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The balance of weak and strong interactions in genetic networks.

Poyatos JF - PLoS ONE (2011)

Bottom Line: Here, I found that weak interactions are important for the structure of genetic buffering between signaling pathways in Caenorhabditis elegans, and that the strength of the association between two genes correlates with the number of common interactors they exhibit.In yeast, I further showed a relation, although weak, between interaction strengths and some phenotypic/evolutionary features of the corresponding target genes.Overall, this work demonstrates a non-random organization of interaction strengths in genetic networks, a feature common to other complex networks, and that could reflect in this context how genetic variation is eventually influencing the phenotype.

View Article: PubMed Central - PubMed

Affiliation: Logic of Genomic Systems Laboratory, Spanish National Biotechnology Centre, Consejo Superior de Investigaciones Cientficas, Madrid, Spain. jpoyatos@cnb.csic.es

ABSTRACT
Genetic interactions are being quantitatively characterized in a comprehensive way in several model organisms. These data are then globally represented in terms of genetic networks. How are interaction strengths distributed in these networks? And what type of functional organization of the underlying genomic systems is revealed by such distribution patterns? Here, I found that weak interactions are important for the structure of genetic buffering between signaling pathways in Caenorhabditis elegans, and that the strength of the association between two genes correlates with the number of common interactors they exhibit. I also determined that this network includes genetic cascades balancing weak and strong links, and that its hubs act as particularly strong genetic modifiers; both patterns also identified in Saccharomyces cerevisae networks. In yeast, I further showed a relation, although weak, between interaction strengths and some phenotypic/evolutionary features of the corresponding target genes. Overall, this work demonstrates a non-random organization of interaction strengths in genetic networks, a feature common to other complex networks, and that could reflect in this context how genetic variation is eventually influencing the phenotype.

Show MeSH
Genetic interaction networks.A) Genetic interactions of different strengths between query and target genes constitutes the genetic network (red nodes represent query genes (); white/black nodes represent target genes interacting with one () or more than one () query. B) The C. elegans query network –constituted by the interactions between query genes only– represents the functional associations between different signaling pathways. IS is represented by the width of the edges, while the number of interactions with target genes other than queries (target-connectivity) is qualitatively described by node size. Those interactions of relatively weak strength that appeared most important to maintain the structure of functional linkages among pathways (network as a single-connected component, see main text) are highlighted in blue.
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pone-0014598-g001: Genetic interaction networks.A) Genetic interactions of different strengths between query and target genes constitutes the genetic network (red nodes represent query genes (); white/black nodes represent target genes interacting with one () or more than one () query. B) The C. elegans query network –constituted by the interactions between query genes only– represents the functional associations between different signaling pathways. IS is represented by the width of the edges, while the number of interactions with target genes other than queries (target-connectivity) is qualitatively described by node size. Those interactions of relatively weak strength that appeared most important to maintain the structure of functional linkages among pathways (network as a single-connected component, see main text) are highlighted in blue.

Mentions: The analysis of genetic interactions, and its systematic mapping to establish genetic networks, benefited enormously from the application of newly developed high-throughput experimental technologies. These tools are based on the possibility of generating collections of single gene mutants –both in unicellular [8], [9], [10], [11], [12] and multicellular [13], [14], [15] model organisms, and also in mammalian systems [16], [17] – that are then queried against a second large set of target gene mutations (Figure 1A and Box 1). Genetic interactions are thus defined for those cases in which the growth of the double mutant is different to its (expected) growth in the absence of any relationship (expected growth is usually quantified by the multiplicative effect of the single mutations (see [18], [19] and Materials and Methods).


The balance of weak and strong interactions in genetic networks.

Poyatos JF - PLoS ONE (2011)

Genetic interaction networks.A) Genetic interactions of different strengths between query and target genes constitutes the genetic network (red nodes represent query genes (); white/black nodes represent target genes interacting with one () or more than one () query. B) The C. elegans query network –constituted by the interactions between query genes only– represents the functional associations between different signaling pathways. IS is represented by the width of the edges, while the number of interactions with target genes other than queries (target-connectivity) is qualitatively described by node size. Those interactions of relatively weak strength that appeared most important to maintain the structure of functional linkages among pathways (network as a single-connected component, see main text) are highlighted in blue.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3037365&req=5

pone-0014598-g001: Genetic interaction networks.A) Genetic interactions of different strengths between query and target genes constitutes the genetic network (red nodes represent query genes (); white/black nodes represent target genes interacting with one () or more than one () query. B) The C. elegans query network –constituted by the interactions between query genes only– represents the functional associations between different signaling pathways. IS is represented by the width of the edges, while the number of interactions with target genes other than queries (target-connectivity) is qualitatively described by node size. Those interactions of relatively weak strength that appeared most important to maintain the structure of functional linkages among pathways (network as a single-connected component, see main text) are highlighted in blue.
Mentions: The analysis of genetic interactions, and its systematic mapping to establish genetic networks, benefited enormously from the application of newly developed high-throughput experimental technologies. These tools are based on the possibility of generating collections of single gene mutants –both in unicellular [8], [9], [10], [11], [12] and multicellular [13], [14], [15] model organisms, and also in mammalian systems [16], [17] – that are then queried against a second large set of target gene mutations (Figure 1A and Box 1). Genetic interactions are thus defined for those cases in which the growth of the double mutant is different to its (expected) growth in the absence of any relationship (expected growth is usually quantified by the multiplicative effect of the single mutations (see [18], [19] and Materials and Methods).

Bottom Line: Here, I found that weak interactions are important for the structure of genetic buffering between signaling pathways in Caenorhabditis elegans, and that the strength of the association between two genes correlates with the number of common interactors they exhibit.In yeast, I further showed a relation, although weak, between interaction strengths and some phenotypic/evolutionary features of the corresponding target genes.Overall, this work demonstrates a non-random organization of interaction strengths in genetic networks, a feature common to other complex networks, and that could reflect in this context how genetic variation is eventually influencing the phenotype.

View Article: PubMed Central - PubMed

Affiliation: Logic of Genomic Systems Laboratory, Spanish National Biotechnology Centre, Consejo Superior de Investigaciones Cientficas, Madrid, Spain. jpoyatos@cnb.csic.es

ABSTRACT
Genetic interactions are being quantitatively characterized in a comprehensive way in several model organisms. These data are then globally represented in terms of genetic networks. How are interaction strengths distributed in these networks? And what type of functional organization of the underlying genomic systems is revealed by such distribution patterns? Here, I found that weak interactions are important for the structure of genetic buffering between signaling pathways in Caenorhabditis elegans, and that the strength of the association between two genes correlates with the number of common interactors they exhibit. I also determined that this network includes genetic cascades balancing weak and strong links, and that its hubs act as particularly strong genetic modifiers; both patterns also identified in Saccharomyces cerevisae networks. In yeast, I further showed a relation, although weak, between interaction strengths and some phenotypic/evolutionary features of the corresponding target genes. Overall, this work demonstrates a non-random organization of interaction strengths in genetic networks, a feature common to other complex networks, and that could reflect in this context how genetic variation is eventually influencing the phenotype.

Show MeSH