Molecular Analysis of Adaptational Strategies under Heat Stress by Whole‐Genome Sequencing of Laboratory‐Evolved Saccharomyces cerevisiae

Abstract

Experimental evolution is an effective method to connect genotypes to phenotypes. The outcomes obtained from the method potentially facilitate the rational engineering of useful strains for bioproduction.In this study, we carried out experimental evolution of Saccharomyces cerevisiae under heat stress [1, 2]. In order to track the cell populations, intermediate strains obtained during the adaptational experiments have been preserved. Whole‐genome sequencing of 19 intermediate strains revealed that a total of 49 genetic mutations had emerged during the experimental evolution. A phylogenetic tree analysis showed that there were at least 5 events in which these strains had acquired mutations in a CDC25 gene. One of the CDC25 mutants successfully adapted to a 38°C‐environment. These mutations led to the downregulation of cAMP‐dependent protein kinase (PKA) signaling pathway, which controls variety of processes such as cell‐cycle progression and stress tolerance. In general, excessive downregulation of this pathway causes a trade‐off between induced thermotolerance and diminished growth rate. However, these strains have acquired thermotolerance without any growth defects. Our study demonstrates that experimental evolution leads to fine tuning of signaling pathways and engineering of beneficial cellular traits [3].Support or Funding InformationThis work was supported by a Grant‐in‐Aid for JSPS Fellows (No. 26‐1413) from Japan Society for the Promotion of Science, the commission for Development of Artificial Genes Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI), Japan, and, JST‐CREST.