of only oneMAT allele, eitherMATa orMATα, triggers the haploid transcriptional program.[20][7]
Throughgenetic engineering, aMATa allele can be added to aMATα haploid cell, causing it to behave like a diploid cell.[21] The cell will not produce or respond to mating pheromones, and when starved, the cell will unsuccessfully attempt to undergo meiosis with fatal results.[21] Similarly, deletion of one copy of theMAT locus in a diploid cell, leaving either aMATa orMATα allele, will cause a diploid cell to behave like a haploid cell of the associated mating type.[22][23]
α cells with inactivatedα1 andα2 genes at theMAT locus will exhibit the mating behavior ofa cells. When ana-like faker (alf) cell mates with an α cell, they form a diploid cell lacking an active copy of thea1 gene. As a result, these diploid cells cannot form thea1-α2 protein complex needed to repress haploid-specific genes. This diploid cell will act like a haploid α cell, producing α pheromones to mate with ana haploid cell, resulting inaneuploidy.[24]
Since α cells do not ordinarily mate with each other, the presence ofa-like faker cells in a population of α cells can be detected in ana-like faker assay. This test exposes theMATα population, which lacks an active copy of theHIS3 gene, to a tester strain like YPH316 yeast, which lack aHIS1 gene, onYEPDagar. After transferring the pairs of yeast strains ontoSabouraud agar, only those that formed diploid cells by havinga-like faker cells mate with the tester strain will be capable of synthesizing theamino acidhistidine to survive. The extent ofchromosome instability can be inferred from the proportion of surviving pairs sincea-like faker cells naturally arise from damage to Chromosome III in yeast cells.[25]
Mating in yeast is stimulated bya cells'a-factor or α cells' α-factor pheromones binding the Ste3 receptor of α cells or Ste2 receptor ofa cells, respectively, activating aheterotrimeric G protein.[26][27][28] The dimeric portion of this G-protein recruits Ste5 and itsMAPKcascade to themembrane, resulting in the phosphorylation ofFus3.[29]
The switching mechanism arises as a result of competition between the Fus3 protein (a MAPK protein) and thephosphatasePtc1.[30] These proteins both attempt to control the four phosphorylation sites ofSte5, ascaffold protein, with Fus3 attempting to phosphorylate the phosphosites and Ptc1 attempting to dephosphorylate them.[31]
Presence of α-factor induces recruitment of Ptc1 to Ste5 via a four-amino acid motif located within the Ste5 phosphosites.[32] Ptc1 then dephosphorylates Ste5, resulting in the dissociation of the Fus3-Ste5 complex.[33] Fus3 dissociates in a switch-like manner, dependent on the phosphorylation state of the four phosphosites.[34] All four phosphosites must be dephosphorylated in order for Fus3 to dissociate.[35][36] Fus3's ability to compete with Ptc1 decreases as Ptc1 is recruited, and thus the rate of dephosphorylation increases with the presence of pheromone.[37]
Kss1, a homologue of Fus3, does not affect shmooing, and does not contribute to the switch-like mating decision.[38][39]
In yeast, mating as well as the production of shmoos occur via an all-or-none, switch-like mechanism.[40] This switch-like mechanism allows yeast cells to avoid making an unwise commitment to a highly demanding procedure.[41] The decision to mate must balance being energy-conservative and fast enough to avoid losing the potential mate.[42]
Yeast maintain an ultra-sensitivity to mating through:
Multi-site phosphorylation – Fus3 only dissociates from Ste5 and becomes fully active when all four of the phosphosites are dephosphorylated. Even one phosphorylated site will result in immunity to α-factor.[43]
Two-stage binding – Fus3 and Ptc1 bind to separate docking sites on Ste5. Only after docking can they act on the phosphosites.[44]
Steric hindrance – competition between Fus3 and Ptc1 to control the four phosphosites on Ste3
a and α yeast share the same mating response pathway, with the only difference being the type of receptor that each mating type possesses.[45] Thus, the above description of ana-type yeast stimulated with α-factor resembles the mechanism of an α-type yeast stimulated with a-factor.[46][47]
A haploid yeast dividing and undergoing a mating type switch, allowing mating and diploid formation.
