Abstract
BackgroundThe architecture of biological networks has been reported to exhibit high level of modularity, and to some extent, topological modules of networks overlap with known functional modules. However, how the modular topology of the molecular network affects the evolution of its member proteins remains unclear.ResultsIn this work, the functional and evolutionary modularity of Homo sapiens (H. sapiens) metabolic network were investigated from a topological point of view. Network decomposition shows that the metabolic network is organized in a highly modular core-periphery way, in which the core modules are tightly linked together and perform basic metabolism functions, whereas the periphery modules only interact with few modules and accomplish relatively independent and specialized functions. Moreover, over half of the modules exhibit co-evolutionary feature and belong to specific evolutionary ages. Peripheral modules tend to evolve more cohesively and faster than core modules do.ConclusionThe correlation between functional, evolutionary and topological modularity suggests that the evolutionary history and functional requirements of metabolic systems have been imprinted in the architecture of metabolic networks. Such systems level analysis could demonstrate how the evolution of genes may be placed in a genome-scale network context, giving a novel perspective on molecular evolution.
Highlights
The architecture of biological networks has been reported to exhibit high level of modularity, and to some extent, topological modules of networks overlap with known functional modules
We ask to which extent the identified topological modules of metabolic networks co-evolve. We explore this question by analysing the metabolic network of H. sapiens reconstructed from the KEGG database [41,42,43]
Comparison of the H. sapiens network with its randomised counterparts In order to investigate whether the topological, functional and evolutionary features of modularity we presented above are intrinsic for metabolic networks, we constructed two versions of randomised counterparts for the H. sapiens metabolic network and compared them with the real network
Summary
The architecture of biological networks has been reported to exhibit high level of modularity, and to some extent, topological modules of networks overlap with known functional modules. Cellular functions are carried out in a modular way, and functional modules are basic building blocks of cellular organization [1]. From the perspective of molecular biology, a functional module is regarded as a group of spatially isolated or chemically specific biological components that work together for a discrete biological function. Various functional modules such as protein complexes [2,3,4], signalling/metabolic pathways [5,6,7,8] and transcriptional clusters [9,10] have been detected from functional genomic techniques or bioinformatics analyses of genomic data. The metabolic network of H. sapiens consists of 1378 metabolites and 666 enzymes, with the biggest connected cluster includes 948 metabolites and 614 enzymes
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