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

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 unde...

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Autores principales: Boucher, Benjamin, Lee, Anna Y., Hallett, Michael, Jenna, Sarah
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4752231/
https://www.ncbi.nlm.nih.gov/pubmed/26871911
http://dx.doi.org/10.1371/journal.pcbi.1004738
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author Boucher, Benjamin
Lee, Anna Y.
Hallett, Michael
Jenna, Sarah
author_facet Boucher, Benjamin
Lee, Anna Y.
Hallett, Michael
Jenna, Sarah
author_sort Boucher, Benjamin
collection PubMed
description 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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spelling pubmed-47522312016-02-26 Structural and Functional Characterization of a Caenorhabditis elegans Genetic Interaction Network within Pathways Boucher, Benjamin Lee, Anna Y. Hallett, Michael Jenna, Sarah PLoS Comput Biol Research Article 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. Public Library of Science 2016-02-12 /pmc/articles/PMC4752231/ /pubmed/26871911 http://dx.doi.org/10.1371/journal.pcbi.1004738 Text en © 2016 Boucher et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Boucher, Benjamin
Lee, Anna Y.
Hallett, Michael
Jenna, Sarah
Structural and Functional Characterization of a Caenorhabditis elegans Genetic Interaction Network within Pathways
title Structural and Functional Characterization of a Caenorhabditis elegans Genetic Interaction Network within Pathways
title_full Structural and Functional Characterization of a Caenorhabditis elegans Genetic Interaction Network within Pathways
title_fullStr Structural and Functional Characterization of a Caenorhabditis elegans Genetic Interaction Network within Pathways
title_full_unstemmed Structural and Functional Characterization of a Caenorhabditis elegans Genetic Interaction Network within Pathways
title_short Structural and Functional Characterization of a Caenorhabditis elegans Genetic Interaction Network within Pathways
title_sort structural and functional characterization of a caenorhabditis elegans genetic interaction network within pathways
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4752231/
https://www.ncbi.nlm.nih.gov/pubmed/26871911
http://dx.doi.org/10.1371/journal.pcbi.1004738
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