Resolving the ortholog conjecture: orthologs tend to be weakly, but significantly, more similar in function than paralogs.
Details
State: Public
Version: author
Serval ID
serval:BIB_89CB0AF6A1E2
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Resolving the ortholog conjecture: orthologs tend to be weakly, but significantly, more similar in function than paralogs.
Journal
PLoS Computational Biology
ISSN
1553-7358 (Electronic)
ISSN-L
1553-734X
Publication state
Published
Issued date
2012
Peer-reviewed
Oui
Volume
8
Number
5
Pages
e1002514
Language
english
Abstract
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.
Pubmed
Web of science
Open Access
Yes
Create date
26/03/2012 18:24
Last modification date
20/08/2019 15:48