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Sci. Signal., 24 November 2009
Vol. 2, Issue 98, p. ra76
[DOI: 10.1126/scisignal.2000546]

RESEARCH ARTICLES

Eukaryotic Protein Domains as Functional Units of Cellular Evolution

Jing Jin1*, Xueying Xie2{dagger}{ddagger}, Chen Chen1{ddagger}, Jin Gyoon Park1, Chris Stark1§, D. Andrew James1, Marina Olhovsky1, Rune Linding1, Yongyi Mao2*, and Tony Pawson1,3*

1 Centre for Systems Biology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario, Canada M5G 1X5.
2 School of Information Technology and Engineering (SITE), University of Ottawa, Ottawa, Ontario, Canada K1N 6N5.
3 Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada M5S 1A8.

{dagger} Present address: Key Laboratory of Child Development and Learning Science, Ministry of Education, 2 Sipai Lou, Nanjing 210096, China.

{ddagger} These authors contributed equally to this work.

§ Present address: University Health Network Microarray Centre, 101 College Street, Toronto, Ontario, Canada M5G 1L7.

Present address: Cellular and Molecular Logic Team, The Institute of Cancer Research, London SW3 6JB, UK.

Abstract: Modular protein domains are functional units that can be modified through the acquisition of new intrinsic activities or by the formation of novel domain combinations, thereby contributing to the evolution of proteins with new biological properties. Here, we assign proteins to groups with related domain compositions and functional properties, termed "domain clubs," which we use to compare multiple eukaryotic proteomes. This analysis shows that different domain types can take distinct evolutionary trajectories, which correlate with the conservation, gain, expansion, or decay of particular biological processes. Evolutionary jumps are associated with a domain that coordinately acquires a new intrinsic function and enters new domain clubs, thereby providing the modified domain with access to a new cellular microenvironment. We also coordinately analyzed the covalent and noncovalent interactions of different domain types to assess the molecular compartment occupied by each domain. This reveals that specific subsets of domains demarcate particular cellular processes, such as growth factor signaling, chromatin remodeling, apoptotic and inflammatory responses, or vesicular trafficking. We suggest that domains, and the proteins in which they reside, are selected during evolution through reciprocal interactions with protein domains in their local microenvironment. Based on this scheme, we propose a mechanism by which Tudor domains may have evolved to support different modes of epigenetic regulation and suggest a role for the germline group of mammalian Tudor domains in Piwi-regulated RNA biology.

* To whom correspondence should be addressed. E-mail: pawson{at}lunenfeld.ca (T.P.); yymao{at}site.uottawa.ca (Y.M.); jjin{at}lunenfeld.ca (J.J.)

Citation: J. Jin, X. Xie, C. Chen, J. G. Park, C. Stark, D. A. James, M. Olhovsky, R. Linding, Y. Mao, T. Pawson, Eukaryotic Protein Domains as Functional Units of Cellular Evolution. Sci. Signal. 2, ra76 (2009).

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