title: Dominance from the perspective of gene-gene and gene-chemical interactions.
abstract: In this study, we used genetic interaction (GI) and gene-chemical interaction (GCI) data to compare mutations with different dominance phenotypes. Our analysis focused primarily on Saccharomyces cerevisiae, where haploinsufficient genes (HI; genes with dominant loss-of-function mutations) were found to be participating in gene expression processes, namely, the translation and regulation of gene transcription. Non-ribosomal HI genes (mainly regulators of gene transcription) were found to have more GIs and GCIs than haplosufficient (HS) genes. Several properties seem to lead to the enrichment of interactions, most notably, the following: importance, pleiotropy, gene expression level and gene expression variation. Importantly, after these properties were appropriately considered in the analysis, the correlation between dominance and GI/GCI degrees was still observed. Strikingly, for the GCIs of heterozygous strains, haploinsufficiency was the only property significantly correlated with the number of GCIs. We found ribosomal HI genes to be depleted in GIs/GCIs. This finding can be explained by their high variation in gene expression under different genetic backgrounds and environmental conditions. We observed the same distributions of GIs among non-ribosomal HI, ribosomal HI and HS genes in three other species: Schizosaccharomyces pombe, Drosophila melanogaster and Homo sapiens. One potentially interesting exception was the lack of significant differences in the degree of GIs between non-ribosomal HI and HS genes in Schizosaccharomyces pombe.
authors.affiliation: Bioinformatics Department, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, ul. Pawinskiego 5a, 02-106, Warsaw, Poland.
authors.forename: Arkadiusz
authors.initials: A
authors.lastname: Gladki
authors.affiliation: Bioinformatics Department, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, ul. Pawinskiego 5a, 02-106, Warsaw, Poland. piotr@ibb.waw.pl.|Plant Molecular Biology Department, University of Warsaw, Warsaw, Poland. piotr@ibb.waw.pl.
authors.forename: Piotr
authors.initials: P
authors.lastname: Zielenkiewicz
authors.affiliation: Bioinformatics Department, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, ul. Pawinskiego 5a, 02-106, Warsaw, Poland.
authors.forename: Szymon
authors.initials: S
authors.lastname: Kaczanowski
mesh_terms: D000818:Animals; D004331:Drosophila melanogaster / Q000235:genetics; D004843:Epistasis, Genetic; D059647:Gene-Environment Interaction; D005799:Genes, Dominant; D005808:Genes, Recessive; D057895:Haploinsufficiency; D006801:Humans; D009154:Mutation; D010641:Phenotype; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D012568:Schizosaccharomyces / Q000235:genetics
keywords: Genetic dominance; Genetic interactions; Gene–chemical interactions; Haploinsufficiency; Saccharomyces cerevisiae