In yeast genetics

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“Genetics is, therefore, one of a trio of methods, the others being molecular biology/biochemistry and cell biology, which are required to understand the function of individual genes in vivo”

                         Susan L. Forsburg

Yeast geneticists half-mockingly talk about the cult of APYG: the ‘awesome power of yeast genetics’. But mocking aside, these simple, single-celled fungi have proven themselves to be the workhorses of cell biology because of the ease of their genetic manipulation. The budding yeast Saccharomyces cerevisiae and the fission yeast Schizosaccharomyces pombe are quite different in their biology (FIG. 1), but they share a similar tool set that makes the process of gene discovery, and subsequent characterization of gene function, remarkably easy.

 Historically, S. cerevisiae has been the more popular experimental system. The first eukaryote to be transformed by plasmids, it was also the first eukaryote for which precise gene knockouts were constructed, and the first to have its genome sequenced1–3. The cell biological issues that have been explored in this ASCOMYCETE range from signal transduction to cell-cycle control, chromosome structure to secretion. The identified genes have been used as probes to uncover further pathways and to identify metazoan homologues. Despite the completion of its genome sequence several years ago1 , the roles of many of its 6,000+ genes remain unclear. The process of mutant analysis and discovery of gene function continues with the added tools of genomics4,5. By contrast, the experimental history of S. pombe involves a smaller, but growing, community. Its genome sequence is essentially complete but shares no conserved synteny (gene order) with the budding yeast in its 4,900+ genes6 . Although yeast phylogeny is still unclear, S. pombe is thus quite distinct from S. cerevisiae and filamentous fungi7–9. The fission yeast has a symmetrical pattern of cell division and has been particularly popular for studies of cell growth and division, and chromosome dynamics. Other cell biological questions have been addressed more recently, inspired by the power of a comparative approach between these two superficially similar organisms. Each of them offers unique insights as a model organism for elucidating the biology of more complex cell types10. Both yeasts are adaptable to several forms of genetic analysis that allow the identification of new genes, or the functional analysis of previously identified genes11,12. Because both can grow and divide as haploids, recessive mutations are easily recovered. However, a diploid sexual cycle exists for both, allowing facile genetic analysis, including tests of COMPLEMENTATION, RECOMBINATION and EPISTASIS. The identification of replication origin sequences allows plasmids to be maintained as free episomes, and these are easily introduced into the cell by transformation. In addition, both species have high rates of homologous recombination, allowing precise manipulation of the genome for the construction of gene disruptions and allele-specific replacements. Their nomenclature is distinct, but they benefit from similar genetic and molecular tools, which provide the basic requirements for the genetic screens described below. With the genome sequences of both species now completed, the challenge is to identify the functions associated with their genes. The classical genetic analysis described here complements the newest genomic approaches13: genetics moves from a function, defined by mutation, to identify the gene responsible, whereas genomics moves from the catalogue of genes to identify their function. The true power of genetics is its predictive value; genetic interactions predict physical interactions, and these can be tested using standard molecular and biochemical techniques. Genetics is, therefore, one of a trio of methods, the others being molecular biology/biochemistry and cell biology, which are required to understand the function of individual genes in vivo.

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two yeast species.

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The genomics revolution complements the classical

genetics approach.

Adapted from: THE ART AND DESIGN OF GENETIC SCREENS; Susan L. Forsburg; YEAST, NATURE REVIEWS | GENETICS ; VOLUME 2 | SEPTEMBER 2001 | 659-668

Macherki M E