  Protein interaction networks aim to summarize the complex interplay of
proteins in an organism. Early studies suggested that the position of a protein
in the network determines its evolutionary rate but there has been considerable
disagreement as to what extent other factors, such as protein abundance, modify
this reported dependence.
  We compare the genomes of Saccharomyces cerevisiae and Caenorhabditis elegans
with those of closely related species to elucidate the recent evolutionary
history of their respective protein interaction networks. Interaction and
expression data are studied in the light of a detailed phylogenetic analysis.
The underlying network structure is incorporated explicitly into the
statistical analysis.
  The increased phylogenetic resolution, paired with high-quality interaction
data, allows us to resolve the way in which protein interaction network
structure and abundance of proteins affect the evolutionary rate. We find that
expression levels are better predictors of the evolutionary rate than a
protein's connectivity. Detailed analysis of the two organisms also shows that
the evolutionary rates of interacting proteins are not sufficiently similar to
be mutually predictive.
  It appears that meaningful inferences about the evolution of protein
interaction networks require comparative analysis of reasonably closely related
species. The signature of protein evolution is shaped by a protein's abundance
in the organism and its function and the biological process it is involved in.
Its position in the interaction networks and its connectivity may modulate this
but they appear to have only minor influence on a protein's evolutionary rate.

Molecular Networks;Disordered Systems and Neural Networks;Populations and Evolution