Testing the ortholog conjecture with comparative functional genomic data from mammals.

A common assumption in comparative genomics is that orthologous genes share greater functional similarity than do paralogous genes (the "ortholog conjecture"). Many methods used to computationally predict protein function are based on this assumption, even though it is largely untested. He...

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Autores principales:	Nathan L Nehrt, Wyatt T Clark, Predrag Radivojac, Matthew W Hahn
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/1081c89f4e7944239ea8d61ff2938bb7
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spelling	oai:doaj.org-article:1081c89f4e7944239ea8d61ff2938bb72021-11-18T05:50:30ZTesting the ortholog conjecture with comparative functional genomic data from mammals.1553-734X1553-735810.1371/journal.pcbi.1002073https://doaj.org/article/1081c89f4e7944239ea8d61ff2938bb72011-06-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21695233/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358A common assumption in comparative genomics is that orthologous genes share greater functional similarity than do paralogous genes (the "ortholog conjecture"). Many methods used to computationally predict protein function are based on this assumption, even though it is largely untested. Here we present the first large-scale test of the ortholog conjecture using comparative functional genomic data from human and mouse. We use the experimentally derived functions of more than 8,900 genes, as well as an independent microarray dataset, to directly assess our ability to predict function using both orthologs and paralogs. Both datasets show that paralogs are often a much better predictor of function than are orthologs, even at lower sequence identities. Among paralogs, those found within the same species are consistently more functionally similar than those found in a different species. We also find that paralogous pairs residing on the same chromosome are more functionally similar than those on different chromosomes, perhaps due to higher levels of interlocus gene conversion between these pairs. In addition to offering implications for the computational prediction of protein function, our results shed light on the relationship between sequence divergence and functional divergence. We conclude that the most important factor in the evolution of function is not amino acid sequence, but rather the cellular context in which proteins act.Nathan L NehrtWyatt T ClarkPredrag RadivojacMatthew W HahnPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 7, Iss 6, p e1002073 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Nathan L Nehrt Wyatt T Clark Predrag Radivojac Matthew W Hahn Testing the ortholog conjecture with comparative functional genomic data from mammals.
description	A common assumption in comparative genomics is that orthologous genes share greater functional similarity than do paralogous genes (the "ortholog conjecture"). Many methods used to computationally predict protein function are based on this assumption, even though it is largely untested. Here we present the first large-scale test of the ortholog conjecture using comparative functional genomic data from human and mouse. We use the experimentally derived functions of more than 8,900 genes, as well as an independent microarray dataset, to directly assess our ability to predict function using both orthologs and paralogs. Both datasets show that paralogs are often a much better predictor of function than are orthologs, even at lower sequence identities. Among paralogs, those found within the same species are consistently more functionally similar than those found in a different species. We also find that paralogous pairs residing on the same chromosome are more functionally similar than those on different chromosomes, perhaps due to higher levels of interlocus gene conversion between these pairs. In addition to offering implications for the computational prediction of protein function, our results shed light on the relationship between sequence divergence and functional divergence. We conclude that the most important factor in the evolution of function is not amino acid sequence, but rather the cellular context in which proteins act.
format	article
author	Nathan L Nehrt Wyatt T Clark Predrag Radivojac Matthew W Hahn
author_facet	Nathan L Nehrt Wyatt T Clark Predrag Radivojac Matthew W Hahn
author_sort	Nathan L Nehrt
title	Testing the ortholog conjecture with comparative functional genomic data from mammals.
title_short	Testing the ortholog conjecture with comparative functional genomic data from mammals.
title_full	Testing the ortholog conjecture with comparative functional genomic data from mammals.
title_fullStr	Testing the ortholog conjecture with comparative functional genomic data from mammals.
title_full_unstemmed	Testing the ortholog conjecture with comparative functional genomic data from mammals.
title_sort	testing the ortholog conjecture with comparative functional genomic data from mammals.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/1081c89f4e7944239ea8d61ff2938bb7
work_keys_str_mv	AT nathanlnehrt testingtheorthologconjecturewithcomparativefunctionalgenomicdatafrommammals AT wyatttclark testingtheorthologconjecturewithcomparativefunctionalgenomicdatafrommammals AT predragradivojac testingtheorthologconjecturewithcomparativefunctionalgenomicdatafrommammals AT matthewwhahn testingtheorthologconjecturewithcomparativefunctionalgenomicdatafrommammals
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Testing the ortholog conjecture with comparative functional genomic data from mammals.

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