Significant conservation of synthetic lethal genetic interaction networks between distantly related eukaryotes

Scott J. Dixon, Yaroslav Fedyshyn, Judice L.Y. Koh, T. S.Keshava Prasad, Charly Chahwan, Gordon Chua, Kiana Toufighi, Anastasija Baryshnikova, Jacqueline Hayles, Kwang Lae Hoe, Dong Uk Kim, Han Oh Park, Chad L. Myers, Akhilesh Pandey, Daniel Durocher, Brenda J. Andrewsa, Charles Boone

Research output: Contribution to journalArticle

135 Scopus citations

Abstract

Synthetic lethal genetic interaction networks define genes that work together to control essential functions and have been studied extensively in Saccharomyces cerevisiae using the synthetic genetic array (SGA) analysis technique (ScSGA). The extent to which synthetic lethal or other genetic interaction networks are conserved between species remains uncertain. To address this question, we compared literature-curated and experimentally derived genetic interaction networks for two distantly related yeasts, Schizosaccharomyces pombe and S. cerevisiae. We find that 23% of interactions in a novel, high-quality S. pombe literature-curated network are conserved in the existing S. cerevisiae network. Next, we developed a method, called S. pombe SGA analysis (SpSGA), enabling rapid, high-throughput isolation of genetic interactions in this species. Direct comparison by SpSGA and ScSGA of ∼220 genes involved in DNA replication, the DNA damage response, chromatin remodeling, intracellular transport, and other processes revealed that ∼29% of genetic interactions are common to both species, with the remainder exhibiting unique, species-specific patterns of genetic connectivity. We define a conserved yeast network (CYN) composed of 106 genes and 144 interactions and suggest that this network may help understand the shared biology of diverse eukaryotic species.

Original languageEnglish (US)
Pages (from-to)16653-16658
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number43
DOIs
StatePublished - Oct 28 2008

Keywords

  • Comparative genomics
  • Saccharomyces cerevisiae
  • Schizosaccharomyces pombe
  • Synthetic genetic array

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Significant conservation of synthetic lethal genetic interaction networks between distantly related eukaryotes'. Together they form a unique fingerprint.

  • Cite this

    Dixon, S. J., Fedyshyn, Y., Koh, J. L. Y., Prasad, T. S. K., Chahwan, C., Chua, G., Toufighi, K., Baryshnikova, A., Hayles, J., Hoe, K. L., Kim, D. U., Park, H. O., Myers, C. L., Pandey, A., Durocher, D., Andrewsa, B. J., & Boone, C. (2008). Significant conservation of synthetic lethal genetic interaction networks between distantly related eukaryotes. Proceedings of the National Academy of Sciences of the United States of America, 105(43), 16653-16658. https://doi.org/10.1073/pnas.0806261105