Extreme positive epistasis for fitness in monosomic yeast strains.

The loss of a single chromosome in a diploid organism halves the dosage of many genes and is usually accompanied by a substantial decrease in fitness. We asked whether this decrease simply reflects the joint damage caused by individual gene dosage deficiencies. We measured the fitness effects of single heterozygous gene deletions in yeast and combined them for each chromosome.

Genome-scale patterns in the loss of heterozygosity incidence in Saccharomyces cerevisiae.

Former studies have established that loss of heterozygosity can be a key driver of sequence evolution in unicellular eukaryotes and tissues of metazoans. However, little is known about whether the distribution of loss of heterozygosity events is largely random or forms discernible patterns across genomes. To initiate our experiments, we introduced selectable markers to both arms of all chromosomes of the budding yeast.

Overexpression of a single ORF can extend chronological lifespan in yeast if retrograde signaling and stress response are stimulated.

Systematic collections of single-gene deletions have been invaluable in uncovering determinants of lifespan in yeast. Overexpression of a single gene does not have such a clear outcome as cancellation of its function but it can lead to a variety of imbalances, deregulations and compensations, and some of them could be important for longevity. We report an experiment in which a genome-wide collection of strains overexpressing a single gene was assayed for chronological lifespan (CLS).

An Overexpression Experiment Does Not Support the Hypothesis That Avoidance of Toxicity Determines the Rate of Protein Evolution.

The misfolding avoidance hypothesis postulates that sequence mutations render proteins cytotoxic and therefore the higher the gene expression, the stronger the operation of selection against substitutions. This translates into prediction that relative toxicity of extant proteins is higher for those evolving faster. In the present experiment, we selected pairs of yeast genes which were paralogous but evolving at different rates.

Correction to: Gene overexpression screen for chromosome instability in yeast primarily identifies cell cycle progression genes.

In the original publication, 'Frumkin JP et al.' reference was missed to include in the reference list. The complete reference should read as below.

Gene overexpression screen for chromosome instability in yeast primarily identifies cell cycle progression genes.

Loss of heterozygosity (LOH) in a vegetatively growing diploid cell signals irregularity of mitosis. Therefore, assays of LOH serve to discover pathways critical for proper replication and segregation of chromosomes. We screened for enhanced LOH in a whole-genome collection of diploid yeast strains in which a single gene was strongly overexpressed.

Power provides protection: Genetic robustness in yeast depends on the capacity to generate energy.

The functional basis of genetic robustness, the ability of organisms to suppress the effects of mutations, remains incompletely understood. We exposed a set of 15 strains of Saccharomyces cerevisiae form diverse environments to increasing doses of the chemical mutagen EMS. The number of the resulting random mutations was similar for all tested strains.

Rapid multiple-level coevolution in experimental populations of yeast killer and nonkiller strains.

Coevolution between different biological entities is considered an important evolutionary mechanism at all levels of biological organization. Here, we provide evidence for coevolution of a yeast killer strain (K) carrying cytoplasmic dsRNA viruses coding for anti-competitor toxins and an isogenic toxin-sensitive strain (S) during 500 generations of laboratory propagation. Signatures of coevolution developed at two levels.

Comparing the rate of growth and metabolic efficiency of yeast experiencing environmental stress or genetic damage.

Physical stresses, toxic substances, and mutations can cause marked decline in the rate of growth (RG). We report that the efficiency of growth (EG), i.e.

Heterosis is prevalent among domesticated but not wild strains of Saccharomyces cerevisiae.

Crosses between inbred but unrelated individuals often result in an increased fitness of the progeny. This phenomenon is known as heterosis and has been reported for wild and domesticated populations of plants and animals. Analysis of heterosis is often hindered by the fact that the genetic relatedness between analyzed organisms is only approximately known.

Restricted pleiotropy facilitates mutational erosion of major life-history traits.

