Nature Biotechnology23, 253 - 260 (2005)
Published online: 4 February 2005; | doi:10.1038/nbt1065
Detection of parallel functional modules by comparative analysis of genome sequences
Huiying Li1, Matteo Pellegrini1, 2
& David Eisenberg1
1
Howard Hughes Medical Institute, UCLA-DOE Institute for Genomics and Proteomics, Department of Chemistry and Biochemistry, University of California, Los Angeles, Box 951570, Los Angeles, California 90095-1570, USA.
2
Present address: Rosetta Inpharmatics LLC, a wholly owned subsidiary of Merck & Co., Inc., 401 Terry Ave. N, Seattle, Washington 98109, USA.
Correspondence should be addressed to David Eisenberg david@mbi.ucla.edu
Parallel functional modules are separate sets of proteins in an organism that catalyze the same or similar biochemical reactions but act on different substrates or use different cofactors. They originate by gene duplication during evolution. Parallel functional modules provide versatility and complexity to organisms, and increase cellular flexibility and robustness. We have developed a four-step approach for genome-wide discovery of parallel modules from protein functional linkages. From ten genomes, we identified 37 cellular systems that consist of parallel functional modules. This approach recovers known parallel complexes and pathways, and discovers new ones that conventional homology-based methods did not previously reveal, as illustrated by examples of peptide transporters in Escherichia coli and nitrogenases in Rhodopseudomonas palustris. The approach untangles intertwined functional linkages between parallel functional modules and expands our ability to decode protein functions from genome sequences.
