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The synthetic genetic interaction spectrum of essential genes

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Abstract

The nature of synthetic genetic interactions involving essential genes (those required for viability) has not been previously examined in a broad and unbiased manner. We crossed yeast strains carrying promoter-replacement alleles for more than half of all essential yeast genes1 to a panel of 30 different mutants with defects in diverse cellular processes. The resulting genetic network is biased toward interactions between functionally related genes, enabling identification of a previously uncharacterized essential gene (PGA1) required for specific functions of the endoplasmic reticulum. But there are also many interactions between genes with dissimilar functions, suggesting that individual essential genes are required for buffering many cellular processes. The most notable feature of the essential synthetic genetic network is that it has an interaction density five times that of nonessential synthetic genetic networks2,3, indicating that most yeast genetic interactions involve at least one essential gene.

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Acknowledgements

We thank G. Bader for assistance with the comparison of our genetic interactions to known genetic and protein-protein interactions; A. Tong for assistance in SGA query selection and experiments, critical evaluation of the manuscript and help with network visualization; H. Ding for assistance with data analysis; and O. Ryan, H. Lu, M. McCabe, O. Morozova and W. Siu for technical contributions. This work was funded by grants from Canadian Institutes of Health Research, Genome Canada and the Ontario Genomics Institute to T.R.H., C.B., B.J.A. and G.W.B. A.P.D. was funded by a C.H. Best Postdoctoral Fellowship and J.H. was funded by an Estate of Betty Irene West/Canadian Institutes of Health Research doctoral research award.

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Competing interests

The authors declare no competing financial interests.

Correspondence to Timothy R Hughes.

Supplementary information

  1. Supplementary Table 1

    Query strains used in this study. (PDF 56 kb)

  2. Supplementary Methods (PDF 97 kb)

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Figure 1: Matrix display of SGA data.
Figure 2: Allele specificity of essential gene interactions.
Figure 3: Network diagram summarizing 229 synthetic genetic interactions between nine different queries (sec1-1ts, sec7-1ts, sec15-1ts, sec18-1ts, exo84-102ts, rfc5-1ts, lrp1-Δ, rps17a-Δ and slt2-Δ) and 147 strains in the TetO7-promoter array.
Figure 4: Analysis of DNA replication in the rfc5-1 mutants.
Figure 5: PGA1 (also known as YNL158W) is required for normal protein processing of ALP and Gas1p.
Figure 6: Characteristics of the essential SGA network.