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. 1999 Aug 17;96(17):9721-6.
doi: 10.1073/pnas.96.17.9721.

Systematic changes in gene expression patterns following adaptive evolution in yeast

T L Ferea  1 , D Botstein, P O Brown, R F Rosenzweig
Affiliations

Systematic changes in gene expression patterns following adaptive evolution in yeast

T L Ferea et al. Proc Natl Acad Sci U S A. .

Abstract

Culturing a population of Saccharomyces cerevisiae for many generations under conditions to which it is not optimally adapted selects for fitter genetic variants. This simple experimental design provides a tractable model of adaptive evolution under natural selection. Beginning with a clonal, founding population, independently evolved strains were obtained from three independent cultures after continuous aerobic growth in glucose-limited chemostats for more than 250 generations. DNA microarrays were used to compare genome-wide patterns of gene expression in the evolved strains and the parental strain. Several hundred genes were found to have significantly altered expression in the evolved strains. Many of these genes showed similar alterations in their expression in all three evolved strains. Genes with altered expression in the three evolved strains included genes involved in glycolysis, the tricarboxylic acid cycle, oxidative phosphorylation, and metabolite transport. These results are consistent with physiological observations and indicate that increased fitness is acquired by altering regulation of central metabolism such that less glucose is fermented and more glucose is completely oxidized.

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Figures

Figure 1
Figure 1
Graphical representations of the differences in transcript abundance between the evolved strains and the parental strain for the 88 functionally characterized genes whose transcripts differed by at least 2-fold on two or more microarrays. The ratio of transcript levels in the evolved strain compared with the parental strain, measured for each gene, is represented by the color of the corresponding box in this graphical display (see scale). Red represents a higher level of expression in the evolved strain, and green represents a higher level of expression in the parental strain. The color saturation represents the magnitude of the expression ratio, as indicated by the scale at the bottom of the figure. Black indicates no detectable difference in expression levels; gray denotes a missing observation. (a) Hierarchical clustering of gene expression. Relationships in expression patterns among the genes are represented by the tree at the left of the display, with branch lengths indicative of the magnitude of the differences between gene expression patterns (16). (b) Expression patterns organized according to functionally defined categories.
Figure 2
Figure 2
(a) Alterations in gene expression consistent in two or more experiments are projected onto metabolic maps of central carbon metabolism. Increases (red) and decreases (green) of 2-fold or greater in transcripts encoding the enzymes that mediate the steps in these pathways are represented by the color of the corresponding box. (b) Average expression ratios for sets of genes encoding the mitochondrial protein complexes involved in oxidative phosphorylation. The expression ratios for COX5B, the differentially expressed isozyme of COX5A, are indicated separately from the other components of cytochrome c oxidase complex.
Figure 3
Figure 3
Cells were cultured aerobically in the chemostat at 30°C with glucose limitation (0.08%), harvested, and fixed in formaldehyde. Cells were stained with DAPI and photographed with a Delta Vision microscope (Applied Imaging Systems) to compare the abundance of mitochondrial DNA in the parental and evolved strains. (A) Parental strain. (B, C, and D) Isolates from the three evolved populations E1, E2, and E3, respectively.
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