Figure 1

Mechanisms of network evolution. Continuous lines represent an interaction and dashed lines represent orthologous relationships. (a) A conserved interaction between two species requires both interaction partners to be conserved by having identifiable orthologs. (b) Two mechanisms of network rewiring can be defined: interaction rewiring and protein change. Interaction rewiring is the gain or loss of an interaction but retention of both binding partners. Using species 1 as the reference, the illustrated interaction rewiring event in species 2 is an interaction loss between A' and B', shown by the gray line. Swapping the reference species results in an interaction gain between A and B. Protein change is the gain or loss of at least one of the binding partners. Using species 1 as the reference, the illustrated protein change is a protein gain of C'. The lack of an ortholog in species 1 indicates that C' is specific to species 2. (c) Specificity swapping in the mitogen-activated protein kinase (MAPK) pathway in the comparison between Saccharomyces cerevisiae and higher eukaryote interaction networks (adapted from Mody et al. [36]). The yeast Pbs2 activates Hog1, and Slt2 activates Rlm1, while in humans (and other higher eukaryotes) these interactions rewire and MEK1/2 (the Pbs2 ortholog) activates extracellular signal-regulated kinase 1/2 (ERK1/2; ortholog of Fus3), and p38α (the Hog1 ortholog) activates myocyte-specific enhancer factor 2A (MEF2A; the Rlm1 ortholog). MAPKK, MAPK kinase; TF, transcription factor.