Schematic representation of the selective constraint levels expected along two hypothetical signaling pathways with different connection patterns. (A) Pathway receiving multiple signaling inputs along the pathway and with a single output. In this scenario, selective constraint levels will be higher at the downstream part, since the elements are progressively involved in a greater number of pathways. (B) Pathway with multiple outputs along the pathway (i.e., with multiple branching points able to transmit information to other pathways). In this scenario, the selective constraint levels will be higher for the upstream elements. The more constrained elements (nodes) are darker. The numbers in the nodes represent the number of pathways in which each element is involved.
