Mutations in a single signaling pathway allow growth on a different solvent than water

Since life is completely dependent on water, it is difficult to gauge the impact of solvent change. To analyze the role of water as a solvent in biology, we replaced water with heavy water (DO), and investigated the biological effects by a wide range of techniques, using the fission yeast as model organism. We show that high concentrations of DO lead to altered glucose metabolism, growth retardation, and inhibition of meiosis. However, mitosis and overall cell viability were only slightly affected. After prolonged incubation in DO, cells displayed gross morphological changes, thickened cell walls as well as aberrant septa and cytoskeletal organization. RNA sequencing revealed that DO causes a strong downregulation of most tRNAs and triggers activation of the general stress response pathway. Genetic screens identified several DO sensitive mutants, while mutants compromised in the cell integrity pathway, including the protein kinase genes , , and , that control cell wall biogenesis, were more tolerant to DO. We speculate that DO affects the phospholipid membrane or cell wall glycans causing an activation of the cell integrity pathway. In conclusion, the effects of solvent replacement are pleiotropic but the DO-triggered activation of the cell integrity pathway and subsequent increased deposition of cell wall material and septation problems appear most critical for the cell growth defects.