Proteome variation in yeast: Response to altered gene dosage

Cellular behavior is ultimately dictated by the collection of all cellular proteins, the proteome. To understand proteome variation in both wild-type and mutant cells, we have used Difference Gel Electrophoresis, a two-dimensional electrophoresis technique, to compare the protein profiles of several Saccharomyces cerevisiae strains. Three different classes of mutations were tested for proteome variation: heterozygous deletions of essential genes, heterozygous and homozygous deletions of a stress-response gene and homozygous deletions of non-essential genes. The yeast proteome was found to be very stable when separate cultures of identical strains were grown in the same media at the same time; there was considerable proteome variability when comparing identical strains grown at different times. Heterozygous mutations in both of the tested essential genes did not have any detectable protein changes, whereas loss of the stress-response gene, HSP82, was compensated by changes in other stress-response proteins. Strains that had lost a non-essential gene, which resulted in reduced growth rate, displayed extensive proteome changes. These studies demonstrate that yeast cells utilize a variety of mechanisms to compensate for genetic variation.