Radical shifts to new natural and human made niches can make some functions unneeded and thus exposed to genetic degeneration. Here we ask not about highly specialized and rarely used functions but those relating to major life-history traits, rate of growth, and resistance to prolonged starvation. We found that in yeast each of the two traits was visibly impaired by at least several hundred individual gene deletions.

Evaluating the fitness cost of protein expression in Saccharomyces cerevisiae.

Protein metabolism is one of the most costly processes in the cell and is therefore expected to be under the effective control of natural selection. We stimulated yeast strains to overexpress each single gene product to approximately 1% of the total protein content. Consistent with previous reports, we found that excessive expression of proteins containing disordered or membrane-protruding regions resulted in an especially high fitness cost.

Incidence of symbiotic dsRNA 'killer' viruses in wild and domesticated yeast.

Viruses are found in almost all organisms and physical habitats. One interesting example is the yeast viral 'killer system'. The virus provides the host with a toxin directed against strains that do not carry it, while the yeast cell enables its propagation.

Epistasis for growth rate and total metabolic flux in yeast.

Studies of interactions between gene deletions repeatedly show that the effect of epistasis on the growth of yeast cells is roughly null or barely positive. These observations relate generally to the pace of growth, its costs in terms of required metabolites and energy are unknown. We measured the maximum rate at which yeast cultures grow and amounts of glucose they consume per synthesized biomass for strains with none, single, or double gene deletions.

Gene dispensability.

Genome-wide mutagenesis studies indicate that up to about 90% of genes in bacteria and 80% in eukaryotes can be inactivated individually leaving an organism viable, often seemingly unaffected. Several strategies are used to learn what these apparently dispensable genes contribute to fitness. Assays of growth under hundreds of physical and chemical stresses are among the most effective experimental approaches.

Low frequency of mutations with strongly deleterious but nonlethal fitness effects.

Most experimentally detectable effects of mutations in cellular organisms are either lethal or mildly deleterious. A possible explanation for the paucity of strongly detrimental but nonlethal mutations is that the processes constituting cellular metabolism are either essential or largely redundant. Alternatively, the partition between lethal and inconspicuous mutations exists within important biological processes.

Lack of evolutionary conservation at positions important for thermal stability in the yeast ODCase protein.

Mutations destabilizing the spatial structure of proteins can persist in populations if they are fixed by drift or compensated by other mutations. The prevalence and dynamics of these processes remain largely unrecognized. A suitable target to screen for both deleterious and compensatory mutations is the URA3 gene in yeast.

Alleviation of deleterious effects of protein mutation through inactivation of molecular chaperones.

Molecular chaperones recognize and bind destabilized proteins. This can be especially important for proteins whose stability is reduced by mutations. We focused our study on a major chaperone system, RAC-Ssb, which assists folding of newly synthesized polypeptides in the yeast cytosol.

Interactions between stressful environment and gene deletions alleviate the expected average loss of fitness in yeast.

The conjecture that the deleterious effects of mutations are amplified by stress or interaction with one another remains unsatisfactorily tested. It is now possible to reapproach this problem systematically by using genomic collections of mutants and applying stress-inducing conditions with a well-recognized impact on metabolism. We measured the maximum growth rate of single- and double-gene deletion strains of yeast in several stress-inducing treatments, including poor nutrients, elevated temperature, high salinity, and the addition of caffeine.

Molecular chaperones and selection against mutations.

Background: Molecular chaperones help to restore the native states of proteins after their destabilization by external stress. It has been proposed that another function of chaperones is to maintain the activity of proteins destabilized by mutation, weakening the selection against suboptimal protein variants. This would allow for the accumulation of genetic variation which could then be exposed during environmental perturbation and facilitate rapid adaptation.

Epistatic buffering of fitness loss in yeast double deletion strains.

Interactions between deleterious mutations have been insufficiently studied, despite the fact that their strength and direction are critical for understanding the evolution of genetic recombination and the buildup of mutational load in populations. We compiled a list of 758 yeast gene deletions causing growth defects (from the Munich Information Center for Protein Sequences database and ref. 7).

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.

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.