Research Interests
The long-term goal of our research is to exploit budding yeast, Saccharomyces cerevisiae, as a model system for studying the mechanisms of genomic change during adaptive evolution (see "Why yeast?"). Genomes can change when a chromosome is gained or lost, resulting in aneuploidy. Aneuploid yeast strains are readily found in the laboratory (often by accident), presumably because they provide some growth advantage in a deleterious genetic background (1). However, long-term continuous cultures of nominally wild-type strains, in industry and in the lab, can also lead to the appearance of aneuploidy and chromosome rearrangements (eg, refs 2 and 3). Despite the widespread existence of aneuploidies, there is little basic information about the phenotypic effect of an extra chromosome in a wild-type genetic background, and how (or if) the aneuploidy contributes to increased fitness in long-term cultures. Are aneuploidies phenotypically neutral events in yeast? Are they deleterious? How do the gene dosage imbalances of each particular chromosome affect the phenotype? Answers to these basic questions should provide a foundation for the study and interpretation of aneuploidies arising in long-term experimental evolution cultures. In order to answer these basic questions, aneuploid strains need to be constructed in a controlled genetic background.
We wish to establish a system for studying the effects of a chromosome non-disjunction in yeast. The set of strains we construct will provide opportunities for new discovery. We will use it to ask this initial question: do the unbalanced gene dosages of N+1 aneuploids cause measurable, deleterious phenotypes in yeast?
1. Hughes, T. R., Roberts, C. J., Dai, H., Jones,
A.R., Meyer, M. R., Slade, D., Burchard, J., Dow,
S.,Ward, T. R., Kidd, M. J., et al. (2000) Nat.Genet.25,
333-337.
2. Dunham, M. J., Badrane, H., Ferea, T., Adams, J., Brown, P. O.,
Rosenzweig, F.
& Botstein, D. (2002)
Proc Natl Acad Sci U S A. 99,16144-16149.
3. Bakalinsky, A. T.
& Snow R. (1990) Yeast 6,367-382.
Support
Murdock College Research Program for Life Sciences, 2004-2006. M.J. Murdock Charitable Trust
Murdock College Research Program for Life Sciences, 2007-2009. M.J. Murdock Charitable Trust
Robert and Claire McDonald Work Award Program
Gonzaga Science Research Program
Howard Hughes Medical Institute