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Role of duplicate genes in genetic robustness against null mutations

Nature volume 421, pages 63–66 (2003)Cite this article

Abstract

Deleting a gene in an organism often has little phenotypic effect1,2,3,4,5, owing to two mechanisms of compensation4,5,6,7,8,9,10. The first is the existence of duplicate genes: that is, the loss of function in one copy can be compensated by the other copy or copies. The second mechanism of compensation stems from alternative metabolic pathways, regulatory networks, and so on. The relative importance of the two mechanisms has not been investigated except for a limited study, which suggested that the role of duplicate genes in compensation is negligible10. The availability of fitness data for a nearly complete set of single-gene-deletion mutants of the Saccharomyces cerevisiae genome11 has enabled us to carry out a genome-wide evaluation of the role of duplicate genes in genetic robustness against null mutations. Here we show that there is a significantly higher probability of functional compensation for a duplicate gene than for a singleton, a high correlation between the frequency of compensation and the sequence similarity of two duplicates, and a higher probability of a severe fitness effect when the duplicate copy that is more highly expressed is deleted. We estimate that in S. cerevisiae at least a quarter of those gene deletions that have no phenotype are compensated by duplicate genes.

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Figure 1: Distributions of fitness (f).
Figure 2: Distribution of mean fitness differences between randomly selected gene pairs (100,000 replicates each with 418 gene pairs) under the YPD growth condition.
Figure 3: Relationship between protein distance and fitness effect of deletion.

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Acknowledgements

We thank M. Long, T. Oakley, D. Nicolae, K. Thornton, A. Deutschbauer and J. Zhang for discussions and comments. This work was supported by NIH grants to W.H.L and to R.W.D.

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  1. Zhenglong Gu and Lars M. Steinmetz: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Ecology & Evolution, University of Chicago, 1101 East 57th Street, Chicago, Illinois, 60637, USA

    Zhenglong Gu & Wen-Hsiung Li

  2. Department of Biochemistry, and Stanford Genome Technology Center, Stanford University School of Medicine, Stanford, California, 94305, USA

    Lars M. Steinmetz, Curt Scharfe & Ronald W. Davis

  3. Departments of Zoology and Genetics, Iowa State University, Ames, Iowa, 50011, USA

    Xun Gu

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  1. Zhenglong Gu
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Correspondence to Wen-Hsiung Li.

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Gu, Z., Steinmetz, L., Gu, X. et al. Role of duplicate genes in genetic robustness against null mutations. Nature 421, 63–66 (2003). https://doi.org/10.1038/nature01198

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