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Domain architecture conservation in orthologs
Kristoffer Forslund1, Isabella Pekkari, Erik L L Sonnhammer
1Stockholm Bioinformatics Centre, Science for Life Laboratory, Box 1031, Solna, 17121 Sweden.
BMC Bioinformatics
|August 9, 2011
Summary
Orthologous proteins show greater domain architecture conservation than paralogs, supporting their higher functional similarity across species. This highlights the importance of domain arrangement for protein function preservation.
Area of Science:
- Evolutionary Biology
- Bioinformatics
- Genomics
Background:
- Orthologs are crucial for functional annotation transfer due to expected function retention.
- Current ortholog identification methods overlook domain architecture changes, potentially affecting function.
- Domain architecture, the sequential arrangement of protein domains, influences protein function.
Purpose of the Study:
- To assess domain architecture conservation levels among orthologs across diverse species.
- To compare domain architecture conservation between orthologs and paralogs relative to sequence conservation.
- To characterize domain swapping events in orthologs and paralogs.
Main Methods:
- Conducted a large-scale study of domain architecture events between human and 40 other species.
- Developed a score to quantify domain architecture similarity.
- Analyzed differences in conservation between orthologs and paralogs, considering sequence divergence.
Main Results:
- Orthologs demonstrate superior domain architecture conservation compared to paralogs, even at significant sequence divergence.
- Stronger selective pressure likely maintains domain architecture in orthologs for function.
- Insertion/deletion of domains were common changes; domain shuffling and segment duplication/deletion were infrequent.
Conclusions:
- Functional conservation in orthologs is linked to higher domain architecture conservation relative to sequence conservation.
- Results support the hypothesis that orthologs maintain greater functional similarity than other homologs at similar evolutionary distances.
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