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Robustness against mutations in genetic networks of yeast

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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Figure 1: Sequence similarity versus fitness effect of null mutations in 45 duplicated yeast genes.
Figure 2: Similarity in expression pattern versus fitness effect of null mutations in 45 duplicated yeast genes.
Figure 3: Fitness effect distribution of loss-of-function mutations.
Figure 4: Similar distribution of fitness effects of block-duplicated genes and all other genes on chromosome V.
Figure 5: Genes with weak fitness effect do not have more related genes in the yeast genome than do genes with strong fitness effects.
Figure 6: Genes similar to those with weak fitness effects and to those with strong fitness effects do not show systematic differences in their similarities.

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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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Correspondence to Andreas Wagner.

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Wagner, A. Robustness against mutations in genetic networks of yeast. Nat Genet 24, 355–361 (2000). https://doi.org/10.1038/74174

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