Kavli Affiliate: V. S. Ramachandran
| Authors: Vignesh Ramachandran, Gregory Hatlestad and Travis White
| Summary:
Background: One way single-celled eukaryotes respond to DNA damage stress is by modifying their gene expression, facilitating genomic repair. Gene expression responses to DNA damage induced by methyl methanesulfonate (MMS) have been studied in the model organism Saccharomyces cerevisiae. However, lacking are investigations of the MMS stress responses in evolutionarily-related sensu stricto Saccharomyces species, including Saccharomyces cerevisiae. Methods: Next-generation Illumina RNA-sequencing was to characterize the entire transcriptomes of four evolutionarily-related species of yeast, S. cerevisiae, S. paradoxus, S. mikatae, and S. bayanus, under control and experimental (MMS) conditions. Subsequent genomic studies included gene set enrichment analysis, promoter analysis, and concentration gradient studies. Results: S. mikitae and S. paradoxus grew well in light of MMS while S. bayanus showed no growth. While there was fair overlap in induced and repressed genes, overall each species had unique expression responses. S. paradoxus and S. bayanus showed the most distinct changes with the former greatly inhibiting a large segment of its genome while the latter induced such segments. Gene set enrichment analysis revealed significantly modulated biologic, cellular, and molecular processes in each species. Promoter analysis revealed sets of induced/repressed transcription factors for genes highly modulated in the stress response. Concentration gradient studies of S. cerevisiae showed linear increase in gene expression of RAD54, DIN7, and IRC19 in response to increasing concentrations of MMS. Conclusion: Overall, we depict the transcriptome changes of four evolutionarily-related sensu stricto yeast species and several functional genomic analyses to provide a novel understanding of their responses to MMS.