Survey of Genomes - Schizosaccharomyces pombe

In this episode from the survey of genomes, Brett Bentkowski from the 2019 Hiram College Genetics course introduces us to the unicellular eukaryote Schizosaccharomyces pombe, also called a fission yeast. It is a model system for understanding the cell cycle.

Welcome to Genomics Revolution. I am Brett Bentkowski, from the 2019 Hiram College Genetics Course and it is my pleasure to host this episode on Schizosaccharomyces pombe, the so called fission yeast. Fission yeast was first reported in 1893, by Paul Lindner, who isolated if from East African millet beer. It gets its species name pombe from the Swahili word for beer: pombe. It then went on to be used by Urs Leupold for genetic study, and then by Murdoch Mitchison for studying the cell cycle, both around the 1950s. S. pombe’s common name, fission yeast, comes from how the cell divides: it grows at the cell tips and then divides by medial fission, so that two identical and equal daughter cells are created. This physical consistency makes it easy to see why it was a good model organism, and why it was an excellent choice to be the sixth genome sequenced.
 
Specifically, we’re working with the 972h- strain here, though there are approximately 160 natural strains. The sequence of fission yeast was reported in Nature in 2002, making it the sixth eukaryotic genome to ever be sequenced. It was preceded by some of our other friends in the genetics world, including Saccharomyces cerevisiae (another useful yeast species) and Drosophila melanogaster (the fruit fly). The Wellcome Trust Sanger Institute and thirteen other laboratories made up the S. pombe European Sequencing Consortium, or EUPOM, which sequenced the genome with a 100 kb sequence generated by the Cold Spring Harbor Laboratory. Sequencing was carried out by integrating two pre-existing restriction maps. These maps both contained chimaeric clones, gaps, and inserted elements, so they were problematic. In order to sequence the genome completely, DNA fragments were cloned into M13 bacteriophage (for analysis in E. coli) or cloned into pUC18 plasmids to analyze in other organisms. Random subclones were then sequenced, and Phrap or Gap4 softwares were used for contiguous assembly, using overlapping segments to generate a map of the whole genome. All of the sequences were collected centrally and checked for error by looking for frameshifts in coding regions. There were less than 1/180000 bp errors, and all of those have been resolved except for four. The sequence predicts a maximum of 4824 protein encoding genes spread over three chromosomes, for a total of 13.8 mega-base pairs (1). This organism has a high level of consistency within itself and its daughters, and the fact that it divides into two identical and equal parts makes it an excellent model organism to study the cell cycle.
 
​In humans, the Cytochrome P450 enzymes are integral in phase I metabolism of drugs. A 2013 study by Neunzig et al. expounds on a previous finding that the S. pombe genome can be used to synthesize these enzymes by recombinantly expressing the human gene in the yeast. They transformed P450 enzymes into yeast and measured 7 different human enzyme activity with coexpression of human oxidoreductases, the homologous oxidoreductase in yeast, and one oxidoreductasefrom a plant, bishop’s weed. The coexpression from the yeast oxidoreductase was found to be equally helpful for two P450 enzymes and more helpful for one other P450 enzyme (2). This shows that the S. pombe genome has biosynthetic components that are useful in humans, paving the way for metabolic treatments and therapies using other organism’s genomes.
 
​Another discovery from S. pombe is how the body uses zinc. Zinc is a co-factor for over 300 enzymes, but in higher eukaryotes there is no known indicator for zinc deficiency, since the human genome is so large and complex. Fission yeast has a gene called alcohol dehydrogenase 4, which is regulated by zinc. A study done at the Ohio State University finds that this gene is transcriptionally regulated by zinc presence or deficiency. The gene has zinc responsive elements that are regulated at the transcriptional level (3). This discovery puts us on a path to understanding human gene regulation, since now geneticists know what a sequence that is regulated by zinc looks like in a species with many human analogues.
 
​We can even use fission yeast to determine how a cell responds to damage. Another study worked with RAD9, which controls a human cell-cycle checkpoint protein was used in fission yeast to figure out how DNA damage can induce apoptosis. Fission yeast and humans have very similar RAD9 structures and mechanisms, and this homology allows us to use yeast as a model organism for humans. It turns out that RAD9 can be blocked by Bcl-2 family proteins and may have a role in regulating apoptosis after damage in addition to already known checkpoint control function (4). This is just one more example of how the S. pombe genome can contribute to human medicine and how we understand the body.
 
​The story of S. pombe has come a long way from being a beer producer to being one of the first eukaryotes sequenced to being a key player in medical research and human innovation. From apoptotic regulation, to transcriptional regulation, to metabolism, Schizosaccharomyces pombe is living up to its status as a great model organism.
 
 
 1. Wood, V., Gwilliam, R., & Rajandream, M.-A. (2002). The genome sequence of ​​​Schizosaccharomycespombe. Nature, 415(6874), 871–880. ​​​​​https://doi.org/10.1038/nature724
2. Neunzig, I., Hehn, A., Bourgaud, F., Bureik, M., Widjaja, M., Peters, F. T., & Maurer, H. H.   ​(2013). Coexpression of CPR from Various Origins Enhances Biotransformation Activity​of Human CYPs in S. pombe [electronic resource]. Applied Biochemistry and ​​​Biotechnology, 170(7), 1751–1766. https://doi.org/http://dx.doi.org/10.1007/s12010-013-​0303-2
3. Jenkins, B. (2012). Mapping zinc-responsive elements in schizosaccharomyces pombe. ​​[Columbus] : Ohio State University, 2012. Retrieved from ​​​​​​http://ezproxy.hiram.edu/login?url=http://search.ebscohost.com​/login.aspx?direct=true&db=cat01905a&AN=ohiolink.b32360643&site=eds-live
4. Komatsu, K., Miyashita, T., Hang, H., Hopkins, K. M., Zheng, W., Cuddeback, S., … Wang, ​H.-G. (2000). Human homologue of S. pombe Rad9 interacts with BCL-2/BCL-xLand ​promotes apoptosis. Nature Cell Biology, 2(1), 1. https://doi.org/10.1038/71316