Análise de diversas redes reguladoras em um contexto hierárquico mostra tendências consistentes para a colaboração em níveis médios

terça-feira, março 30, 2010

Analysis of diverse regulatory networks in a hierarchical context shows consistent tendencies for collaboration in the middle levels

Nitin Bhardwaj a, Koon-Kiu Yan a, and Mark B. Gerstein a,b,c,1

-Author Affiliations

aProgram in Computational Biology and Bioinformatics, Yale University, Bass 426, 266 Whitney Avenue, New Haven, CT 06520; and

bDepartment of Molecular Biophysics and Biochemistry and

cDepartment of Computer Science, Yale University, Bass 432, 266 Whitney Avenue, New Haven, CT 06520

Edited by Peter J. Bickel, University of California, Berkeley, CA, and approved February 10, 2010 (received for review September 21, 2009)


Gene regulatory networks have been shown to share some common aspects with commonplace social governance structures. Thus, we can get some intuition into their organization by arranging them into well-known hierarchical layouts. These hierarchies, in turn, can be placed between the extremes of autocracies, with well-defined levels and clear chains of command, and democracies, without such defined levels and with more co-regulatory partnerships between regulators. In general, the presence of partnerships decreases the variation in information flow amongst nodes within a level, more evenly distributing stress. Here we study various regulatory networks (transcriptional, modification, and phosphorylation) for five diverse species, Escherichia coli to human. We specify three levels of regulators—top, middle, and bottom—which collectively govern the non-regulator targets lying in the lowest fourth level. We define quantities for nodes, levels, and entire networks that measure their degree of collaboration and autocratic vs. democratic character. We show individual regulators have a range of partnership tendencies: Some regulate their targets in combination with other regulators in local instantiations of democratic structure, whereas others regulate mostly in isolation, in more autocratic fashion. Overall, we show that in all networks studied the middle level has the highest collaborative propensity and coregulatory partnerships occur most frequently amongst midlevel regulators, an observation that has parallels in corporate settings where middle managers must interact most to ensure organizational effectiveness. There is, however, one notable difference between networks in different species: The amount of collaborative regulation and democratic character increases markedly with overall genomic complexity.

coregulatory partnerships   hierarchy    middle managers    autocracy   democracy


1To whom correspondence should be addressed.

Author contributions: N.B., K.-K.Y., and M.B.G. designed research; N.B. performed research; K.-K.Y. contributed new reagents/analytic tools; N.B. analyzed data; and N.B. and M.B.G. wrote the paper.
The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

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