Title |
Resolving the Ortholog Conjecture: Orthologs Tend to Be Weakly, but Significantly, More Similar in Function than Paralogs
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Published in |
PLoS Computational Biology, May 2012
|
DOI | 10.1371/journal.pcbi.1002514 |
Pubmed ID | |
Authors |
Adrian M. Altenhoff, Romain A. Studer, Marc Robinson-Rechavi, Christophe Dessimoz |
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. |
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Geographical breakdown
Country | Count | As % |
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United States | 6 | 20% |
United Kingdom | 4 | 13% |
Sweden | 2 | 7% |
Switzerland | 2 | 7% |
Peru | 1 | 3% |
Canada | 1 | 3% |
France | 1 | 3% |
Luxembourg | 1 | 3% |
Belgium | 1 | 3% |
Other | 1 | 3% |
Unknown | 10 | 33% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 15 | 50% |
Scientists | 12 | 40% |
Science communicators (journalists, bloggers, editors) | 2 | 7% |
Practitioners (doctors, other healthcare professionals) | 1 | 3% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 14 | 4% |
Germany | 4 | 1% |
Brazil | 4 | 1% |
Sweden | 4 | 1% |
Netherlands | 2 | <1% |
Poland | 2 | <1% |
Switzerland | 2 | <1% |
United Kingdom | 2 | <1% |
Canada | 2 | <1% |
Other | 5 | 2% |
Unknown | 282 | 87% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 95 | 29% |
Researcher | 57 | 18% |
Student > Bachelor | 39 | 12% |
Student > Master | 38 | 12% |
Professor | 23 | 7% |
Other | 39 | 12% |
Unknown | 32 | 10% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 169 | 52% |
Biochemistry, Genetics and Molecular Biology | 76 | 24% |
Computer Science | 20 | 6% |
Chemistry | 5 | 2% |
Medicine and Dentistry | 5 | 2% |
Other | 13 | 4% |
Unknown | 35 | 11% |