Schizosaccharomyces pombe

Schizosaccharomyces pombe, also called "fission yeast", is a species of yeast. It is used as a model organism in molecular and cell biology. It is a unicellular eukaryote, whose cells are rod-shaped. Cells typically measure 3 to 4 micrometres in diameter and 7 to 14 micrometres in length. Its genome, which is approximately 14.1 million base pairs, is estimated to contain 4,970 protein-coding genes and at least 450 non-coding RNAs.

These cells maintain their shape by growing exclusively through the cell tips and divide by medial fission to produce two daughter cells of equal sizes, which makes them a powerful tool in cell cycle research.

Fission yeast was isolated in 1893 by Lindner from East African millet beer. The species name is derived from the Swahili word for beer (Pombe). It was first developed as an experimental model in the 1950s: by Urs Leupold for studying genetics, and by Murdoch Mitchison for studying the cell cycle.

The fission yeast researcher Paul Nurse successfully merged the independent schools of fission yeast genetics and cell cycle research. Together with Lee Hartwell and Tim Hunt, Nurse won the 2001 Nobel Prize in Physiology or Medicine for their work on cell cycle regulation.

The sequence of the S. pombe genome was published in 2002, by a consortium led by the Sanger Institute, becoming the sixth model eukaryotic organism whose genome has been fully sequenced. This has fully unlocked the power of this organism, with many genes homologous to human disease genes being identified. In 2006, sub-cellular localization of all the proteins in S. pombe was published using green fluorescent protein as a molecular tag.

S. pombe has also become an important organism in studying the cellular responses to DNA damage and the process of DNA replication.

Approximately 120 natural strains of S. pombe have been isolated. These have been collected from a variety of locations including Europe, North and South America and Asia. The majority of these strains have been collected from cultivated fruits such as apples and grapes, or from the various alcoholic beverages, such as Brazilian Cachaça. It is not clear at present whether S. pombe is the major fermenter or a contaminant in such brews. The natural ecology of Schizosaccharomyces yeasts is not well studied.

Comparison with budding yeast (Saccharomyces cerevisiae)
The yeast species S. pombe and S. cerevisiae are both extensively studied; these two species diverged approximately 300 to 600 million years before present, and are significant tools in molecular and cellular biology. Some of the technical discriminants between these two species are:


 * S. cerevisiae has approximately 5,600 open reading frames; S. pombe has approximately 4,970 open reading frames.
 * Despite similar gene numbers, S. cerevisiae has only about 250 introns, while S. pombe has nearly 5,000.
 * S. cerevisiae has 16 chromosomes, S. pombe has 3.
 * S. cerevisiae is often diploid while S. pombe is usually haploid.
 * S. cerevisiae is in the G1 phase of the cell cycle for an extended period (consequently, G1-S transition is tightly controlled) while S. pombe remains in the G2 phase of the cell cycle for an extended period (consequently, G2-M transition is under tight control).
 * Both species share genes with higher eukaryotes that they do not share with each other. S. pombe has RNAi machinery genes like those in vertebrates, while this is missing from S. cerevisiae. S. cerevisiae also has greatly simplified heterochromatin compared to S. pombe. Conversely, S. cerevisiae has well-developed peroxisomes, while S. pombe does not.
 * S. cerevisiae has small point centromere of 125 bp, and sequence-defined replication origins of about the same size. Conversely, S. pombe has large, repetitive centromeres (40–100 kb) more similar to mammalian centromeres, and degenerate replication origins of at least 1kb.

Life cycle
The fission yeast is a single-celled fungus with simple, fully characterized genome and a rapid growth rate. It has long since been used in brewing, baking and molecular genetics. S. pombe is a rod-shaped cell, approximately 3 µm in diameter, that grows entirely by elongation at the ends. After mitosis, division occurs by the formation of a septum, or cell plate, that cleaves the cell at its midpoint.

The central events of cell reproduction are chromosome duplication, which takes place in S (Synthetic) phase, followed by chromosome segregation and nuclear division (mitosis) and cell division (cytokinesis), which are collectively called M (Mitotic) phase.G1 is the gap between M and S phases, and G2 is the gap between S and M phases. In the budding yeast, the G2 phase is particularly extended, and cytokinesis (daughter-cell segregation) does not happen until a new S (Synthetic) phase is launched.

Fission yeast governs mitosis by mechanisms that are similar to those in multicellular animals. It normally proliferates in a haploid state. When starved, cells of opposite mating types (P and M) fuse to form a diploid zygote that immediately enters meiosis to generate four haploid spores. When conditions improve, these spores germinate to produce proliferating haploid cells.

Cytokinesis in fission yeast
The general features of cytokinesis are shown here. The site of cell division is determined before anaphase. The anaphase spindle (in green on the figure) is then positioned so that the segregated chromosomes are on opposite sides of the predetermined cleavage plane.

Size control in fission yeast
In fission yeast, where growth governs progression through G2/M, a wee1 mutation causes entry into mitosis at an abnormally small size, resulting in a shorter G2. G1 is lengthened, suggesting that progression through Start (beginning of cell cycle) is responsive to growth when the G2/M control is lost. Furthermore, cells in poor nutrient conditions grow slowly and therefore take longer to double in size and divide. Interestingly enough, low nutrient levels also reset the growth threshold so that cell progresses through the cell cycle at a smaller size. Finally, wee1 mutant fission yeast cells are smaller than wild-type cells, but take just as long to go through the cell cycle. This is possible because small yeast cells grow slower, that is, their added total mass per unit time is smaller than that of normal cells.

A spatial gradient is thought to coordinate cell size and mitotic entry in fission yeast. The Pom1 protein kinase (green) is localized to the cell cortex, with the highest concentration at the cell tips. The cell-cycle regulators Cdr2, Cdr1 and Wee1 are present in cortical nodes in the middle of the cell (blue and red dots). a, In small cells, the Pom1 gradient reaches most of the cortical nodes (blue dots). Pom1 inhibits Cdr2, preventing Cdr2 and Cdr1 from inhibiting Wee1, and allowing Wee1 to phosphorylate Cdk1, thus inactivating cyclin-dependent kinase (CDK) activity and preventing entry into mitosis. b, In long cells, the Pom1 gradient does not reach the cortical nodes (red dots), and therefore Cdr2 and Cdr1 remain active in the nodes. Cdr2 and Cdr1 inhibit Wee1, preventing phosphorylation of Cdk1 and thereby leading to activation of CDK and mitotic entry. (This simplified diagram omits several other regulators of CDK activity.)

Mating-type switching in fission yeast
Fission yeast switches mating type by a replication-coupled recombination event, which takes place during S phase of the cell cycle. Fission yeast uses intrinsic asymmetry of the DNA replication process to switch the mating type; it was the first system, where the direction of replication was shown to be required for the change of the cell type. Studies of the mating-type switching system lead to a discovery and characterization of a site-specific replication termination site RTS1, a site-specific replication pause site MPS1, and a novel type of chromosomal imprint, marking one of the sister chromatids at the mating-type locus mat1. In addition, work on the silenced donor region has led to great advances in understanding formation and maintenance of heterochromatin.


 * Pombe Pages
 * Pombe Gene Database
 * Pombe Genome at the Sanger Centre
 * Yeast Resource Center
 * European Bioinformatics Institute
 * Wiley's Journal Yeast
 * Fission Yeast - a Model Worthy of Pursuit