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Detection of evolutionarily stable fragments of cellular pathways by hierarchical clustering of phyletic patterns

BACKGROUND: Phyletic patterns denote the presence and absence of orthologous genes in completely sequenced genomes and are used to infer functional links between genes, on the assumption that genes involved in the same pathway or functional system are co-inherited by the same set of genomes. However...

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Autores principales: Glazko, Galina V, Mushegian, Arcady R
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2004
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC416468/
https://www.ncbi.nlm.nih.gov/pubmed/15128446
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author Glazko, Galina V
Mushegian, Arcady R
author_facet Glazko, Galina V
Mushegian, Arcady R
author_sort Glazko, Galina V
collection PubMed
description BACKGROUND: Phyletic patterns denote the presence and absence of orthologous genes in completely sequenced genomes and are used to infer functional links between genes, on the assumption that genes involved in the same pathway or functional system are co-inherited by the same set of genomes. However, this basic premise has not been quantitatively tested, and the limits of applicability of the phyletic-pattern method remain unknown. RESULTS: We characterized a hierarchy of 3,688 phyletic patterns encompassing more than 5,000 known protein-coding genes from 66 complete microbial genomes, using different distances, clustering algorithms, and measures of cluster quality. The most sensitive set of parameters recovered 223 clusters, each consisting of genes that belong to the same metabolic pathway or functional system. Fifty-six clusters included unexpected genes with plausible functional links to the rest of the cluster. Only a small percentage of known pathways and multiprotein complexes are co-inherited as one cluster; most are split into many clusters, indicating that gene loss and displacement has occurred in the evolution of most pathways. CONCLUSIONS: Phyletic patterns of functionally linked genes are perturbed by differential gains, losses and displacements of orthologous genes in different species, reflecting the high plasticity of microbial genomes. Groups of genes that are co-inherited can, however, be recovered by hierarchical clustering, and may represent elementary functional modules of cellular metabolism. The phyletic patterns approach alone can confidently predict the functional linkages for about 24% of the entire data set.
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spelling pubmed-4164682004-05-22 Detection of evolutionarily stable fragments of cellular pathways by hierarchical clustering of phyletic patterns Glazko, Galina V Mushegian, Arcady R Genome Biol Research BACKGROUND: Phyletic patterns denote the presence and absence of orthologous genes in completely sequenced genomes and are used to infer functional links between genes, on the assumption that genes involved in the same pathway or functional system are co-inherited by the same set of genomes. However, this basic premise has not been quantitatively tested, and the limits of applicability of the phyletic-pattern method remain unknown. RESULTS: We characterized a hierarchy of 3,688 phyletic patterns encompassing more than 5,000 known protein-coding genes from 66 complete microbial genomes, using different distances, clustering algorithms, and measures of cluster quality. The most sensitive set of parameters recovered 223 clusters, each consisting of genes that belong to the same metabolic pathway or functional system. Fifty-six clusters included unexpected genes with plausible functional links to the rest of the cluster. Only a small percentage of known pathways and multiprotein complexes are co-inherited as one cluster; most are split into many clusters, indicating that gene loss and displacement has occurred in the evolution of most pathways. CONCLUSIONS: Phyletic patterns of functionally linked genes are perturbed by differential gains, losses and displacements of orthologous genes in different species, reflecting the high plasticity of microbial genomes. Groups of genes that are co-inherited can, however, be recovered by hierarchical clustering, and may represent elementary functional modules of cellular metabolism. The phyletic patterns approach alone can confidently predict the functional linkages for about 24% of the entire data set. BioMed Central 2004 2004-04-27 /pmc/articles/PMC416468/ /pubmed/15128446 Text en Copyright © 2004 Glazko et al.; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
spellingShingle Research
Glazko, Galina V
Mushegian, Arcady R
Detection of evolutionarily stable fragments of cellular pathways by hierarchical clustering of phyletic patterns
title Detection of evolutionarily stable fragments of cellular pathways by hierarchical clustering of phyletic patterns
title_full Detection of evolutionarily stable fragments of cellular pathways by hierarchical clustering of phyletic patterns
title_fullStr Detection of evolutionarily stable fragments of cellular pathways by hierarchical clustering of phyletic patterns
title_full_unstemmed Detection of evolutionarily stable fragments of cellular pathways by hierarchical clustering of phyletic patterns
title_short Detection of evolutionarily stable fragments of cellular pathways by hierarchical clustering of phyletic patterns
title_sort detection of evolutionarily stable fragments of cellular pathways by hierarchical clustering of phyletic patterns
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC416468/
https://www.ncbi.nlm.nih.gov/pubmed/15128446
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