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Detection of parallel functional modules by comparative analysis of genome sequences

Abstract

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.

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Figure 1: The four-step approach for detecting parallel functional modules.
Figure 2: RNA polymerases display a parallel complex pattern in the clustered genome-wide functional linkage map of D. melanogaster.
Figure 3: The peptide transporters in E. coli K12 display a parallel complex pattern.
Figure 4: The nitrogenases in R. palustris display a parallel functional module pattern.
Figure 5: The functional linkage networks of nitrogenase proteins in R. palustris before and after untangling the parallel functional modules.

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Acknowledgements

We thank Thomas G. Graeber and Michael J. Thompson for helpful discussions and HHMI and Department of Energy for support.

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Correspondence to David Eisenberg.

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Supplementary Fig. 1

Schematic of the Four-Step Approach (PDF 18 kb)

Supplementary Methods (PDF 92 kb)

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Li, H., Pellegrini, M. & Eisenberg, D. Detection of parallel functional modules by comparative analysis of genome sequences. Nat Biotechnol 23, 253–260 (2005). https://doi.org/10.1038/nbt1065

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