Efficient microbial mutagenesis using heavy-ion beam (HIB) radiation is crucial for breeding. Here, Saccharomyces cerevisiae was irradiated with HIB across medium and high doses. Based on 65 randomly selected isolates, we systematically characterized the mutagenic features and preliminarily explored the influence of gene transcriptional activity on mutation susceptibility, while also modulating the intracellular state to optimize strain breeding. High-dose irradiation (120-210 Gy) resulted in a mutation frequency more than double that of the medium-dose (90 Gy), with minimal overlapping mutations between doses. Although mutation site numbers correlated with chromosome length broadly, they were not uniformly distributed at a finer scale. The overall expression of genes associated with mutation sites moderately exceeded the genome-wide background level (p < 0.05). By coupling radiation with osmotic stress, osmoregulatory-related genes were induced to express highly during irradiation. The proportion of osmotolerant mutants obtained from each coupled treatment group (averaging 27.62 %) was higher than that from the radiation-only group (11.43 %). Inference and validation indicated that early selection pressure alone could not fully account for this improvement, highlighting the importance of the intracellular state. Compared to radiation alone, coupled radiation-osmotic stress increased the distribution of mutations in osmotically inducible osmoregulatory-related genes. We propose that the enhanced transcriptional activity may alter local chromatin conformation, together with pre-activation of shared osmotic-radiation response genes, reshape the damage-repair-mutagenesis balance. The coupled treatment produced genetically stable, highly osmotolerant mutants with mutations synergistically regulating carbon metabolism, ion homeostasis, cell adhesion, and DNA replication. This work supports developing high-efficiency microbial breeding strategies.

• PMID: 41422992
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Journal Article

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Guo X, Xiao X, Dong X, Yin R, Zhang S, Zhang M, Luo G, Wang Y, Lu D

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