COMPACTNESS AND CYCLES IN SIGNAL TRANSDUCTION AND TRANSCRIPTIONAL REGULATION NETWORKS: A SIGNATURE OF NATURAL SELECTION?

We ask whether natural selection has shaped three biologically important features of 15 signal transduction networks and two genome-scale transcriptional regulation networks. These features are regulatory cycles, the lengths of the longest pathways through a network — a measure of network compactness — and the abundance of node pairs connected by many alternative regulatory pathways. We determine whether these features are significantly more or less abundant in biological networks than in randomized networks with the same distribution of incoming and outgoing connections per network node. We find that autoregulatory cycles are of exceptionally high abundance in transcriptional regulation networks. All other cycles, however, are significantly less abundant in several signal transduction networks. This suggests that the multistability caused by complex feedback loops in a network may interfere with the functioning of such networks. We also find that several of the networks we examine are more compact than expected by chance alone. This raises the possibility that the transmission of information through such networks, which is fastest in compact networks, is a biologically important characteristic of such networks.