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Ryszard Korona

Publications and source records attributed to Ryszard Korona.

6 recordsLinked to original sources
PubMed2006

Why molecular chaperones buffer mutational damage: a case study with a yeast Hsp40/70 system.

The malfunctioning of molecular chaperones may result in uncovering genetic variation. The molecular basis of this phenomenon remains largely unknown. Chaperones rescue proteins unfolded by environmental stresses and therefore they might also help to stabilize mutated proteins and thus mask damages. To test this hypothesis, we carried out a genomewide mutagenesis followed by a screen for mutations that were synthetically harmful when the RAC-Ssb1/2 cytosolic chaperones were inactive. Mutants with such a phenotype were found and mapped to single nucleotide substitutions. However, neither the genes identified nor the nature of genetic lesions implied that folding of the mutated proteins was being supported by the chaperones. In a second screen, we identified temperature-sensitive (ts) mutants, a phenotype indicative of structural instability of proteins. We tested these for an association with sensitivity to loss of chaperone activity but found no such correlation as might have been expected if the chaperones assisted the folding of mutant proteins. Thus, molecular chaperones can mask the negative effects of mutations but the mechanism of such buffering need not be direct. A plausible role of chaperones is to stabilize genetic networks, thus making them more tolerant to malfunctioning of their constituents.

Adenosine Triphosphatases↗
PubMed2005

Loss of dispensable genes is not adaptive in yeast.

A substantial share of genes identified in yeast can be deleted without visible phenotypic effects. Current debate concentrates on the possible roles of seemingly dispensable genes. The costs of maintaining unnecessary functions has attracted little attention. The hypothesis of antagonistic pleiotropy postulates that adaptations to different constituents of the environment are likely to interfere with each other, and therefore loss of unnecessary functions is potentially advantageous. We tested an entire collection of nonessential yeast gene deletions in a benign and nutritionally rich environment in which the number of dispensable genes was particularly high. We applied a series of competition experiments that could detect differences in relative fitness of approximately 0.005. No beneficial deletions were found, except perhaps for the deletion of about a dozen genes that slightly improved competitive ability; however, a functional explanation of the fitness advantage is lacking. The paucity of beneficial gene deletions is striking because genetic adaptations to laboratory conditions are regularly observed in yeast. However, it accords with the finding that the gene contents of four species of Saccharomyces are nearly identical, despite up to 20 million years of independent evolution and extensive DNA sequence divergence. Such extreme conservation of functions would be improbable if there were periods of selection promoting the loss of temporarily dispensable genes. The evident cohesion of the yeast genomes may be their evolved feature or an intrinsic property of complex genetic systems.

Adaptation, Physiological↗
PubMed2004

Experimental studies of deleterious mutation in Saccharomyces cerevisiae.

Yeast has proven to be a very useful model organism for studying eukaryotic cell functions. Its applicability for population and quantitative genetics is less well known. Among its advantages is the ease of screening for mutants. The present paper reviews experiments aimed at estimating the parameters of spontaneous mutations deleterious to fitness. The rate of deleterious mutation was found to be moderately high. A large fraction of detectable mutants were lethal; among the non-lethal mutants, the least harmful ones dominated. Deleterious mutations, and especially the lethal ones, were generally very well masked by wild-type alleles when in heterozygous loci. The negative effects of mutations were much stronger under stressful than under benign conditions. Interactions between loci with deleterious mutations did alter their fitness, but no strong overall effect of synergism or antagonisms was observed.

Alleles↗
PubMed2004

Mutational load and the transition between diploidy and haploidy in experimental populations of the yeast Saccharomyces cerevisiae.

Mutations were accumulated over hundreds of generations in a mutator strain of yeast in a constant laboratory environment. This ensured that mutations were frequent and that the quality of environment remained unchanged. Mutations were accumulated in asexual populations of diploids but their impact on fitness was tested both for the diploid clones and for haploid clones derived from them. Dozens of harmful and lethal mutations accumulated in diploids, but important phenotypic traits, such as maximum growth rate, did not deteriorate by more than 10%. There were no signs of decline in population size. In strong contrast, the populations of haploids derived from the diploids suffered from high mortality; their density was reduced by more than three orders of magnitude. These findings indicate how ineffective natural selection can be in removing deleterious mutations from populations of clonally reproducing diploids. They also suggest that phenotypic assays of heterozygous diploids may be of little value as indicators of increasing genetic degeneration.

Genetics, Population↗
PubMed2003

Small fitness effects and weak genetic interactions between deleterious mutations in heterozygous loci of the yeast Saccharomyces cerevisiae.

Rare, random mutations were induced in budding yeast by ethyl methanesulfonate (EMS). Clones known to bear a single non-neutral mutation were used to obtain mutant heterozygotes and mutant homozygotes that were later compared with wild-type homozygotes. The average homozygous effect of mutation was an approximately 2% decrease in the growth rate. In heterozygotes, the harmful effect of these relatively mild mutations was reduced approximately fivefold. In a test of epistasis, two heterozygous mutant loci were paired at random. Fitness of the double mutants was best explained by multiplicative action of effects at single loci, with little evidence for epistasis and essentially excluding synergism. In other experiments, the same mutations in haploid and heterozygous diploid clones were compared. Regardless of the haploid phenotypes, mildly deleterious or lethal, fitness of the heterozygotes was decreased by less than half a per cent on average. In general, the results presented here suggest that most mutations tend to exhibit small and weakly interacting effects in heterozygous loci regardless of how harmful they are in haploids or homozygotes.

Clone Cells↗