Exposing the fitness contribution of duplicated genes

Duplicate genes from the whole-genome duplication (WGD) in yeast are often dispensable-removing one copy has little or no phenotypic consequence(1,2). It is unknown, however, whether such dispensability reflects insignificance of the ancestral function or compensation from paralogs(3-7). 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.