Structural and Functional Characterization of a Caenorhabditis elegans Genetic Interaction Network within Pathways

PLoS Comput Biol. 2016 Feb 12;12(2):e1004738. doi: 10.1371/journal.pcbi.1004738. eCollection 2016 Feb.

Abstract

A genetic interaction (GI) is defined when the mutation of one gene modifies the phenotypic expression associated with the mutation of a second gene. Genome-wide efforts to map GIs in yeast revealed structural and functional properties of a GI network. This provided insights into the mechanisms underlying the robustness of yeast to genetic and environmental insults, and also into the link existing between genotype and phenotype. While a significant conservation of GIs and GI network structure has been reported between distant yeast species, such a conservation is not clear between unicellular and multicellular organisms. Structural and functional characterization of a GI network in these latter organisms is consequently of high interest. In this study, we present an in-depth characterization of ~1.5K GIs in the nematode Caenorhabditis elegans. We identify and characterize six distinct classes of GIs by examining a wide-range of structural and functional properties of genes and network, including co-expression, phenotypical manifestations, relationship with protein-protein interaction dense subnetworks (PDS) and pathways, molecular and biological functions, gene essentiality and pleiotropy. Our study shows that GI classes link genes within pathways and display distinctive properties, specifically towards PDS. It suggests a model in which pathways are composed of PDS-centric and PDS-independent GIs coordinating molecular machines through two specific classes of GIs involving pleiotropic and non-pleiotropic connectors. Our study provides the first in-depth characterization of a GI network within pathways of a multicellular organism. It also suggests a model to understand better how GIs control system robustness and evolution.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans Proteins / genetics*
  • Caenorhabditis elegans Proteins / metabolism
  • Computational Biology
  • Gene Regulatory Networks / genetics*
  • Models, Biological
  • Protein Interaction Maps / genetics*

Substances

  • Caenorhabditis elegans Proteins

Grants and funding

This work was supported by grants from the Natural Sciences and Engineering Research Council (NSERC) of Canada and The Canada Foundation for Innovation. SJ is funded by the Canada Research Chair program. AYL is funded by the NSERC, and MH is founded by the NSERC and Genome Quebec. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.