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Domain architecture conservation in orthologs

BACKGROUND: As orthologous proteins are expected to retain function more often than other homologs, they are often used for functional annotation transfer between species. However, ortholog identification methods do not take into account changes in domain architecture, which are likely to modify a p...

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Autores principales: Forslund, Kristoffer, Pekkari, Isabella, Sonnhammer, Erik LL
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3215765/
https://www.ncbi.nlm.nih.gov/pubmed/21819573
http://dx.doi.org/10.1186/1471-2105-12-326
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author Forslund, Kristoffer
Pekkari, Isabella
Sonnhammer, Erik LL
author_facet Forslund, Kristoffer
Pekkari, Isabella
Sonnhammer, Erik LL
author_sort Forslund, Kristoffer
collection PubMed
description BACKGROUND: As orthologous proteins are expected to retain function more often than other homologs, they are often used for functional annotation transfer between species. However, ortholog identification methods do not take into account changes in domain architecture, which are likely to modify a protein's function. By domain architecture we refer to the sequential arrangement of domains along a protein sequence. To assess the level of domain architecture conservation among orthologs, we carried out a large-scale study of such events between human and 40 other species spanning the entire evolutionary range. We designed a score to measure domain architecture similarity and used it to analyze differences in domain architecture conservation between orthologs and paralogs relative to the conservation of primary sequence. We also statistically characterized the extents of different types of domain swapping events across pairs of orthologs and paralogs. RESULTS: The analysis shows that orthologs exhibit greater domain architecture conservation than paralogous homologs, even when differences in average sequence divergence are compensated for, for homologs that have diverged beyond a certain threshold. We interpret this as an indication of a stronger selective pressure on orthologs than paralogs to retain the domain architecture required for the proteins to perform a specific function. In general, orthologs as well as the closest paralogous homologs have very similar domain architectures, even at large evolutionary separation. The most common domain architecture changes observed in both ortholog and paralog pairs involved insertion/deletion of new domains, while domain shuffling and segment duplication/deletion were very infrequent. CONCLUSIONS: On the whole, our results support the hypothesis that function conservation between orthologs demands higher domain architecture conservation than other types of homologs, relative to primary sequence conservation. This supports the notion that orthologs are functionally more similar than other types of homologs at the same evolutionary distance.
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spelling pubmed-32157652011-11-15 Domain architecture conservation in orthologs Forslund, Kristoffer Pekkari, Isabella Sonnhammer, Erik LL BMC Bioinformatics Research Article BACKGROUND: As orthologous proteins are expected to retain function more often than other homologs, they are often used for functional annotation transfer between species. However, ortholog identification methods do not take into account changes in domain architecture, which are likely to modify a protein's function. By domain architecture we refer to the sequential arrangement of domains along a protein sequence. To assess the level of domain architecture conservation among orthologs, we carried out a large-scale study of such events between human and 40 other species spanning the entire evolutionary range. We designed a score to measure domain architecture similarity and used it to analyze differences in domain architecture conservation between orthologs and paralogs relative to the conservation of primary sequence. We also statistically characterized the extents of different types of domain swapping events across pairs of orthologs and paralogs. RESULTS: The analysis shows that orthologs exhibit greater domain architecture conservation than paralogous homologs, even when differences in average sequence divergence are compensated for, for homologs that have diverged beyond a certain threshold. We interpret this as an indication of a stronger selective pressure on orthologs than paralogs to retain the domain architecture required for the proteins to perform a specific function. In general, orthologs as well as the closest paralogous homologs have very similar domain architectures, even at large evolutionary separation. The most common domain architecture changes observed in both ortholog and paralog pairs involved insertion/deletion of new domains, while domain shuffling and segment duplication/deletion were very infrequent. CONCLUSIONS: On the whole, our results support the hypothesis that function conservation between orthologs demands higher domain architecture conservation than other types of homologs, relative to primary sequence conservation. This supports the notion that orthologs are functionally more similar than other types of homologs at the same evolutionary distance. BioMed Central 2011-08-05 /pmc/articles/PMC3215765/ /pubmed/21819573 http://dx.doi.org/10.1186/1471-2105-12-326 Text en Copyright ©2011 Forslund 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 Article
Forslund, Kristoffer
Pekkari, Isabella
Sonnhammer, Erik LL
Domain architecture conservation in orthologs
title Domain architecture conservation in orthologs
title_full Domain architecture conservation in orthologs
title_fullStr Domain architecture conservation in orthologs
title_full_unstemmed Domain architecture conservation in orthologs
title_short Domain architecture conservation in orthologs
title_sort domain architecture conservation in orthologs
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3215765/
https://www.ncbi.nlm.nih.gov/pubmed/21819573
http://dx.doi.org/10.1186/1471-2105-12-326
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