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学科主题: 医学信息学
题名:
Protein evolution on a human signaling network
作者: Cui, Qinghua1,3; Purisima, Enrico O.1; Wang, Edwin1,2
刊名: BMC SYSTEMS BIOLOGY
发表日期: 2009-02-18
DOI: 10.1186/1752-0509-3-21
卷: 3
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Mathematical & Computational Biology
研究领域[WOS]: Mathematical & Computational Biology
关键词[WOS]: PROGRAMMED CELL-DEATH ; REGULATORY NETWORK ; CYTOCHROME-C ; MOTIFS ; PATHWAYS ; GENES ; APOPTOSIS ; DYNAMICS
英文摘要:

Background: The architectural structure of cellular networks provides a framework for innovations as well as constraints for protein evolution. This issue has previously been studied extensively by analyzing protein interaction networks. However, it is unclear how signaling networks influence and constrain protein evolution and conversely, how protein evolution modifies and shapes the functional consequences of signaling networks. In this study, we constructed a human signaling network containing more than 1,600 nodes and 5,000 links through manual curation of signaling pathways, and analyzed the d(N)/d(S) values of human-mouse orthologues on the network.

Results: We revealed that the protein d(N)/d(S) value decreases along the signal information flow from the extracellular space to nucleus. In the network, neighbor proteins tend to have similar d(N)/d(S) ratios, indicating neighbor proteins have similar evolutionary rates: co-fast or co-slow. However, different types of relationships (activating, inhibitory and neutral) between proteins have different effects on protein evolutionary rates, i.e., physically interacting protein pairs have the closest evolutionary rates. Furthermore, for directed shortest paths, the more distant two proteins are, the less chance they share similar evolutionary rates. However, such behavior was not observed for neutral shortest paths. Fast evolving signaling proteins have two modes of evolution: immunological proteins evolve more independently, while apoptotic proteins tend to form network components with other signaling proteins and share more similar evolutionary rates, possibly enhancing rapid information exchange between apoptotic and other signaling pathways.

Conclusion: Major network constraints on protein evolution in protein interaction networks previously described have been found for signaling networks. We further uncovered how network characteristics affect the evolutionary and co-evolutionary behavior of proteins and how protein evolution can modify the existing functionalities of signaling networks. These new insights provide some general principles for understanding protein evolution in the context of signaling networks.

语种: 英语
项目资助者: Genomics and Health Initiative
WOS记录号: WOS:000264392800002
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/62080
Appears in Collections:基础医学院_医学信息学系_期刊论文

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作者单位: 1.Natl Res Council Canada, Biotechnol Res Inst, Montreal, PQ H4P 2R2, Canada
2.McGill Univ, Ctr Bioinformat, Montreal, PQ, Canada
3.Peking Univ, Hlth Sci Ctr, Dept Med Informat, Beijing 100871, Peoples R China

Recommended Citation:
Cui, Qinghua,Purisima, Enrico O.,Wang, Edwin. Protein evolution on a human signaling network[J]. BMC SYSTEMS BIOLOGY,2009,3.
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