Academic journal article Genetics

Yeast: An Experimental Organism for 21st Century Biology

Academic journal article Genetics

Yeast: An Experimental Organism for 21st Century Biology

Article excerpt

ABSTRACT In this essay, we revisit the status of yeast as a model system for biology. We first summarize important contributions of yeast to eukaryotic biology that we anticipated in 1988 in our first article on the subject. We then describe transformative developments that we did not anticipate, most of which followed the publication of the complete genomic sequence of Saccharomyces cerevisiae in 1996. In the intervening 23 years it appears to us that yeast has graduated from a position as the premier model for eukaryotic cell biology to become the pioneer organism that has facilitated the establishment of the entirely new fields of study called "functional genomics" and "systems biology." These new fields look beyond the functions of individual genes and proteins, focusing on how these interact and work together to determine the properties of living cells and organisms.

TWENTY-THREE years ago, in an article in Science magazine, we speculated that yeast might be the ideal experimental organism for modern biology. We argued that the amalgam of recombinant DNA technology and classical biochemistry and genetics had created a revolution that gave biologists access to an array of new methods for connecting proteins and genes with their roles in the biology of an organism. We wrote that the reason that yeast could serve "as a model for all eukaryotic biology derives from the facility with which the relation between gene structure and protein function can be established" (Botstein and Fink 1988, p. 1440).

In this essay, we revisit the status of yeast as a model experimental system. We begin by providing a summary of the important contributions of yeast to the knowledge of eukaryotic biology that we anticipated in 1988. We then describe transformative developments that we did not anticipate, most of which followed the publication of the complete genome sequence of Saccharomyces cerevisiae in April 1996. We have made no effort to provide a formal review of the literature. The articles that we cite are intended as illustrative examples only.

In the 23 years since our last essay it appears to us that yeast has graduated from a position as the premier model for eukaryotic cell biology to become the pioneer organism that facilitated the establishment of entirely new fields of study called "functional genomics" and "systems biology." These new fields look beyond the functions of individual genes and proteins, focusing on how they interact and work together to determine the properties of living cells and organisms.

Functional Genomics: Gene-Protein-Function Association via Mutants

Probably the most important and enduring contribution of the model yeasts (S. cerevisiae and Schizosaccharomyces pombe) and the scientific communities that study the biology of these organisms has been the connection of genes and proteins with the functions that they provide to cells. As we indicated in 1988, the methods for introducing mutations, at will, into and out of the yeast genome, have made it particularly easy to study not only the biochemical function of gene products, but also the biological consequences of failure of the genes to function. Mutations were produced and introduced into yeast strains by each researcher as needed; this soon came to be seen as rate limiting.

Not long after the publication of the yeast genome sequence, the Saccharomyces community organized a cooperative effort that produced a nearly complete set of deletions of every open reading frame (cf. Winzeler et al. 1999 and Giaever et al. 2002). Each gene was replaced by a drugresistance gene and marked with synthetic "barcode" sequences. These features made each deletion selectable, facilitating transfer by DNA transformation, and made each deletion distinguishable from all the others so that individual mutants can be followed in screens of the entire library of deletion mutants. Mutations in each yeast gene and many ensembles of mutations have been subjected to diverse biological assays, often leading to increased understanding of the biological roles of many of the genes. …

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