Yeast Genetics and Molecular Biology 1998
College Park, Maryland
August 1998


Name: Rosenzweig, Frank
Mailing Address: Biological Sciences, University of Idaho, 265 Life Sciences, Moscow, ID 83844-3051, United States
Email Address: rrose@uidaho.edu
Phone and Fax numbers: 208-885-7764, 208-885-7905

059

Functional analysis of the yeast genome by DNA microarray hybridization after evolution in a simple defined environment.


Tracy Ferea, David Botstein (1), Patrick Brown (2), Frank Rosenzweig (3)
(1) Department of Genetics, Stanford University School of Medicine, Stanford CA; (2) Department of Biochemistry and HHMI, Stanford University School of Medicine, Stanford CA; (3) Biological Sciences, University of Idaho, 265 Life Sciences, Moscow, ID 83844-3051, United States

The completion of the yeast genome project, coupled with the development of DNA microarray hybridization technology, opens up unprecedented opportunities for the study of evolution in action. We have conducted replicate evolutionary experiments wherein a diploid yeast strain was propagated asexually for several hundred generations under glucose-limitation.Under these conditions new adaptive mutants sweep through populations approximately every fifty generations.Evolved strains demonstrate significantly higher fitness than their common ancestor. Using microarrays we have analyzed changes in mRNA levels that distinguish ancestral from evolved strains. Replicate short-term chemostat monocultures of each strain are highly consistent in their global patterns of gene expression. By contrast, comparisons of ancestral to experimentally evolved strains show significant differences with respect to a limited set of genes. Perhaps more strikingly, these comparisons reveal that similar changes have occurred within a subset of genes that encode enzymes of glycolysis and the TCA cycle. Patterns of gene expression at these loci have enabled us to accurately predict the outcome of comparisons between strains with respect to yield biomass, cell number and steady-state levels of specific metabolites. Lineages derived from a common ancestor may follow independent adaptive trajectories, yet nevertheless converge on a common physiological phenotype. Given that a limited number of periodic selection events have occurred, it appears that regulatory loci responsible for coordinate changes in expression within specific pathways are key targets of selection as yeast evolve under nutrient limitation.


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