title: 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.
authors.affiliation: Howard Hughes Medical Institute, UCLA-DOE Institute for Genomics and Proteomics, Department of Chemistry and Biochemistry, 90095-1570, USA.
authors.forename: Huiying
authors.initials: H
authors.lastname: Li
authors.forename: Matteo
authors.initials: M
authors.lastname: Pellegrini
authors.forename: David
authors.initials: D
authors.lastname: Eisenberg
mesh_terms: D000595:Amino Acid Sequence; D002874:Chromosome Mapping / Q000379:methods*; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation / Q000502:physiology*; D008954:Models, Biological; D008969:Molecular Sequence Data; D025941:Protein Interaction Mapping / Q000379:methods*; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment / Q000379:methods; D020539:Sequence Analysis, Protein / Q000379:methods*; D015398:Signal Transduction / Q000502:physiology*; D013329:Structure-Activity Relationship
chemical_list: D020543:Proteome