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Robustness against mutations in genetic networks of yeast

Nature Genetics volume 24, pages 355361 (2000) | Download Citation

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Abstract

There are two principal mechanisms that are responsible for the ability of an organism's physiological and developmental processes to compensate for mutations. In the first, genes have overlapping functions, and loss-of-function mutations in one gene will have little phenotypic effect if there are one or more additional genes with similar functions. The second mechanism has its origin in interactions between genes with unrelated functions, and has been documented in metabolic and regulatory gene networks. Here I analyse, on a genome-wide scale, which of these mechanisms of robustness against mutations is more prevalent. I used functional genomics data from the yeast Saccharomyces cerevisiae to test hypotheses related to the following: if gene duplications are mostly responsible for robustness, then a correlation is expected between the similarity of two duplicated genes and the effect of mutations in one of these genes. My results demonstrate that interactions among unrelated genes are the major cause of robustness against mutations. This type of robustness is probably an evolved response of genetic networks to stabilizing selection.

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Acknowledgements

I thank E. Charnov, W. Fontana, P. d'Haeseleer, R. Miller, M. Lynch, D. Natvig and M. Werner-Washburne for discussions on the subject. Th financial and computational support of the Santa Fe Institute and of the Albuquerque High Performance Computing Center is gratefully acknowledged.

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Affiliations

  1. Department of Biology, University of New Mexico, and The Santa Fe Institute, Albuquerque, New Mexico, USA.

    • Andreas Wagner

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Correspondence to Andreas Wagner.

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DOI

https://doi.org/10.1038/74174

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