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Biomedical subjects

T L Ferea

Publications and source records attributed to T L Ferea.

3 recordsLinked to original sources

Systematic changes in gene expression patterns following adaptive evolution in yeast.

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.

Adaptation, Physiological↗

Observing the living genome.

Dynamic pictures of living genomes are now beginning to emerge from systematic studies of gene expression patterns using DNA microarrays. The rich information represented in the variation in each gene's expression provides the basis for a new kind of genomic map.

Animals↗

The vacuolar ATPase of Neurospora crassa is indispensable: inactivation of the vma-1 gene by repeat-induced point mutation.

To analyze the phenotype of cells lacking the vacuolar ATPase, we inactivated the vma-1 gene, which encodes the catalytic subunit of the enzyme. Because preliminary experiments suggested the vma-1 gene was essential, we developed a method of simultaneously inactivating the gene and complementing it with a functional copy. We call this method repeat-induced point mutation (RIP) & Rescue. Two strains, both of which contained an extra copy of the vma-1 gene, were mated. Progeny that had inherited a functional copy of the gene at an ectopic site in the genome were selected. In some of these progeny the endogenous vma-1 gene had been altered by the RIP process. Sequencing showed the endogenous vma-1 gene had been inactivated by multiple point mutations. Progeny from strains with an inactive endogenous vma-1 gene were inviable unless a functional copy of the gene cosegregated, indicating that the vacuolar ATPase is essential in Neurospora crassa.

Base Sequence↗