Abstract

BackgroundLarge-scale evaluation of gene expression variation among Caenorhabditis elegans lines that have diverged from a common ancestor allows for the analysis of a novel class of biological networks – evolutionary gene coexpression networks. Comparative analysis of these evolutionary networks has the potential to uncover the effects of natural selection in shaping coexpression network topologies since C. elegans mutation accumulation (MA) lines evolve essentially free from the effects of natural selection, whereas natural isolate (NI) populations are subject to selective constraints.ResultsWe compared evolutionary gene coexpression networks for C. elegans MA lines versus NI populations to evaluate the role that natural selection plays in shaping the evolution of network topologies. MA and NI evolutionary gene coexpression networks were found to have very similar global topological properties as measured by a number of network topological parameters. Observed MA and NI networks show node degree distributions and average values for node degree, clustering coefficient, path length, eccentricity and betweeness that are statistically indistinguishable from one another yet highly distinct from randomly simulated networks. On the other hand, at the local level the MA and NI coexpression networks are highly divergent; pairs of genes coexpressed in the MA versus NI lines are almost entirely different as are the connectivity and clustering properties of individual genes.ConclusionIt appears that selective forces shape how local patterns of coexpression change over time but do not control the global topology of C. elegans evolutionary gene coexpression networks. These results have implications for the evolutionary significance of global network topologies, which are known to be conserved across disparate complex systems.

Highlights

  • Large-scale evaluation of gene expression variation among Caenorhabditis elegans lines that have diverged from a common ancestor allows for the analysis of a novel class of biological networks – evolutionary gene coexpression networks

  • This study clearly demonstrated a role for natural selection in constraining expression divergence, since a much higher fraction of mutation accumulation (MA) than natural isolate (NI) genes were found to be differentially expressed across populations

  • We evaluated the way that MA versus NI coexpressed gene pairs, along with the random gene pairs for each network, populate the C. elegans gene expression topological map by measuring Euclidean distances on the topological map between pairs of genes in the MA, NI or random networks

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Summary

Introduction

Large-scale evaluation of gene expression variation among Caenorhabditis elegans lines that have diverged from a common ancestor allows for the analysis of a novel class of biological networks – evolutionary gene coexpression networks. Determination of the effects of natural selection on network topologies was accomplished through the analysis of a novel class of gene coexpression networks that are distinct from the more familiar coexpression networks based on changes in expression over developmental time, tissue or experimental treatment. To build evolutionary gene coexpression networks, variation in levels of gene expression were measured across lines (populations) of Caenorhabditis elegans that have diverged from a common ancestor (Figure 1A). It was previously noted that C. elegans genes differentially expressed across lines are enriched for specific functional categories, chromosomal locations and gene coexpression mounts [9]

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