Resolving the ortholog conjecture: orthologs tend to be weakly, but significantly, more similar in function than paralogs.

The function of most proteins is not determined experimentally, but is extrapolated from homologs. According to the "ortholog conjecture", or standard model of phylogenomics, protein function changes rapidly after duplication, leading to paralogs with different functions, while orthologs r...

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Autores principales:	Adrian M Altenhoff, Romain A Studer, Marc Robinson-Rechavi, Christophe Dessimoz
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/8bee95db7db04db0a4f3b32bc3922077
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spelling	oai:doaj.org-article:8bee95db7db04db0a4f3b32bc39220772021-11-18T05:51:20ZResolving the ortholog conjecture: orthologs tend to be weakly, but significantly, more similar in function than paralogs.1553-734X1553-735810.1371/journal.pcbi.1002514https://doaj.org/article/8bee95db7db04db0a4f3b32bc39220772012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22615551/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358The function of most proteins is not determined experimentally, but is extrapolated from homologs. According to the "ortholog conjecture", or standard model of phylogenomics, protein function changes rapidly after duplication, leading to paralogs with different functions, while orthologs retain the ancestral function. We report here that a comparison of experimentally supported functional annotations among homologs from 13 genomes mostly supports this model. We show that to analyze GO annotation effectively, several confounding factors need to be controlled: authorship bias, variation of GO term frequency among species, variation of background similarity among species pairs, and propagated annotation bias. After controlling for these biases, we observe that orthologs have generally more similar functional annotations than paralogs. This is especially strong for sub-cellular localization. We observe only a weak decrease in functional similarity with increasing sequence divergence. These findings hold over a large diversity of species; notably orthologs from model organisms such as E. coli, yeast or mouse have conserved function with human proteins.Adrian M AltenhoffRomain A StuderMarc Robinson-RechaviChristophe DessimozPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 8, Iss 5, p e1002514 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Adrian M Altenhoff Romain A Studer Marc Robinson-Rechavi Christophe Dessimoz Resolving the ortholog conjecture: orthologs tend to be weakly, but significantly, more similar in function than paralogs.
description	The function of most proteins is not determined experimentally, but is extrapolated from homologs. According to the "ortholog conjecture", or standard model of phylogenomics, protein function changes rapidly after duplication, leading to paralogs with different functions, while orthologs retain the ancestral function. We report here that a comparison of experimentally supported functional annotations among homologs from 13 genomes mostly supports this model. We show that to analyze GO annotation effectively, several confounding factors need to be controlled: authorship bias, variation of GO term frequency among species, variation of background similarity among species pairs, and propagated annotation bias. After controlling for these biases, we observe that orthologs have generally more similar functional annotations than paralogs. This is especially strong for sub-cellular localization. We observe only a weak decrease in functional similarity with increasing sequence divergence. These findings hold over a large diversity of species; notably orthologs from model organisms such as E. coli, yeast or mouse have conserved function with human proteins.
format	article
author	Adrian M Altenhoff Romain A Studer Marc Robinson-Rechavi Christophe Dessimoz
author_facet	Adrian M Altenhoff Romain A Studer Marc Robinson-Rechavi Christophe Dessimoz
author_sort	Adrian M Altenhoff
title	Resolving the ortholog conjecture: orthologs tend to be weakly, but significantly, more similar in function than paralogs.
title_short	Resolving the ortholog conjecture: orthologs tend to be weakly, but significantly, more similar in function than paralogs.
title_full	Resolving the ortholog conjecture: orthologs tend to be weakly, but significantly, more similar in function than paralogs.
title_fullStr	Resolving the ortholog conjecture: orthologs tend to be weakly, but significantly, more similar in function than paralogs.
title_full_unstemmed	Resolving the ortholog conjecture: orthologs tend to be weakly, but significantly, more similar in function than paralogs.
title_sort	resolving the ortholog conjecture: orthologs tend to be weakly, but significantly, more similar in function than paralogs.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/8bee95db7db04db0a4f3b32bc3922077
work_keys_str_mv	AT adrianmaltenhoff resolvingtheorthologconjectureorthologstendtobeweaklybutsignificantlymoresimilarinfunctionthanparalogs AT romainastuder resolvingtheorthologconjectureorthologstendtobeweaklybutsignificantlymoresimilarinfunctionthanparalogs AT marcrobinsonrechavi resolvingtheorthologconjectureorthologstendtobeweaklybutsignificantlymoresimilarinfunctionthanparalogs AT christophedessimoz resolvingtheorthologconjectureorthologstendtobeweaklybutsignificantlymoresimilarinfunctionthanparalogs
_version_	1718424742886637568

Resolving the ortholog conjecture: orthologs tend to be weakly, but significantly, more similar in function than paralogs.

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