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Genetic suppression interactions are highly conserved across genetically diverse yeast isolates
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Genetic suppression interactions are highly conserved across genetically diverse yeast isolates
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Journal Article
Genetic suppression interactions are highly conserved across genetically diverse yeast isolates
2025
Overview
Genetic suppression occurs when the phenotypic defects caused by a deleterious mutation are rescued by another mutation. Suppression interactions are of particular interest for genetic diseases, as they identify ways to reduce disease severity, thereby potentially highlighting avenues for therapeutic intervention. To what extent suppression interactions are influenced by the genetic background in which they operate remains largely unknown. However, a high degree of suppression conservation would be crucial for developing therapeutic strategies that target suppressors. To gain an understanding of the effect of the genetic context on suppression, we isolated spontaneous suppressor mutations of temperature-sensitive alleles of SEC17, TAO3, and GLN1 in 3 genetically diverse natural isolates of the budding yeast Saccharomyces cerevisiae. After identifying and validating the genomic variants responsible for suppression, we introduced the suppressors in all 3 genetic backgrounds, as well as in a laboratory strain, to assess their specificity. Ten out of 11 tested suppression interactions were conserved in the 4 yeast strains, although the extent to which a suppressor could rescue the temperature-sensitive mutant varied across genetic backgrounds. These results suggest that suppression mechanisms are highly conserved across genetic contexts, a finding that is potentially reassuring for the development of therapeutics that mimic genetic suppressors.Sometimes the detrimental effects of a mutation can be rescued by another mutation. For genetic diseases, such suppressor mutations may identify new therapeutic targets. However, it is unclear how genetic background influences suppression. To investigate this, Paltenghi and van Leeuwen studied yeast strains with different genetic makeups and identified mutations that rescued defective genes. The authors found that most suppression interactions were conserved across strains, though their effectiveness varied. This suggests that suppression mechanisms are broadly shared, which is promising for developing therapies that mimic genetic suppressors.
Publisher
Oxford University Press
Subject
