To overcome the limitations mentioned in the previous paragraph, the analysis of co-expression data has been developed to supplement the direct comparison of individual gene expression changes [95] . In this procedure, a coexpression analysis of gene pairs within each species precedes the cross-comparison of the different organisms in the study. This approach thus primarily focuses on the similarity and differences of the orthologous genes within network, and is therefore ideally suited for the study of protein domain evolution and has already revealed that species-specific parts Fig. (3) . Evolutionary models for protein-protein interactions. The evolution of protein networks is tightly coupled to the addition or deletion of nodes. Additionally, events that introduce mutations in binding interfaces of proteins may result in the addition or loss of links in the network. Node addition may take place through e.g., domain duplication or horizontal gene transfer, while rewiring of the network is mediated by point mutations, alternative splice variants and changes in gene expression patterns.