Wild type haploid yeast are capable of switching mating type betweena and α.[48] Consequently, even if a single haploid cell of a given mating type founds acolony of yeast, mating type switching will cause cells of botha and α mating types to be present in the population.[49][50] Combined with the strong drive for haploid cells to mate with cells of the opposite mating type and form diploids, mating type switching and consequent mating will cause the majority of cells in a colony to be diploid, regardless of whether a haploid or diploid cell founded the colony.[51] The vast majority of yeaststrains studied inlaboratories have been altered such that they cannot perform mating type switching (by deletion of theHO gene; see below). This allows the stable propagation of haploid yeast, as haploid cells of thea mating type will remaina cells (and α cells will remain α cells), unable to form diploid cells unless artificially exposed to the other mating type.[52]
Location of the silentHML andHMR loci and the activeMAT locus on yeast chromosome III
Haploid yeast switch mating type by replacing the information present at theMAT locus.[53] For example, ana cell will switch to an α cell by replacing theMATa allele with theMATα allele.[54] This replacement of one allele ofMAT for the other is possible because yeast cells carry an additionalsilenced copy of both theMATa andMATα alleles: theHML (homothallicmatingleft) locus typically carries a silenced copy of theMATα allele, and theHMR (homothallicmatingright) locus typically carries a silenced copy of theMATa allele.[7] The silentHML andHMR loci are often referred to as the silent mating cassettes, as the information present there is 'read into' the activeMAT locus.[55]
These additional copies of the mating type information do not interfere with the function of whatever allele is present at theMAT locus because they are not expressed, so a haploid cell with theMATa allele present at the activeMAT locus is still ana cell, despite also having a silenced copy of theMATα allele present atHML.[56] Only the allele present at the activeMAT locus is transcribed, and thus only the allele present atMAT will influence cell behaviour.[6] Hidden mating type loci are epigenetically silenced bySIR proteins, which form aheterochromatin scaffold that prevents transcription from the silent mating cassettes.[57]
The process of mating type switching is agene conversion event initiated by theHO gene.[58] TheHO gene is a tightly regulated haploid-specific gene that is only activated in haploid cells during theG1 phase of thecell cycle.[59] Theprotein encoded by theHO gene is aDNA endonuclease, which physically cleaves DNA, but only at theMAT locus (due to the DNA sequence specificity of the HO endonuclease).[60]
Once HO cuts the DNA atMAT,exonucleases are attracted to the cut DNA ends and begin to degrade the DNA on both sides of the cut site.[61] This DNA degradation by exonucleases eliminates the DNA which encoded theMAT allele; however, the resulting gap in the DNA isrepaired by copying in the genetic information present at eitherHML orHMR, filling in a new allele of either theMATa orMATα gene. Thus, the silenced alleles ofMATa andMATα present atHML andHMR serve as a source of genetic information to repair the HO-induced DNA damage at the activeMAT locus.[7]
The repair of theMAT locus after cutting by the HO endonuclease almost always results in a mating type switch.[7][60] When ana cell cuts theMATa allele present at theMAT locus, the cut atMAT will almost always be repaired by copying the information present atHML.[6] This results inMAT being repaired to theMATα allele, switching the mating type of the cell froma to α.[62] Similarly, an α cell which has itsMATα allele cut by the HO endonuclease will almost always repair the damage using the information present atHMR, copying theMATa gene to theMAT locus and switching the mating type of α cell toa.[63]
This is the result of arecombination enhancer (RE) located on the left arm of chromosome III.[64] Normally,a cells haveMcm1 bind to the RE to promote recombination using the HML region.[65] Deletion of the RE causesa cells to instead repair using HMR, maintaining their status asa cells rather than switching mating types.[66] In α cells, the α2 factor binds at the RE to repress recombination using the HML region.[67] Thus, yeast have a predetermined tendency toward DNA repair of theMAT locus using the HMR region.[68]
In 2006, evolutionary geneticistLeonid Kruglyak found thatS. cerevisiae matings only involve out-crossing between different strains roughly once every 50,000 cell divisions. The vast majority of yeast mating instead involves members of the same strain because mating type switching allows a singleascus to produce both mating types from a single haploid cell.[69] This suggests that yeast primarily maintain their capability to mate through recombinational DNA repair during meiosis, rather thannatural selection forfitness among a population with highgenetic variability.[70]
Schizosaccharomyces pombe is a facultative sexual yeast that can undergo mating when nutrients are limited.[71] Exposure ofS. pombe tohydrogen peroxide, which causesoxidative stress toDNA, strongly induces mating, meiosis, and formation of meiotic spores.[72] Thus, meiosis and meiotic recombination may be an adaptation for repairing DNA damage.[73] TheMAT locus' structure inS. pombe resemblesS. cerevisiae. The mating-type switching system is similar but evolved independently.[6]
Cryptococcus neoformans is abasidiomycetous fungus that grows as a budding yeast in culture and infected hosts.C. neoformans causes life-threateningmeningoencephalitis in immunocompromised patients. It undergoes a filamentous transition during the sexual cycle to produce spores, the suspected infectious agent. The vast majority of environmental and clinical isolates ofC. neoformans are of mating type α. Filaments ordinarily have haploid nuclei, but these can undergo a process of diploidization (perhaps byendoreduplication or stimulated nuclear fusion) to form diploid cells termedblastospores.[74]
The diploid nuclei of blastospores can then undergo meiosis, including recombination, to form haploidbasidiospores that can then be dispersed.[74] This process is referred to as monokaryotic fruiting. This process depends on the genedmc1, a conserved homologue of the bacterialRecA and eukaryoticRAD51 genes.Dmc1 mediates homologous chromosome pairing during meiosis and repair ofdouble-strand breaks in DNA.[75] Meiosis inC. neoformans may be performed to promote DNA repair in DNA-damaging environments, such as host-mediated responses to infection.[74]
^For the sake of clarity, this article bolds the Latin letter "a" and uses regularfont weight for the Greek α. The usual convention is to print both in the same weight, but doing so would make the two letters hard to tell apart initalicized text.
^Lee CS, Haber JE (April 2015). Gellert M, Craig N (eds.). "Mating-type Gene Switching in Saccharomyces cerevisiae".Microbiology Spectrum.3 (2): MDNA3–0013–2014.doi:10.1128/microbiolspec.MDNA3-0013-2014.PMID26104712.
^Ruderfer DM, Pratt SC, Seidel HS, Kruglyak L (September 2006). "Population genomic analysis of outcrossing and recombination in yeast".Nature Genetics.38 (9):1077–1081.doi:10.1038/ng1859.PMID16892060.S2CID783720.
^Birdsell JA, Wills C (2003). "The evolutionary origin and maintenance of sexual recombination: A review of contemporary models.". In MacIntyre RJ, Clegg MT (eds.).Evolutionary Biology. Evolutionary Biology Series. Vol. 33. Springer. pp. 27–137.ISBN978-0306472619.
