Nature Biotechnology
23, 691 - 698 (2005)
Published online: 6 June 2005; | doi:10.1038/nbt1098
Functional genome annotation through phylogenomic mappingBalaji S Srinivasan1, 2, Nora B Caberoy3, Garret Suen3, Rion G Taylor3, Radhika Shah3, Farah Tengra3, Barry S Goldman4, Anthony G Garza3
& Roy D Welch31
Department of Developmental Biology, Stanford University School of Medicine, Stanford, California, USA. 2
Department of Electrical Engineering, Stanford University, Stanford, California. 3
Department of Biology, Syracuse University, 130 College Place, BRL Room 702A, Syracuse, New York 13244-1170, USA. 4
Monsanto Corporation, St. Louis, Missouri, USA.
Correspondence should be addressed to Roy D Welch rowelch@syr.edu All requests for M. xanthus mutants should be made to A.G.G.Accurate determination of functional interactions among proteins at the genome level remains a challenge for genomic research. Here we introduce a genome-scale approach to functional protein annotation—phylogenomic mapping—that requires only sequence data, can be applied equally well to both finished and unfinished genomes, and can be extended beyond single genomes to annotate multiple genomes simultaneously. We have developed and applied it to more than 200 sequenced bacterial genomes. Proteins with similar evolutionary histories were grouped together, placed on a three dimensional map and visualized as a topographical landscape. The resulting phylogenomic maps display thousands of proteins clustered in mountains on the basis of coinheritance, a strong indicator of shared function. In addition to systematic computational validation, we have experimentally confirmed the ability of phylogenomic maps to predict both mutant phenotype and gene function in the delta proteobacterium Myxococcus xanthus.
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