1999 | H. Jeong, S. P. Mason, A.-L. Barabási and Z. N. Oltvai
The chapter discusses the role of proteins in cellular networks and how their connectivity affects their phenotypic consequences. It highlights the shift from traditional cell biology, which focuses on individual protein functions, to a post-genomic view that emphasizes protein-protein interactions and contextual roles within functional modules. The study uses the yeast *S. cerevisiae* as a model to demonstrate that the lethality of a single gene deletion is highly influenced by the topological position of its protein product in the complex network of molecular interactions.
The protein-protein interaction network of *S. cerevisiae* consists of 1870 proteins and 2240 direct physical interactions. The network is characterized by a scale-free topology, where a few highly connected proteins play a central role, mediating interactions among numerous less connected proteins. This structure allows the network to tolerate random mutations but is fragile when the most connected nodes are removed.
The authors find that the likelihood of a protein being essential (lethal when deleted) correlates strongly with its connectivity. Highly connected proteins, which are central to the network, are three times more likely to be essential compared to proteins with fewer interactions. This suggests that the robustness of the network against mutations is not only due to individual biochemical functions and genetic redundancy but also to the organization of interactions and the topological position of proteins within the network.
The findings indicate that the inhomogeneous structure observed in both metabolic and protein interaction networks is a result of evolutionary selection, and that future studies in other organisms are likely to uncover similar network topologies. This emphasizes the importance of integrated approaches that consider both individual and contextual properties of cellular networks to better understand cell dynamics and robustness.The chapter discusses the role of proteins in cellular networks and how their connectivity affects their phenotypic consequences. It highlights the shift from traditional cell biology, which focuses on individual protein functions, to a post-genomic view that emphasizes protein-protein interactions and contextual roles within functional modules. The study uses the yeast *S. cerevisiae* as a model to demonstrate that the lethality of a single gene deletion is highly influenced by the topological position of its protein product in the complex network of molecular interactions.
The protein-protein interaction network of *S. cerevisiae* consists of 1870 proteins and 2240 direct physical interactions. The network is characterized by a scale-free topology, where a few highly connected proteins play a central role, mediating interactions among numerous less connected proteins. This structure allows the network to tolerate random mutations but is fragile when the most connected nodes are removed.
The authors find that the likelihood of a protein being essential (lethal when deleted) correlates strongly with its connectivity. Highly connected proteins, which are central to the network, are three times more likely to be essential compared to proteins with fewer interactions. This suggests that the robustness of the network against mutations is not only due to individual biochemical functions and genetic redundancy but also to the organization of interactions and the topological position of proteins within the network.
The findings indicate that the inhomogeneous structure observed in both metabolic and protein interaction networks is a result of evolutionary selection, and that future studies in other organisms are likely to uncover similar network topologies. This emphasizes the importance of integrated approaches that consider both individual and contextual properties of cellular networks to better understand cell dynamics and robustness.