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Comparative genomic analysis of the DUF71/COG2102 family predicts roles in diphthamide biosynthesis and B12 salvage
BACKGROUND: The availability of over 3000 published genome sequences has enabled the use of comparative genomic approaches to drive the biological function discovery process. Classically, one used to link gene with function by genetic or biochemical approaches, a lengthy process that often took year...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3541065/ https://www.ncbi.nlm.nih.gov/pubmed/23013770 http://dx.doi.org/10.1186/1745-6150-7-32 |
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author | de Crécy-Lagard, Valérie Forouhar, Farhad Brochier-Armanet, Céline Tong, Liang Hunt, John F |
author_facet | de Crécy-Lagard, Valérie Forouhar, Farhad Brochier-Armanet, Céline Tong, Liang Hunt, John F |
author_sort | de Crécy-Lagard, Valérie |
collection | PubMed |
description | BACKGROUND: The availability of over 3000 published genome sequences has enabled the use of comparative genomic approaches to drive the biological function discovery process. Classically, one used to link gene with function by genetic or biochemical approaches, a lengthy process that often took years. Phylogenetic distribution profiles, physical clustering, gene fusion, co-expression profiles, structural information and other genomic or post-genomic derived associations can be now used to make very strong functional hypotheses. Here, we illustrate this shift with the analysis of the DUF71/COG2102 family, a subgroup of the PP-loop ATPase family. RESULTS: The DUF71 family contains at least two subfamilies, one of which was predicted to be the missing diphthine-ammonia ligase (EC 6.3.1.14), Dph6. This enzyme catalyzes the last ATP-dependent step in the synthesis of diphthamide, a complex modification of Elongation Factor 2 that can be ADP-ribosylated by bacterial toxins. Dph6 orthologs are found in nearly all sequenced Archaea and Eucarya, as expected from the distribution of the diphthamide modification. The DUF71 family appears to have originated in the Archaea/Eucarya ancestor and to have been subsequently horizontally transferred to Bacteria. Bacterial DUF71 members likely acquired a different function because the diphthamide modification is absent in this Domain of Life. In-depth investigations suggest that some archaeal and bacterial DUF71 proteins participate in B12 salvage. CONCLUSIONS: This detailed analysis of the DUF71 family members provides an example of the power of integrated data-miming for solving important “missing genes” or “missing function” cases and illustrates the danger of functional annotation of protein families by homology alone. REVIEWERS’ NAMES: This article was reviewed by Arcady Mushegian, Michael Galperin and L. Aravind. |
format | Online Article Text |
id | pubmed-3541065 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-35410652013-01-11 Comparative genomic analysis of the DUF71/COG2102 family predicts roles in diphthamide biosynthesis and B12 salvage de Crécy-Lagard, Valérie Forouhar, Farhad Brochier-Armanet, Céline Tong, Liang Hunt, John F Biol Direct Research BACKGROUND: The availability of over 3000 published genome sequences has enabled the use of comparative genomic approaches to drive the biological function discovery process. Classically, one used to link gene with function by genetic or biochemical approaches, a lengthy process that often took years. Phylogenetic distribution profiles, physical clustering, gene fusion, co-expression profiles, structural information and other genomic or post-genomic derived associations can be now used to make very strong functional hypotheses. Here, we illustrate this shift with the analysis of the DUF71/COG2102 family, a subgroup of the PP-loop ATPase family. RESULTS: The DUF71 family contains at least two subfamilies, one of which was predicted to be the missing diphthine-ammonia ligase (EC 6.3.1.14), Dph6. This enzyme catalyzes the last ATP-dependent step in the synthesis of diphthamide, a complex modification of Elongation Factor 2 that can be ADP-ribosylated by bacterial toxins. Dph6 orthologs are found in nearly all sequenced Archaea and Eucarya, as expected from the distribution of the diphthamide modification. The DUF71 family appears to have originated in the Archaea/Eucarya ancestor and to have been subsequently horizontally transferred to Bacteria. Bacterial DUF71 members likely acquired a different function because the diphthamide modification is absent in this Domain of Life. In-depth investigations suggest that some archaeal and bacterial DUF71 proteins participate in B12 salvage. CONCLUSIONS: This detailed analysis of the DUF71 family members provides an example of the power of integrated data-miming for solving important “missing genes” or “missing function” cases and illustrates the danger of functional annotation of protein families by homology alone. REVIEWERS’ NAMES: This article was reviewed by Arcady Mushegian, Michael Galperin and L. Aravind. BioMed Central 2012-09-26 /pmc/articles/PMC3541065/ /pubmed/23013770 http://dx.doi.org/10.1186/1745-6150-7-32 Text en Copyright ©2012 de Crécy-Lagard et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research de Crécy-Lagard, Valérie Forouhar, Farhad Brochier-Armanet, Céline Tong, Liang Hunt, John F Comparative genomic analysis of the DUF71/COG2102 family predicts roles in diphthamide biosynthesis and B12 salvage |
title | Comparative genomic analysis of the DUF71/COG2102 family predicts roles in diphthamide biosynthesis and B12 salvage |
title_full | Comparative genomic analysis of the DUF71/COG2102 family predicts roles in diphthamide biosynthesis and B12 salvage |
title_fullStr | Comparative genomic analysis of the DUF71/COG2102 family predicts roles in diphthamide biosynthesis and B12 salvage |
title_full_unstemmed | Comparative genomic analysis of the DUF71/COG2102 family predicts roles in diphthamide biosynthesis and B12 salvage |
title_short | Comparative genomic analysis of the DUF71/COG2102 family predicts roles in diphthamide biosynthesis and B12 salvage |
title_sort | comparative genomic analysis of the duf71/cog2102 family predicts roles in diphthamide biosynthesis and b12 salvage |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3541065/ https://www.ncbi.nlm.nih.gov/pubmed/23013770 http://dx.doi.org/10.1186/1745-6150-7-32 |
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