1 Modular Co-evolution of metabolic networks Zhao Jing.
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Transcript of 1 Modular Co-evolution of metabolic networks Zhao Jing.
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Background
Results/Discussion
•Topological modules and their functions
•The similarity between the phylogenetic profiles of enzymes within modules
•Determining the evolutionary ages of modules
•Evolutionary rates of enzyme genes in modules
•Comparison the Humo sapien network with its random counterparts
Conclusion
Outline
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Background
Life’s complex Pyramid
Oltvai, Z.N., Barabási, A.-L., Life’s Complexity Pyramid, SCIENCE, 2002, 298:763-764.
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Functional modules: protein complexes, signalling/metabolic pathways and transcriptional clusters
Evolutionary modules: cohesive evolutionary blocks in cellular systems
Network topological modules
Different aspects of modules:
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Functional modules => evolutionary modules
Snel B, Huynen MA: Quantifying Modularity in the Evolution of Biomolecular Systems. Genome Res 2004 14:391-397.
Work 1
1387 functional modules in total
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Campillos M, von Mering C, Jensen LJ, Bork P: Identification and analysis of evolutionarily cohesive functional modules in protein networks. Genome Research 2006, 16:374-382.
Evolutionary age
Work 2
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Evolutionary rate
CheChen Y, Dokholyan NV: The coordinated evolution of yeast proteins is constrained by functional modularity Trends in Genetics 2006, 22(8):416-419
Work 3
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Evolutionary modules => functional modules
von Mering C, Zdobnov EM, Tsoka S, Ciccare FD, Pereira-Leal JB, Ouzounis CA, Bork P: Genome evolution reveals biochemical networks and functional modules. PNAS
2003, 100:15428-15433.
Network: E.coli PPI network predicted by STRING ; each node is a COG
Modules: topological modules got by network clustering Reference functional modules: 144 e.coli metabolic pathways from EcoCyc
Result: 74% of the known metabolic enzymes clustering together in modules
Work 1
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Yamada T, Kanehisa M, Goto S: Extraction of phylogenetic network modules from the metabolic network. BMC Bioinformatics 2006, 7(1):130.
Yamada T, Goto S, Kanehisa M: Extraction of Phylogenetic Network Modules from Prokayrote Metabolic Pathways. Genome Informatics 2004, 15:249-258
Network: enzyme graph including all the organisms in KEGG
Work 2
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Topological modules = > functional modules
Guimera R, Nunes Amaral LA: Functional cartography of complex metabolic networks. Nature 2005, 433(7028):895-900.
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Zhao J, Yu H, Luo J, Cao Z, Li Y: Hierarchical modularity of nested bow-ties in metabolic networks. BMC Bioinformatics 2006:7:386.
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Fraser H, Hirsh A, Steinmetz L, Scharfe C, Feldman M: Evolutionary Rate in the Protein Interaction Network. Science 2002, 296:750-752.
Work 1
How network topology affect protein evolution?
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Work 2
Vitkup D, Kharchenko P, Wagner A: Influence of metabolic network structure and function on enzyme evolution. Genome Biology 2006, 7(5):R39.
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Work 3
Light S, Kraulis P, Elofsson A: Preferential attachment in the evolution of metabolic networks. BMC Bioinformatics 2005, 6:159.
The average connectivity for enzymes in phylogenetic groups 1–5
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Work 4
Fraser H: Modularity and evolutionary constraint on proteins. Nature Genetics 2005, 37(4):351-352.
Protein interaction hubs situated within modules are more evolutionarily constrained(have lower mean evolutionary rate)than those bridging different modules.
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Identifying topological modules and their functions
Core-periphery organization of modules Table 1
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Totally 12 of the 25 modules (module 7,3,25,9,16,4,6,22,12,15,19,21) were found to be evolutionary modules, most of which are periphery modules.
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The evolutionary ages of modules
We classified enzymes in the Homo sapiens network into seven evolutionary ages: (1) Prokaryota; (2) Protists; (3) Fungi;( 4) Nematodes;(5) Arthropods;(6)
Mammalian and (7) Human
Table 2
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Evolutionary rates of enzyme genes in modules
Spearman’s rank correlation is r= -0.4983, P-value= 0.011.
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Comparison the Humo sapien network with its random counterparts
(1) topological null model
Z-score=19
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Conclusions
From Topology: metabolic networks exhibit highly modular core-periphery organization pattern.
From Function: The core modules perform housekeeping functions, the periphery modules accomplish relatively specific functions.
From Evolution: The core modules are more evolutionarily conserved, the periphery modules appear later in evolution history.
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The core-periphery modularity organization reflects the functional and evolutionary requirement of metabolic system.