Abstract:
Gene regulatory networks (GRNs) consist of different
molecular interactions that closely work together to
establish proper gene expression in time and space.
Especially in higher eukaryotes, many questions remain
on how these interactions collectively coordinate
gene regulation. We study high quality GRNs
consisting of undirected protein–protein, genetic
and homologous interactions, and directed protein–
DNA, regulatory and miRNA–mRNA interactions in
the worm Caenorhabditis elegans and the plant Arabidopsis
thaliana. Our data-integration framework integrates
interactions in composite network motifs,
clusters these in biologically relevant, higher-order
topological network motif modules, overlays these
with gene expression profiles and discovers novel
connections between modules and regulators. Similarmodules
exist in the integrated GRNs of worm and
plant. We show how experimental or computational
methodologies underlying a certain data type impact
network topology. Through phylogenetic decomposition,
we found that proteins of worm and plant tend
to functionally interact with proteins of a similar age,
while at the regulatory level TFs favor same age, but
also older target genes. Despite some influence of
the duplication mode difference, we also observe at
the motif and module level for both species a preference
for age homogeneity for undirected and age
heterogeneity for directed interactions. This leads to a model where novel genes are added together to
the GRNs in a specific biological functional context,
regulated by one or more TFs that also target older
genes in the GRNs. Overall, we detected topological, functional and evolutionary properties of GRNs that
are potentially universal in all species.
