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Exposing the fitness contribution of duplicated genes

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Duplicate genes from the whole-genome duplication (WGD) in yeast are often dispensable—removing one copy has little or no phenotypic consequence1,2. It is unknown, however, whether such dispensability reflects insignificance of the ancestral function or compensation from paralogs3,4,5,6,7. 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.

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Figure 1: Measuring the extent of paralogous compensation.
Figure 2: Competition-based high-resolution fitness profiling of single and double deletions.
Figure 3: Dispensability of WGD genes is explained by paralogous compensation.
Figure 4: Exposed fitness of duplicated genes and bounds on fitness contribution of ancestral function.
Figure 5: Synergistic epistasis between WGD pairs correlates with conservation of amino acid sequence and protein interaction partners.
Figure 6: High occurrence of synergy between WGD gene pairs with at least one highly expressed member.

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  • 30 April 2008

    The HTML version of the manuscript originally contained several errors in the reference list. These errors have been corrected in the HTML version of the manuscript.


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We thank E. Angelino, N.Q. Balaban, N. Barkai, R. Chait, M. Elowitz, M. Ernebjerg, R. Kafri, E. Mancera, R. Milo, M. Vibranovski, D.R. Wagner, I. Wapinski, R. Ward and P. Yeh for helpful discussions and critical reading of the manuscript, M. Springer for help with flow cytometry, and C. Boone (University of Toronto) and J.S. Weissman (University of California San Francisco) for their gifts of strains and plasmids. This work was supported by a grant from the Human Frontiers Science Program to R.K.; A.D. is a Fellow of the Pew Program in the Biomedical Sciences.

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Correspondence to Roy Kishony.

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DeLuna, A., Vetsigian, K., Shoresh, N. et al. Exposing the fitness contribution of duplicated genes. Nat Genet 40, 676–681 (2008).

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