Serially-regulated biological networks fully realize a constrained set of functions

TL;DR

This paper demonstrates that biologically plausible serially-regulated networks are limited to direct functionality, but can realize all such functions, highlighting their inherent constraints and versatility.

Contribution

It proves that serial regulation enforces a direct functionality constraint and shows these networks can achieve all functions within this limitation under realistic conditions.

Findings

Networks are constrained to direct functionality despite feedback loops.

All networks can realize all functions permitted by the constraint.

Serial regulation networks are functionally versatile within their constraints.

Abstract

We show that biological networks with serial regulation (each node regulated by at most one other node) are constrained to {\it direct functionality}, in which the sign of the effect of an environmental input on a target species depends only on the direct path from the input to the target, even when there is a feedback loop allowing for multiple interaction pathways. Using a stochastic model for a set of small transcriptional regulatory networks that have been studied experimentally, we further find that all networks can achieve all functions permitted by this constraint under reasonable settings of biochemical parameters. This underscores the functional versatility of the networks.