title: Differential variation patterns between hubs and bottlenecks in human protein-protein interaction networks.
abstract: The identification, description and understanding of protein-protein networks are important in cell biology and medicine, especially for the study of system biology where the focus concerns the interaction of biomolecules. Hubs and bottlenecks refer to the important proteins of a protein interaction network. Until now, very little attention has been paid to differentiate these two protein groups.
  
  
  
  By integrating human protein-protein interaction networks and human genome-wide variations across populations, we described the differences between hubs and bottlenecks in this study. Our findings showed that similar to interspecies, hubs and bottlenecks changed significantly more slowly than non-hubs and non-bottlenecks. To distinguish hubs from bottlenecks, we extracted their special members: hub-non-bottlenecks and non-hub-bottlenecks. The differences between these two groups represent what is between hubs and bottlenecks. We found that the variation rate of hubs was significantly lower than that of bottlenecks. In addition, we verified that stronger constraint is exerted on hubs than on bottlenecks. We further observed fewer non-synonymous sites on the domains of hubs than on those of bottlenecks and different molecular functions between them.
  
  
  
  Based on these results, we conclude that in recent human history, different variation patterns exist in hubs and bottlenecks in protein interaction networks. By revealing the difference between hubs and bottlenecks, our results might provide further insights in the relationship between evolution and biological structure.
authors.affiliation: MOE Key Laboratory for Biodiversity Science and Ecological Engineering, College of Life Sciences, Beijing Normal University, No 19 Xinjiekouwai Street, Beijing, 100875, China. pangerli@bnu.edu.cn.|Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing, 100875, China. pangerli@bnu.edu.cn.
authors.forename: Erli
authors.initials: E
authors.lastname: Pang
authors.affiliation: MOE Key Laboratory for Biodiversity Science and Ecological Engineering, College of Life Sciences, Beijing Normal University, No 19 Xinjiekouwai Street, Beijing, 100875, China.|Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing, 100875, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Hao
authors.affiliation: MOE Key Laboratory for Biodiversity Science and Ecological Engineering, College of Life Sciences, Beijing Normal University, No 19 Xinjiekouwai Street, Beijing, 100875, China.|Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing, 100875, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.affiliation: MOE Key Laboratory for Biodiversity Science and Ecological Engineering, College of Life Sciences, Beijing Normal University, No 19 Xinjiekouwai Street, Beijing, 100875, China.|Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing, 100875, China.
authors.forename: Kui
authors.initials: K
authors.lastname: Lin
mesh_terms: D019143:Evolution, Molecular; D014644:Genetic Variation; D015894:Genome, Human; D006801:Humans; D000072417:Protein Domains; D025941:Protein Interaction Mapping; D060066:Protein Interaction Maps; D011506:Proteins / Q000737:chemistry* / Q000235:genetics
chemical_list: D011506:Proteins
keywords: Bottlenecks; Hubs; Protein interaction network; Variation rate