Abstract:

The protein-protein interaction (PPI) network offers a conceptual framework for better understanding the functional organization of the proteome. However, the intricacy of network complexity complicates comprehensive analysis. Here, we adopted a phylogenic grouping method combined with force-directed graph simulation to decompose the human PPI network in a multi-dimensional manner. This network model enabled us to associate the network topological properties with evolutionary and biological implications. First, we found that ancient proteins occupy the core of the network, whereas young proteins tend to reside on the periphery. Second, the presence of age homophily suggests a possible selection pressure may have acted on the duplication and divergence process during the PPI network evolution. Lastly, functional analysis revealed that each age group possesses high specificity of enriched biological processes and pathway engagements, which could correspond to their evolutionary roles in eukaryotic cells. More interestingly, the network landscape closely coincides with the subcellular localization of proteins. Together, these findings suggest the potential of using conceptual frameworks to mimic the true functional organization in a living cell.

Notes:

Chen et al. (2014) adapted a phylogenic grouping method in conjunction with force-directed graph simulation to dissect the human interactome that enabled them to associate network properties with evolutionary and biological properties.

— Karagoz et al, Journal of Theoretical Biology (2016)

In humans, the human PPIN was decomposed according to the phylogenetic age groups of proteins (Chen et al. 2014) ... One important conclusion from these results is that the older, more central proteins tend to not develop new interactions over time... This avoidance of perturbation of aged proteins implies an overall network structure that may beconserved over time ... Understanding how networks evolve is important in characterizing cellular organization and evidence suggests that organizational schemes may be conserved among species.

— McCormack et al, Curr Plant Biol (2015)