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Domain tree-based analysis of protein architecture evolution
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
2008 (English)In: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 25, no 2, 254-264 p.Article in journal (Refereed) Published
Abstract [en]

Understanding the dynamics behind domain architecture evolution is of great importance to unravel the functions of proteins. Complex architectures have been created throughout evolution by rearrangement and duplication events. An interesting question is how many times a particular architecture has been created, a form of convergent evolution or domain architecture reinvention. Previous studies have approached this issue by comparing architectures found in different species. We wanted to achieve a finer-grained analysis by reconstructing protein architectures on complete domain trees. The prevalence of domain architecture reinvention in 96 genomes was investigated with a novel domain tree-based method that uses maximum parsimony for inferring ancestral protein architectures. Domain architectures were taken from Pfam. To ensure robustness, we applied the method to bootstrap trees and only considered results with strong statistical support. We detected multiple origins for 12.4% of the scored architectures. In a much smaller data set, the subset of completely domain-assigned proteins, the figure was 5.6%. These results indicate that domain architecture reinvention is a much more common phenomenon than previously thought. We also determined which domains are most frequent in multiply created architectures and assessed whether specific functions could be attributed to them. However, no strong functional bias was found in architectures with multiple origins.

Place, publisher, year, edition, pages
2008. Vol. 25, no 2, 254-264 p.
Keyword [en]
protein, domain, architecture, evolution
National Category
Bioinformatics and Systems Biology
Research subject
Biochemistry with Emphasis on Theoretical Chemistry
Identifiers
URN: urn:nbn:se:su:diva-14975DOI: 10.1093/molbev/msm254ISI: 000253634800004PubMedID: 18025066OAI: oai:DiVA.org:su-14975DiVA: diva2:181495
Available from: 2008-11-12 Created: 2008-11-12 Last updated: 2017-12-13Bibliographically approved
In thesis
1. The relationship between orthology, protein domain architecture and protein function
Open this publication in new window or tab >>The relationship between orthology, protein domain architecture and protein function
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Lacking experimental data, protein function is often predicted from evolutionary and protein structure theory. Under the 'domain grammar' hypothesis the function of a protein follows from the domains it encodes. Under the 'orthology conjecture', orthologs, related through species formation, are expected to be more functionally similar than paralogs, which are homologs in the same or different species descended from a gene duplication event. However, these assumptions have not thus far been systematically evaluated.

To test the 'domain grammar' hypothesis, we built models for predicting function from the domain combinations present in a protein, and demonstrated that multi-domain combinations imply functions that the individual domains do not. We also developed a novel gene-tree based method for reconstructing the evolutionary histories of domain architectures, to search for cases of architectures that have arisen multiple times in parallel, and found this to be more common than previously reported.

To test the 'orthology conjecture', we first benchmarked methods for homology inference under the obfuscating influence of low-complexity regions, in order to improve the InParanoid orthology inference algorithm. InParanoid was then used to test the relative conservation of functionally relevant properties between orthologs and paralogs at various evolutionary distances, including intron positions, domain architectures, and Gene Ontology functional annotations.

We found an increased conservation of domain architectures in orthologs relative to paralogs, in support of the 'orthology conjecture' and the 'domain grammar' hypotheses acting in tandem. However, equivalent analysis of Gene Ontology functional conservation yielded spurious results, which may be an artifact of species-specific annotation biases in functional annotation databases. I discuss possible ways of circumventing this bias so the 'orthology conjecture' can be tested more conclusively.

Place, publisher, year, edition, pages
Stockholm: Department of Biochemistry and Biophysics, Stockholm University, 2011. 112 p.
Keyword
homology, orthology, paralogy, gene duplications, protein function prediction, low-complexity regions, protein domains, domain architecture evolution, introns, intron position conservation, orthology conjecture, domain grammar hypothesis
National Category
Bioinformatics and Systems Biology
Research subject
Biochemistry with Emphasis on Theoretical Chemistry
Identifiers
urn:nbn:se:su:diva-62152 (URN)978-91-7447-350-6 (ISBN)
Public defence
2011-10-24, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 14:00 (English)
Opponent
Supervisors
Note
At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 6: Epub ahead of print.Available from: 2011-10-02 Created: 2011-09-09 Last updated: 2011-10-06Bibliographically approved

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