title: Dosage sensitivity and the evolution of gene families in yeast.
abstract: According to what we term the balance hypothesis, an imbalance in the concentration of the subcomponents of a protein-protein complex can be deleterious. If so, there are two consequences: first, both underexpression and overexpression of protein complex subunits should lower fitness, and second, the accuracy of transcriptional co-regulation of subunits should reflect the deleterious consequences of imbalance. Here we show that all these predictions are upheld in yeast (Saccharomyces cerevisiae). This supports the hypothesis that dominance is a by-product of physiology and metabolism rather than the result of selection to mask the deleterious effects of mutations. Beyond this, single-gene duplication of protein subunits is expected to be harmful, as this, too, leads to imbalance. As then expected, we find that members of large gene families are rarely involved in complexes. The balance hypothesis therefore provides a single theoretical framework for understanding components both of dominance and of gene family size.
authors.affiliation: Department of Biology and Biochemistry, University of Bath, Bath, Somerset BA2 7AY, UK.
authors.forename: Balázs
authors.initials: B
authors.lastname: Papp
authors.forename: Csaba
authors.initials: C
authors.lastname: Pál
authors.forename: Laurence D
authors.initials: LD
authors.lastname: Hurst
mesh_terms: D019143:Evolution, Molecular; D018628:Gene Dosage; D005800:Genes, Fungal; D006579:Heterozygote; D046911:Macromolecular Substances; D008957:Models, Genetic; D005810:Multigene Family; D016296:Mutagenesis; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics
chemical_list: D046911:Macromolecular Substances; D029701:Saccharomyces cerevisiae Proteins