4 research outputs found
Neutral forces acting on intragenomic variability shape the Escherichia coli regulatory network topology
Cis-regulatory networks (CRNs) play a central role in cellular decision
making. Like every other biological system, CRNs undergo evolution,
which shapes their properties by a combination of adaptive
and nonadaptive evolutionary forces. Teasing apart these forces is
an important step toward functional analyses of the different components
of CRNs, designing regulatory perturbation experiments,
and constructing synthetic networks. Although tests of neutrality
and selection based on molecular sequence data exist, no such tests
are currently available based on CRNs. In this work, we present
a unique genotype model of CRNs that is grounded in a genomic
context and demonstrate its use in identifying portions of the
CRN with properties explainable by neutral evolutionary forces
at the system, subsystem, and operon levels.We leverage our model
against experimentally derived data from Escherichia coli. The
results of this analysis show statistically significant and substantial
neutral trends in properties previously identified as adaptive
in originラdegree distribution, clustering coefficient, and motifsラ
within the E. coli CRN. Our model captures the tightly coupled genomeヨ
interactome of an organism and enables analyses of how
evolutionary events acting at the genome level, such as mutation,
and at the population level, such as genetic drift, give rise to neutral
patterns that we can quantify in CRNs