Structural and Functional Characterization of a Caenorhabditis elegans Genetic Interaction Network within Pathways.
PLoS Comput Biol
; 12(2): e1004738, 2016 Feb.
Article
em En
| MEDLINE
| ID: mdl-26871911
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.
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Base de dados:
MEDLINE
Assunto principal:
Caenorhabditis elegans
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Proteínas de Caenorhabditis elegans
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Redes Reguladoras de Genes
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Mapas de Interação de Proteínas
Limite:
Animals
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article