The impact of the genetic background on gene deletion phenotypes in Saccharomyces cerevisiae

• Published in: Molecular systems biology Vol. 15; no. 12; pp. e8831 - n/a
• Main Authors: Galardini, Marco, Busby, Bede P, Vieitez, Cristina, Dunham, Alistair S, Typas, Athanasios, Beltrao, Pedro
• Format: Journal Article
• Language: English
• Published: Germany EMBO Press 01.12.2019; John Wiley and Sons Inc; Springer Nature
• Subjects: chemical genomics; Gene Deletion; Gene expression; Gene Knockout Techniques; Genes; genetic background; Genome-wide association studies; Genomes; Genotype; Growth models; Laboratories; LoF phenotypes; Loss of Function Mutation; Mutation; Phenotype; Phenotypes; Pleiotropy; Saccharomyces cerevisiae; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - growth & development; Saccharomyces cerevisiae Proteins - genetics; Yeast; Yeasts; LoF phenotypes; Saccharomyces cerevisiae; genetic background; chemical genomics
• ISSN: 1744-4292; 1744-4292
• DOI: 10.15252/msb.20198831

Loss‐of‐function (LoF) mutations associated with disease do not manifest equally in different individuals. The impact of the genetic background on the consequences of LoF mutations remains poorly characterized. Here, we systematically assessed the changes in gene deletion phenotypes for 3,786 gene knockouts in four Saccharomyces cerevisiae strains and 38 conditions. We observed 18.5% of deletion phenotypes changing between pairs of strains on average with a small fraction conserved in all four strains. Conditions causing higher wild‐type growth differences and the deletion of pleiotropic genes showed above‐average changes in phenotypes. In addition, we performed a genome‐wide association study (GWAS) for growth under the same conditions for a panel of 925 yeast isolates. Gene–condition associations derived from GWAS were not enriched for genes with deletion phenotypes under the same conditions. However, cases where the results were congruent indicate the most likely mechanism underlying the GWAS signal. Overall, these results show a high degree of genetic background dependencies for LoF phenotypes. Synopsis A systematic evaluation of conditional gene essentiality changes across four Saccharomyces cerevisiae strains shows that on average, 18.5% of gene deletion phenotypes change between any pair of strains, indicating widespread genetic background effects. Gene deletion growth measurements are performed for 38 conditions in four S. cerevisiae genetic backgrounds. On average 18.5% of LoF phenotypes change between pairs of strains. Conditions with highest stress differences between strains and pleiotropic genes explain some of the differences. A systematic evaluation of conditional gene essentiality changes across four Saccharomyces cerevisiae strains shows that on average, 18.5% of gene deletion phenotypes change between any pair of strains, indicating widespread genetic background effects.