Different sets of QTLs influence fitness variation in yeast

We have carried out a combination of in-lab-evolution (ILE) and congenic crosses to identify the gene sets that contribute to the ability of yeast cells to survive under alkali stress.Each selected line acquired a different set of mutations, all resulting in the same phenotype. We identified a total of 15 genes in ILE and 17 candidates in the congenic approach, and studied their individual contribution to the phenotype.The total additive effect of the QTLs was much larger than the difference between the ancestor and the evolved strains, suggesting epistatic interactions between the QTLs.None of the genes identified encode structural components of the pH machinery. Instead, most encode regulatory functions, such as ubiquitin ligases, chromatin remodelers, GPI anchoring and copper/iron sensing transcription factors

Environmental Stresses Disrupt Telomere Length Homeostasis

Telomeres protect the chromosome ends from degradation and play crucial roles in cellular aging and disease. Recent studies have additionally found a correlation between psychological stress, telomere length, and health outcome in humans. However, studies have not yet explored the causal relationship between stress and telomere length, or the molecular mechanisms underlying that relationship. Using yeast as a model organism, we show that stresses may have very different outcomes: alcohol and acetic acid elongate telomeres, whereas caffeine and high temperatures shorten telomeres. Additional treatments, such as oxidative stress, show no effect. By combining genome-wide expression measurements with a systematic genetic screen, we identify the Rap1/Rif1 pathway as the central mediator of the telomeric response to environmental signals. These results demonstrate that telomere length can be manipulated, and that a carefully regulated homeostasis may become markedly deregulated in opposing directions in response to different environmental cues

Kinetics of telomere length change after exposure to environmental stresses.

<p>Wild-type yeast strain BY4741 was grown in the presence of various stresses and then released. <b>A</b>. YEPD containing 5% ethanol (released to YEPD after 300 generations). <b>B</b>. YEPD+8 mM caffeine (released to YEPD after 90 generations). <b>C</b>. YEPD at 37°C (released back to 30°C after 100 generations).</p

Different stresses affect telomere length via different genes.

<p>The effect of ethanol, caffeine and high temperature on telomere length was tested on strains carrying individual gene deletions/hypomorphic mutations. Each mutant was grown under the relevant stress for 100 generations and its telomere length was measured using Southern blot analysis. <b>A–C</b>. The X-axis shows the initial length of each mutant and the Y-axis shows the elongation or shortening after 100 generations. Each strain analyzed is represented by a circle (wt in green). A strong correlation (demarked by a red line; ±5% SD) was seen between the initial length and the effect of the stress. <b>A</b>. Ethanol. <b>B</b>. Caffeine. <b>C</b>. 37°C. <b>D</b>. Each bar represents the ratio between the initial telomere length and the elongation after 100 generations in ethanol. Very short <i>tlm</i> mutants (below 200 nt long) could be clearly separated into two groups: mutants of the Tel1 pathway (<i>tel1Δ</i>, <i>mre11Δ</i>, <i>rad50Δ</i>, <i>xrs2Δ</i>) were highly responsive to ethanol stress, while mutants of the NMD (<i>nam7Δ</i>, <i>upf3Δ</i>, <i>nmd2Δ</i>) and Ku (<i>yku70Δ</i>, <i>yku80Δ</i>) pathways show little telomeric elongation under ethanol stress.</p