title: Exposing the fitness contribution of duplicated genes.
abstract: Duplicate genes from the whole-genome duplication (WGD) in yeast are often dispensable--removing one copy has little or no phenotypic consequence. It is unknown, however, whether such dispensability reflects insignificance of the ancestral function or compensation from paralogs. Here, using precise competition-based measurements of the fitness cost of single and double deletions, we estimate the exposed fitness contribution of WGD duplicate genes in metabolism and bound the importance of their ancestral pre-duplication function. We find that the functional overlap between paralogs sufficiently explains the apparent dispensability of individual WGD genes. Furthermore, the lower bound on the fitness value of the ancestral function, which is estimated by the degree of synergistic epistasis, is at least as large as the average fitness cost of deleting single non-WGD genes. These results suggest that most metabolic functions encoded by WGD genes are important today and were also important at the time of duplication.
authors.affiliation: Department of Systems Biology, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: DeLuna
authors.forename: Kalin
authors.initials: K
authors.lastname: Vetsigian
authors.forename: Noam
authors.initials: N
authors.lastname: Shoresh
authors.forename: Matthew
authors.initials: M
authors.lastname: Hegreness
authors.forename: Maritrini
authors.initials: M
authors.lastname: Colón-González
authors.forename: Sharon
authors.initials: S
authors.lastname: Chao
authors.forename: Roy
authors.initials: R
authors.lastname: Kishony
mesh_terms: D000595:Amino Acid Sequence; D017124:Conserved Sequence; D004843:Epistasis, Genetic; D017353:Gene Deletion; D020440:Gene Duplication; D015966:Gene Expression Regulation, Fungal; D020131:Genes, Duplicate / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D029701:Saccharomyces cerevisiae Proteins