Commensurate distances and similar motifs in genetic congruence and protein interaction networks in yeast

Ping Ye¹^,2 , Brian D Peyser³^,4 , Forrest A Spencer³^,4 and Joel S Bader¹^,2

¹The Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, MD 21218, USA

²The High-Throughput Biology Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA

³The McKusick-Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA

⁴The Department of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA

author email corresponding author email

BMC Bioinformatics 2005, 6:270doi:10.1186/1471-2105-6-270


Published:	9 November 2005

Abstract

Background

In a genetic interaction, the phenotype of a double mutant differs from the combined phenotypes of the underlying single mutants. When the single mutants have no growth defect, but the double mutant is lethal or exhibits slow growth, the interaction is termed synthetic lethality or synthetic fitness. These genetic interactions reveal gene redundancy and compensating pathways. Recently available large-scale data sets of genetic interactions and protein interactions in Saccharomyces cerevisiae provide a unique opportunity to elucidate the topological structure of biological pathways and how genes function in these pathways.

Results

We have defined congruent genes as pairs of genes with similar sets of genetic interaction partners and constructed a genetic congruence network by linking congruent genes. By comparing path lengths in three types of networks (genetic interaction, genetic congruence, and protein interaction), we discovered that high genetic congruence not only exhibits correlation with direct protein interaction linkage but also exhibits commensurate distance with the protein interaction network. However, consistent distances were not observed between genetic and protein interaction networks. We also demonstrated that congruence and protein networks are enriched with motifs that indicate network transitivity, while the genetic network has both transitive (triangle) and intransitive (square) types of motifs. These results suggest that robustness of yeast cells to gene deletions is due in part to two complementary pathways (square motif) or three complementary pathways, any two of which are required for viability (triangle motif).

Conclusion

Genetic congruence is superior to genetic interaction in prediction of protein interactions and function associations. Genetically interacting pairs usually belong to parallel compensatory pathways, which can generate transitive motifs (any two of three pathways needed) or intransitive motifs (either of two pathways needed).